Featured Studies Open to Enrollment

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Last updated 10/29/2024

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ARREST

Arrest RESpiraTory Failure From Pnemonia

Clinicaltrials.gov

Inclusion Criteria:

Patients 18 years or older with
Severe pneumonia defined as: Hospitalization for acute (defined as ≤ 14 days) onset of symptoms (cough, sputum production, or dyspnea), AND 2. Radiographic evidence of pneumonia by chest radiograph or CT scan, AND 3. One of the following:
- Evidence of systemic inflammation (temperature < 35◦C or > 38◦C OR WBC > or < upper or lower limits for site OR procalcitonin > 0.5 mcg/L), OR
- Known current immunosuppression preventing inflammatory response, OR
- High clinical suspicion of pneumonia with microbiologic confirmation of infection. Microbiologic confirmation will include a positive nasal swab for a known respiratory virus; a sputum culture growing a likely pathogenic organism plus moderate or greater WBCs (not required for immunocompromised patients); or a positive blood culture with a likely pathogenic organism – e.g., ¼ vials with S. Epidermidis would NOT qualify)
- AND Hypoxemia defined as new requirement for daytime supplemental oxygen with SpO2 < 92% on room air, ≤ 96% on ≥ 2 L/min oxygen, or > 6L/min or non-invasive ventilation regardless of SpO2 at enrollment. Patients admitted with pneumonia but not meeting criteria for hypoxemia will be followed for up to 48 hours from ED admission to enrolling hospital to assess for development of qualifying hypoxemia

Exclusion Criteria:

Inability to randomize within 48 hours of presentation to enrolling hospital (randomization beyond 24 hours will be limited to patients with persistent hypoxemia defined by an SpO2 < 97% while on > 3L/min O2)
Intubation (or impending intubation) prior to enrollment
Patients receiving HFNC oxygen or NIV prior to enrollment are not excluded
- A condition requiring inhaled corticosteroids or beta-agonists (patients receiving inhaled beta-agonists in the ED without an established indication will be eligible if treating clinician is willing to discontinue subsequent treatments)
- Chronic systemic steroid therapy equivalent to >10 mg prednisone
- COVID-19 positive patients receiving > 6 mg dexamethasone (40 mg prednisone equivalent dose) except for stress dose steroids for septic shock
- Non-COVID-19 pneumonia patients receiving systemic steroid > 10 mg prednisone except for stress dose steroids for septic shock
- Chronic lung or neuromuscular disease requiring daytime oxygen or mechanical ventilation other than for obstructive sleep apnea (OSA) or obesity hypoventilation syndrome
- Not anticipated to survive > 48 hours or not expected to require > 48 hours of hospitalization
- Contraindication or allergy to inhaled corticosteroids or beta-agonists
- Patients with heart rate > 130 bpm, ventricular tachycardia or new supraventricular tachycardia within last 4 hours will be potentially eligible for enrollment after the condition has resolved
- Patients with K+ < 3.0 will be potentially eligible for enrollment after the condition has resolved
- Patient not committed to full support other than intubation or resuscitation (i.e., DNR/DNI status allowed)
- Pregnancy
- Incarcerated individual
- Physician refusal of consent to protocol
- Patient/surrogate refusal of consent to protocol

FIRST

Food Insecurity Reduction & Strategy Team (FIRST)

clinicaltrials.gov

Inclusion Criteria:

Diagnosis of Type 1 or Type 2 Diabetes Mellitus
Admitted to Stanford Healthcare inpatient unit
Residence in California at time of enrollment
Positive Screening for Food Insecurity
On a Healthcare Plan covered by Mom’s Meals.

Exclusion Criteria:

Plans to be discharged to a skilled nursing facility.
Patients who prefer a language for which a short-form consent is not available.
No Home Address
Pregnant Participants.
No access to refrigerator.

HIT

A Phase 2 Study of VLX-1005 Versus Placebo in Suspected Heparin Induced Thrombocytopenia

clinicaltrials.gov

Inclusion Criteria:

Adult participants ≥ 18 years of age.
Able to provide informed consent or have informed consent provided on their behalf by a primary caregiver prior to study-related activities being initiated.
Recent unfractionated heparin or low-molecular-weight heparin exposure.
Qualifying platelet count < 150 X 10^9/L and clinical 4T score of ≥ 4; candidate for argatroban or bivalirudin treatment.
Positive PF4-immunoassay (eg, ELISA [≥ 1.0 optical density units], LIA [≥ 1.0 U/mL], CLIA [≥ 1.0 U/mL]).

Exclusion Criteria:

Treatment with argatroban or bivalirudin for ≥ 60 hrs prior to randomization.
Following discontinuation of heparin, participants cannot be treated with a non-heparin anti-coagulant for ≥ 60 hours.
Current renal dialysis.
Pregnant or lactating women.
Have participated in any other investigational drug trial within 30 days of dosing or 5 half-lives (whichever is longer) in the current study.
In the opinion of the investigator, unlikely to comply with key elements of the protocol or otherwise inappropriate for the study.

LIBREXIA ACS

A Study of Milvexian in Participants After a Recent Acute Coronary Syndrome (LIBREXIA-ACS)

clinicaltrials.gov

Inclusion Criteria:

Participants must have an index event that meets all 3 of the following criteria within 7 days prior to randomization:
- a) clinical syndrome consistent with spontaneous cardiac ischemia, b) diagnosis of acute coronary syndrome (ACS) (that is, ST-elevation myocardial infarction [STEMI], non-STEMI, or unstable angina [UA]), c) cardiac biomarker elevation (example, troponin I, troponin T, creatine kinase-MB [CK-MB]) above the upper limit of normal as determined by the local laboratory
Participants must have at least 2 of the following risk factors:
- a) age 65 or older, b) diabetes mellitus, c) history of a prior myocardial infarction (MI) (other than index ACS event), d) multivessel coronary artery disease (CAD), e) history of coronary artery bypass graft (CABG) surgery prior to index ACS event, f) history of peripheral artery disease (PAD) or cerebrovascular disease (example, carotid atherosclerosis, intracranial artery stenosis, g) conservative management (that is, no percutaneous intervention [PCI] or CABG after index ACS event), h) Any one or more of the following high-risk angiographic features i) total stent length of greater than (>) 30 millimeters (mm), ii) thrombotic target lesion, iii) bifurcation lesion treated with more than one stent, iv) calcified target lesion treated with atherectomy, v) treatment of obstructive left main or proximal left anterior descending artery for index ACS (or clinical diagnosis of an anterior STEMI)
All female participants of childbearing potential must have a negative highly sensitive serum beta-human chorionic gonadotropin (hCG) or urine test at screening
A female participant must not be pregnant, breastfeeding, or planning to become pregnant until 4 days (5 half-lives) after the last dose of study intervention

Exclusion Criteria:

MI secondary to ischemia due to either increased oxygen demand or decreased supply (Type 2 MI) or periprocedural MI as the index ACS event
Planned CABG or staged PCI after randomization
Any condition that requires chronic anticoagulation at the discretion of the investigator and/or local guidelines
Conditions with a significant increased risk of bleeding (example, clinically significant bleeding within previous 3 months, known bleeding diathesis, et cetera)

LIBREXIA AF

A Study of Milvexian Versus Apixaban in Participants With Atrial Fibrillation (LIBREXIA-AF)

Clinicaltrials.gov

Inclusion Criteria:

Minimum age of 18 years
Medically stable and appropriate for chronic antithrombotic treatment
Atrial fibrillation eligible to receive anticoagulation
Participant must satisfy one or both of the following categories of risk factors (a or b):
- a) one or more of the following risk factors: i) age greater than or equal to 75 years, ii) history of any type of stroke including symptomatic stroke of any kind.
- b) two or more of the following risk factors: i) age between 65 and 74 years, ii) hypertension, iii) diabetes mellitus, iv) atherosclerotic vascular disease, v) heart failure

Exclusion Criteria:

Hemodynamically significant valve disease or those with valve disease that will potentially require surgical valve replacement during the study
Any condition other than AF that requires chronic anticoagulation

LIBREXIA STROKE

A Study of Milvexian in Participants After an Acute Ischemic Stroke or High-Risk Transient Ischemic Attack- (LIBREXIA-STROKE)

Clinicaltrials.gov

Inclusion Criteria:

Ischemic Stroke: a neurological deficit attributable to an acute brain infarction and national institute of health stroke score scale (NIHSS) score less than or equal to (<=) 7 and at least 1 of the following: persistent signs or symptoms of the ischemic event at the time of randomization, or acute, ischemic brain lesion determined by standard-of-care neuroimaging, or participant underwent thrombolysis or thrombectomy, or transient ischemic attack (TIA): acute onset neurological deficit attributable to focal ischemia of the brain by history or examination, with complete symptom resolution of the deficit and no brain infarction on neuroimaging (example, computed tomography (CT) scan or magnetic resonance imaging (MRI), performed as part of standard medical practice), and ABCD2 Score greater than or equal to (>=)
Participants will be randomized as soon as possible after determining eligibility and within 48 hours of onset of event.
Current or planned antiplatelet treatment per international and/or local guidelines. If acetyl salicylic acid (ASA) is used, it will be limited to low dose (75 to 100 milligrams (mg)/day). Loading dose of antiplatelet agents (including ASA) are allowed per standard-of-care
A female participant must agree not to be pregnant, breastfeeding, or planning to become pregnant until 4 days (5 half lives) after the last dose of study intervention
Willing and able to adhere to the lifestyle restrictions specified in this protocol

Exclusion Criteria:

Prior history of intracranial hemorrhage except subarachnoid hemorrhage greater than (>) 1 year prior with adequate treatment
The index stroke or TIA is considered to have a cardio-embolic etiology based on local standard-of-care investigations and for which guidelines recommend anticoagulation
The index stroke or TIA considered to have another known cause, not related to athero-thrombotic sources (treatment of acute stroke trial [TOAST] Other Determined Etiology), based on local standard-of-care investigations
Increased risk of bleeding, including clinically significant bleeding within the previous 3 months or known bleeding diathesis or known activated partial thromboplastin time (aPTT) prolongation or spinal cord hemorrhage or retinal hemorrhage
Current active liver disease, eg, acute hepatitis, known cirrhosis, including participants receiving antiviral treatment for hepatitis
Known allergies, hypersensitivity, or intolerance to milvexian or its excipients

LIMIT Trial

LIMIting AAA with metformin

Clinicaltrials.gov

Inclusion Criteria:

Provision of signed and dated informed consent
Stated willingness to comply with all study procedures and availability for the duration of the study
Male or female, aged 50 to 95 years inclusive
Have a maximal orthogonal infrarenal aortic diameter between 35 and < 50 mm for males and between 30 and < 45 mm for females as measured by CTA
Eligible participants must have an estimated glomerular filtration rate (eGFR) of ≥ 30 ml/min/1.73 m2 at the initiation of trial participation, and must remain ≥ 30 ml/min/1.73 m2 throughout the term of the study to continue participation
HgbA1c must be ≤ 6.5% at initiation to receive study medication
Ability to take oral medication and be willing to adhere to the medication regimen throughout the course of the trial
Must be willing and able to undergo two computed tomographic aortograms (CTA, with timed intravenous iodinated contrast injections if possible) at initiation and termination of study participation
For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening, with an agreement to use such a method of contraception during study participation and for an additional 4 weeks after the end of study drug administration

Exclusion Criteria:

Diagnosis of, or taking medications for, diabetes mellitus, as defined as HgbA1c > 6.5% at baseline evaluation
Known hypersensitivity to metformin hydrochloride. Individuals with known prior anaphylactic reaction to iodinated contrast will have the option of CT scan without contrast or will not be eligible to participate. Individuals with a prior allergic reaction not including anaphylaxis will be managed with the standard CT protocol for premedication for allergy to contrast – 3 doses of prednisone (50 mg p.o. per) beginning 13 hours prior to the procedure as well as 50 mg of Benadryl p.o. Premedication start times are as follows: 13 hours before contrast, 50 mg PO prednisone 7 hours before contrast, 50 mg PO prednisone 1 hour before contrast, 50 mg PO prednisone + 50 mg PO diphenhydramine These individuals will also be given the option of CT scan without contrast if unwilling to follow the premedication as indicated above
Presence of metabolic acidosis, defined as total CO2 below the lower limit of normal on chemistry panel obtained during determination of study eligibility
Expected survival less than two years
Prior surgical AAA repair, or anticipated repair within two years
Known thoracic aortic aneurysm disease, as defined as a prior dissection or thoracic aortic diameter > 5 cm)
The presence of known syndromic aortic conditions, including but not limited to Ehlers Danlos or Marfan Syndromes, or the at-risk allele in the ACTA2 gene mutation or similar conditions
Severe liver disease, jaundice, or active hepatitis
Severe anemia, defined as a Hgb < 10g/dl
Concurrent participation in other investigational drug trials
For female participants of childbearing potential: pregnancy, intent to become pregnant, lactation, or unwilling or unable to use an effective method of contraception
Alcoholism or chronic excessive alcohol intake
Common iliac artery aneurysms > 3.5 cm
Uncontrolled hypertension defined as Systolic BP≥200, or considered to have hypertensive emergency or urgency

POSIBL6ESKD

Combined Dose-Finding and CV Outcomes Study With CSL300 (Clazakizumab) in Adult Subjects With ESKD Undergoing Dialysis. A Phase 2b/3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Combined Dose-Finding and Cardiovascular Outcome Study to Investigate the Efficacy and Safety of CSL300 (Clazakizumab) in Subjects With End Stage Kidney Disease Undergoing Dialysis

Clinicaltrials.gov

Inclusion Criteria:

Male or female at least 18 years of age
A diagnosis of ESKD undergoing maintenance dialysis for at least 12 weeks
Serum hs-CRP ≥ 2.0 mg/L
A diagnosis of diabetes mellitus OR ASCVD
Exclusion Criteria:
Subjects who participated in Part 1 (phase 2b) are not eligible to participate in Part 2 (phase 3)
Concomitant use of systemic immunosuppressant drugs
Abnormal LFTs
Any life-threatening disease expected to result in death within 12 months
A history of GI perforation, inflammatory bowel disease (except fully excised ulcerative colitis), or peptic ulcer disease

REACT-AF

The Rhythm Evaluation for AntiCoagulaTion With Continuous Monitoring of Atrial Fibrillation

Clinicaltrials.gov

Inclusion Criteria:

22-85 years of age
English speaking participants*
History of non-permanent atrial fibrillation
CHA2DS2-VASC score of 1-4 for men and 2-4 for women without prior stroke or TIA**
The participant is on a DOAC at the time of screening and willing to stay on DOAC for duration of study
Willing and able to comply with the protocol, including:
- Possession of a smartwatch-compatible smartphone (iPhone that supports the latest shipping iOS) with a cellular service plan
- Be willing to wear the smartwatch for the suggested minimum of 14 hours a day
- Expected to be within cellular service range at least 80% of the time
- Willing and able to discontinue DOAC
- The participant is willing and able to provide informed consent

Exclusion Criteria:

Valvular or permanent atrial fibrillation
Current treatment with warfarin and unwilling or unable to take a DOAC
The participant is a woman who is pregnant or nursing
The participant is being treated with chronic aspirin, another anti-platelet agent, or chronic NSAIDS outside of current medical guidelines (e.g., primary stroke prevention in patients with atrial fibrillation, primary prevention of cardiovascular events, pain relief, fever, gout) and is unwilling or unable to discontinue use for the study duration
Existing cardiac rhythm device or indication for a permanent pacemaker, ICD or CRT device or planned insertable cardiac monitor. Insertable cardiac monitors are permitted unless they are being used to guide anticoagulation treatment
Known or suspected symptomatic or asymptomatic atrial fibrillation lasting ≥ 1 hour/month over the last 3 months
Any documented single AF episode lasting ≥ 1 hour on standard of care or study-provided external cardiac monitor of > 6 days duration performed within 45 days prior to randomization***
Ablation for AF within last 2 months
Prior or anticipated left atrial appendage occlusion or ligation
Mechanical prosthetic valve(s) or severe valve disease
Hypertrophic cardiomyopathy
Participant needs DOAC for reasons other than preventing stroke or arterial embolism resulting from AF (i.e., preventing DVT or PE) or needs permanent OAC (i.e., congenital heart defects, prosthetic heart valve)
Participants deemed high risk for non-cardioembolic stroke (i.e., significant carotid artery disease defined as stenosis > 75%) based on the investigator’s discretion
The participant is enrolled, has participated within the last 30 days, or is planning to participate in a concurrent drug and/or device study during the course of this clinical trial. Co-enrollment in concurrent trials is only allowed with documented pre-approval from the study manager; there is no concern that co-enrollment could confound the results of this trial
The participant has a tattoo, birthmark, or surgical scar over the dorsal wrist area on the ipsilateral side that the AFSW may be worn
The participant has a tremor on their ipsilateral side that the AFSW may be worn
Any concomitant condition that, in the investigator’s opinion, would not allow safe participation in the study (e.g., drug addiction, alcohol abuse)
Known hypersensitivity or contraindication to direct oral anticoagulants
Documented prior stroke (ischemic or hemorrhagic) or transient ischemic attack
Reversible causes of AF (e.g., cardiac surgery, pulmonary embolism, untreated hyperthyroidism). AF ablation does not constitute reversible AF
> 5% burden of premature atrial or ventricular depolarizations on pre-enrollment cardiac monitoring
History of atrial flutter that has not been treated with ablation (participants in atrial flutter and have been ablated are eligible for enrollment)
Stage 4 or 5 chronic kidney disease
Conditions associated with an increased risk of bleeding:
- Major surgery in the previous month
- Planned surgery or intervention in the next three months that would require cessation of anticoagulation > 2 weeks.
- History of intracranial, intraocular, spinal, retroperitoneal, or atraumatic intra-articular bleeding
- Gastrointestinal hemorrhage within the past year unless the cause has been permanently eliminated (e.g., by surgery)
- Symptomatic or endoscopically documented gastroduodenal ulcer disease in the previous 30 days
- Hemorrhagic disorder or bleeding diathesis
- Need for anticoagulant treatment for disorders other than AF
- Uncontrolled hypertension (SBP >180 mmHg and/or DBP >100 mmHg)

Cell Immune Tolerance (CIT)

54348: Multiple-Low Dose Irradiation, Anti-Thymocyte Globulin and Purified Donor CD34+ and T Cell Transfusion in Living Mismatch Donor Kidney Transplantation

Clinicaltrials.gov

Inclusion Criteria:
• All consenting adults who are 18 to 60 years, living donor transplant candidates and have a haplotype related living donor or > 2 HLA antigen matched, unrelated, living donor (including at least one HLA-DR antigen match plus at least one antigen match of either HLA-A or HLA-B).
• Patients who agree to participate in the study and sign an Informed Consent.
• Patients who have no known contraindication to administration of rabbit ATG or radiation.
• Males and females of reproductive potential who agree to practice a reliable form of contraception for at least 24 months post-transplant.
• ABO compatible.

Exclusion Criteria:
• Previous treatment with rabbit ATG or a known allergy to rabbit proteins.
• History of malignancy with the exception of non-melanoma skin malignancies.
• Pregnant women or nursing mothers.
• Serological evidence of HIV, Hepatitis B or Hepatitis C infection.
• Seronegative for Epstein-Barr virus, if donor is seropositive.
• Leukopenia (with a white blood cell count < 3000/mm3) or thrombocytopenia (with a platelet count < 100,000/mm3).
• Panel Reactive Antibody greater than 80% or demonstration of donor specific antibody (DSA).
• Prior organ transplantation.
• High risk of primary kidney disease recurrence (e.g atypical HUS). However, patients with primary FSGS will not be excluded.

50540 Treg: A Phase I Study of Total Lymphoid Irradiation, Total Body Irradiation, Anti-Thymocyte Globulin and Purified Donor CD34+, T-cell and Recipient T Regulatory Cell Transfusion in Human Leukocyte Antigen Mismatched Living Donor Kidney Transplantation

Clinicaltrials.gov

Inclusion Criteria:
• All consenting adults who are 18 to 65 years, living donor renal transplant recipients at Stanford University Medical Center or Northwestern Medicine who have a haplotype matched (minimum single Human Leukocyte Antigen – DR locus (HLA-DR) and HLA-A or B match) living related or unrelated donor.
• Patients who agree to participate in the study and sign an Informed Consent.
• Patients who have no known contraindication to administration of rabbit ATG or radiation.
• Males and females of reproductive potential who agree to practice a reliable form of contraception for at least 1 year posttransplant

Exclusion Criteria:
• Previous treatment with rabbit ATG or a known allergy to rabbit proteins.
• History of malignancy with the exception of non-melanoma skin malignancies.
• Pregnant women or nursing mothers.
Serological evidence of HIV, Hepatitis B surface antigen positive (HBsAg+), or Hepatitis C infection.
• Epstein Barr Virus (EBV) positive to EBV negative.
• Leukopenia (with a white blood cell count < 3000/mm3) or thrombocytopenia (with a platelet count < 100,000/mm3).
• Panel Reactive Antibody (PRA) greater than 80% or demonstration of historic and/or current donor specific antibody (DSA)
• Prior organ transplantation
• High risk of primary kidney disease recurrence
• Advanced coronary or vascular disease.

46787 STOPT: Total Lymphoid Irradiation, Anti-Thymocyte Globulin and Purified Donor CD34+ and T-cell Transfusion to Withdraw Immunosuppressive Drugs From Recipients of a Previous HLA Matched Living Donor Kidney Transplantation. The Second Chance Study.

Clinicaltrials.gov

Inclusion Criteria:
• All consenting adults of age 18 years and older with previous HLA matched sibling living donor renal transplants who still have their HLA- matched kidney donor available, and who have no history of acute or chronic rejection.
• Patients who agree to participate in the study and sign an Informed Consent
• The HLA-matched donor meets the Stanford Bone Marrow Transplant criteria for stem cell donation, agrees to participate and has signed an Informed Consent.
• The pair is confirmed to be HLA-matched (2 haplo type match) as determined by the histocompatibility laboratory at Stanford.
• Patients who have no known contraindication to the administration of rabbit ATG or radiation
• Males and females of reproductive potential who agree to practice a reliable form of contraception for at least 18 months post transplant.

Exclusion Criteria:
• Known allergy to ATG or a known allergy to rabbit proteins.
History of malignancy with the exception of non-melanoma skin malignancies.
• Pregnant women or nursing mothers.
• Serological evidence of HIV, Hepatitis B (HepBsAg+) or Hepatitis C infection.
• Leukopenia (with a white blood cell count < 3000/mm3) or thrombocytopenia (platelet count < 100,000/mm3)
• Previous history of acute or chronic rejection of the kidney transplant or recurrence of the original disease.
• Screening kidney biopsy demonstrating acute or chronic rejection, recurrence of original disease or interstitial fibrosis/Tubular Atrophy (IF/TA) score greater than 1.

57511 Kidney Deceased Donor: Phase I Study of Combined Deceased Donor Kidney and Hematopoietic Cell Transplants Using a Regimen to Promote Hematopoietic Cell Engraftment

clinicaltrials.gov

Recipient Inclusion Criteria:
1. Patient is ≥ 18 years old, and <65 years of age.
2. Patient has End Stage Renal Disease and is a de novo kidney transplant candidate as part of the Stanford Care team for standard of care.
3. Patient is listed with the Organ Procurement and Transplantation Network (OPTN) for deceased donor transplantation.
4. The recipient has a HLA match with the donor of at least 1 locus in A,B or DR.
5. Males and females of reproductive potential who agree to practice a reliable form of contraception for at least one year post transplantation.
6. Females have a negative serum pregnancy test.
7. The patient has the ability to understand and be willing to sign the written informed consent document. Patients must have a signed informed consent prior to participation on the study.
8. No known contraindication to administration of rabbit ATG or low dose irradiation.

Donor Inclusion Criteria:
1. Brain dead donor aged > 16 and <55.
2. OPO (Organ Procurement Organization) consent for vertebral body procurement.
3. OPO consent for research.
4.Projected cold ischemia time < 24 hours.

Recipient Exclusion Criteria:
1. Known allergy to rabbit protein.
2. History of malignancy with the exception of non-melanoma skin malignancy.
3. Pregnant woman or nursing mother.
4. Body weight > 90kg or BMI > 35.
5. Evidence of HIV 1/2 antibody (ab), HTLV-1 and HTLV-2 Ab, Hepatitis B sAg (Hepatitis B surface antigen). Hepatitis C Ab, or positive syphilis screen.
6. EBV Ab-positive donor to EBV Ab-negative recipient.
7. Active bacterial, viral or fungal infection defined as currently taking medication for the infection.
8. Leukopenia, (white blood cell count < 3000/mm3) or thrombocytopenia (with a platelet count < 100,000/mm3).
9. Psychiatric disorder(s) or psycho-social circumstance(s) which in the opinion of the Stanford Transplant team caring for this potential patient would place the patient at an unacceptable risk.
10. Concern for alcohol or other substance abuse.
11. Kidney disease at high risk for post-transplant recurrence: aHUS (atypical hemolytic – uremic syndrome) and C3 glomerulopathy.
12. Panel reactive antibody (PRA) >80%.
13. Positive donor specific antibody (DSA).
14. Prior or combined organ transplant.
15 Patients with >5 pack year smoking history, smoking within 10 years of enrollment, or first degree relative with lung cancer

58350 SPIRIT: Clinical Islet Transplantation with Apheresis, Isolation and Reintroduction of Recipient Regulatory T cells or Administration of Deceased Donor Vertebral Bone Marrow in Type 1 Diabetes

Clinicaltrials.gov

Inclusion Criteria:
• Male and female patients age 18 to 70 years of age.
• Ability to provide written informed consent.
• Mentally stable and able to comply with the procedures of the study protocol.
• Clinical history compatible with T1D with onset of disease at < 45 years of age, insulin- dependence for ≥ 5 years at the time of enrollment, or a sum of patient age and insulin dependent diabetes duration of ≥ 28.
• Absence of stimulated C peptide (< 0.3 ng/mL) in response to a mixed meal tolerance test measured at 60 and 90 minutes after the start of consumption
• Involvement in intensive diabetes management defined as self-monitoring of glucose values no less than a mean of three times each day averaged over each week and by the administration of three or more insulin injections each day or insulin pump therapy. Such management must be under the direction of an endocrinologist, diabetologist, or diabetes specialist with at least 3 clinical evaluations during the 12 months prior to study enrollment.
• At least two episodes of severe hypoglycemia in the 12 months prior to study enrollment.
• Reduced awareness of hypoglycemia as defined by a Clarke score of 4 or more OR a HYPO score greater than or equal to the 90th percentile (1047) during the screening period and within the last 6 months prior to randomization.
• Women of childbearing potential may be enrolled if a pregnancy test is negative, and they agree to the use of 2 forms of contraception from Screening to the end of the study. Males must agree to use 2 forms of contraception from Screening to the end of the study if their partners are of childbearing potential.
• Acceptable methods of birth control which must be used together are:
• Oral contraceptive and condom (combination oral contraceptives containing the second- generation progestin (levonorgestrel) and <30 μg of estrogen should be utilized),
IUD and condom,
• Diaphragm with spermicide and condom
• Subject must complete training on how to use the Tandem X2 pump with Control IQ technology by a certified Diabetes Educator or physician. Patients must complete at least 2 hour training to the satisfaction of the educator and show proficiency and understanding in its use as judged by the educator.
• Patients with prior kidney transplantation on immunosuppressive medications are eligible provided they meet all eligibility criteria above excluding the need for hypoglycemia unawareness. Patients should not be candidates for solid organ pancreas transplant or have declined the surgical option.

Exclusion Criteria:
• Body mass index (BMI) >30 kg/m2 or patient weight ≤50kg.
Insulin requirement of >1.0 IU/kg/day or <15 U/day. 3. HbA1c >10%.
• Treatment with any anti-diabetic medication other than insulin within 4 weeks of Screening
• Untreated proliferative diabetic retinopathy.
• Blood Pressure: SBP >180 mmHg or DBP >100 mmHg on optimal treatment.
• Estimated glomerular filtration rate of <50 mL/min/1.73m2.
• Presence or history of macroalbuminuria (>500mg/g creatinine).
• Presence or history of panel-reactive anti-HLA antibodies >50%. Negative cross- match by flow cytometry and no DSA to organ donor by standard methods.
• For female subjects: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study and 4 months after discontinuation.
• For male participants: intent to procreate during the duration of the study or within 4 months after discontinuation or unwillingness to use effective measures of contraception
• Presence of active infection including hepatitis B, hepatitis C, HIV, or tuberculosis (TB). Subjects with laboratory evidence of active infection are excluded even in the absence of clinical evidence of active infection.
• Negative screen for Epstein-Barr Virus (EBV) by IgG determination.
• Invasive aspergillus, histoplasmosis, or coccidioidomycosis infection within one year prior to study enrollment.
• Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin.
• Known active alcohol or substance abuse.
• Baseline Hb below the lower limits of normal; neutropenia (<1,500/7L), or thrombocytopenia (platelets <100,000/7L).
• Any coagulopathy or medical condition requiring long-term anticoagulant therapy (e.g., warfarin) after islet transplantation (low-dose aspirin treatment is allowed) or patients with an international normalized ratio (INR) >1.5.
• Severe co-existing cardiac disease, characterized by any one of these conditions:recent myocardial infarction (within past 6 months).
• evidence of uncorrectable ischemia on functional cardiac exam within the last year.
• left ventricular ejection fraction <30%.
• Persistent elevation of liver function tests at the time of study entry.
• Persistent serum glutamic-oxaloacetic transaminase (SGOT [AST]), serum glutamate pyruvate transaminase (SGPT [ALT]), or total bilirubin, with values > 1.5 times normal upper limits will exclude a patient.
• Acute or chronic pancreatitis.
• Treatment with any anti-diabetic medication other than insulin within 4 weeks of enrollment.
• Use of any investigational agents within 4 or more weeks of enrollment, depending upon the pharmacokinetics of the investigational agent and durability of changes with treatment in immune function or glycemic regulation.
• Administration of live attenuated vaccine(s) within 2 months of enrollment.
• Any medical condition that, in the opinion of the investigator, will interfere with safe participation in the trial.
• A previous islet transplant.
• History of medical non-adherence or poor social support.
• Individuals with selective IgA deficiencies (IgA level less than 15 mg/dL) who have known antibody against IgA.

Biobanking Protocol: Biobanking of blood components, bone marrow, and other research samples for Cellular Immune Tolerance Program

clinicaltrials.gov – N/A

Inclusion Criteria:
• Adult study participant, > 18 years of age, who signed informed consent to participate in a CIT DFG clinical trial of cell therapy for non-malignant diseases and/or organ transplant tolerance study.

Exclusion Criteria:
• None

KYSA-1 Kyverna Lupus Nephritis – Industry: A Phase 1, Open-Label, Multicenter Study of KYV-101, an Autologous Fully-Human Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects with Refractory Lupus Nephritis

clinicaltrials.gov

Inclusion Criteria:
• Age ≥18 years
• Clinical diagnosis of SLE according to 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria
• Biopsy-proven proliferative LN Class III or IV according to 2018 International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria
• Positive anti-nuclear antibody (ANA) (titer ≥1:80 ), anti-dsDNA (≥30 IU/mL on enzyme-linked immunosorbent assay [ELISA]), or anti-Smith at screening or by documented medical history
• Up to date on recommended vaccinations, including against coronavirus disease 2019 (COVID-19)/ severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), per Centers for Disease Control and Prevention (CDC) or institutional guidelines for immune compromised individuals

Exclusion Criteria:
• Rapidly progressive glomerulonephritis; history of or currently active severe central nervous system (CNS) lupus, including cerebritis, cerebrovascular accident, and seizures
• Prior treatment with cellular immunotherapy (CAR-T) or gene therapy product directed at any target
• History of allogeneic or autologous stem cell transplant
• Evidence of active hepatitis B or hepatitis C infection
• Positive serology for HIV
• Primary immunodeficiency
• History of splenectomy
• History of stroke, seizure, dementia, Parkinson’s disease, coordination movement disorder, cerebellar diseases, psychosis, paresis, aphasia, and any other neurologic disorder investigator considers would increase the risk for the subject
• Impaired cardiac function or clinically significant cardiac disease
• Previous or concurrent malignancy with the following exceptions: 1. Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to screening), 2. In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to screening, 3. A primary malignancy which has been completely resected, or treated, and is in complete remission for at least 5 years prior to screening

Kyverna Multiple Sclerosis Phase 1 – IIT: A Phase 1, Open-Label, Single Center Study of KYV-101, an Autologous Fully-Human Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects with Non-relapsing and Progressive Forms of Multiple Sclerosis

clinicaltrials.gov

Inclusion Criteria:
• Prior treatment with anti-CD20+ monoclonal antibody therapy within 9 months of trial initiation. A 30-day washout will be required for prior treatment with glatiramer acetate, interferon-beta, and fumarates. A 60-day washout will be required for sphingosine-i-phosphate modulators and natalizumab. Excluded will be patients who received prior treatment with mitoxantrone regardless of prior cumulative dose.
• Prior history of solid organ transplantation
• Impaired cardiac function or clinically significant cardiac disease including:
o a. Unstable angina or myocardial infarction or coronary artery bypass graft (CABG) within 6 months prior to apheresis.
o b. New York Heart Association (NYHA) stage III or IV congestive heart failure.
o c. History of clinically significant cardiac arrhythmia (eg, ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block.
o d. History of severe nonischemic cardiomyopathy.
o e. Left ventricular ejection fraction (LVEF) <45% as assessed by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan (performed ≤8 weeks of apheresis).
o f. Active, current cardiac manifestations of systemic lupus erythematosus (SLE) including pericarditis, pericardial effusion, and myocarditis.
• Prior history of splenectomy
• History of moderate or worse than moderate asthma or chronic obstructive pulmonary disease (COPD)
• Corrected QT interval (QTc) >450msec in males or >470msecs in females
• Subjects with valvular heart disease (regurgitation, stenosis or atresia
• Moderate or worse renal impairment using criteria
a. Stage 1: Kidney damage with normal or increased GFR (>90 mL/min/1.73 m^2).
b. Stage 2: Mild reduction in GFR (60-89 mL/min/1.73 m^2).
c. Stage 3a: Moderate reduction in GFR (45-59 mL/min/1.73 m^2).
d. Stage 3b: Moderate reduction in GFR (30-44 mL/min/1.73 m^2).
e. Stage 4: Severe reduction in GFR (15-29 mL/min/1.73 m^2).
f. Stage 5: Kidney failure (GFR < 15 mL/min/1.73 m^2 or dialysis)
• Previously received Mavenclad, yet drug washout is ≤9 months.
• History of a seizure disorder even if the seizure disorder is well controlled with anti-epileptics
• Prior history of treatment with cellular immunotherapy (e.g. CAR T) gene therapy product directed as any target.

Kyverna Dermatomyositis – IIT: A Phase 1B, Open-Label, Single Center Study of KYV 101, an Autologous Fully-Human Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Adult Patients with treatment refractory Dermatomyositis

clinicaltrials.gov

Exclusion Criteria:
• Rapidly progressive glomerulonephritis; history of or currently active severe central nervous system (CNS) lupus, including cerebritis, cerebrovascular accident, and seizures
• Prior treatment with cellular immunotherapy (CAR-T) or gene therapy product directed at any target
• History of allogeneic or autologous stem cell transplant
• Evidence of active hepatitis B or hepatitis C infection
• Positive serology for HIV
• Primary immunodeficiency
• History of splenectomy
• History of stroke, seizure, dementia, Parkinson’s disease, coordination movement disorder, cerebellar diseases, psychosis, paresis, aphasia, and any other neurologic disorder investigator considers would increase the risk for the subject
• Impaired cardiac function or clinically significant cardiac disease
• Previous or concurrent malignancy with the following exceptions:
• Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to screening)In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to screening

Sonoma Rheumatoid Arthritis – Industry: A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Activity of Single Ascending Doses of SBT777101 in Subjects with Rheumatoid Arthritis.

clinicaltrials.gov

Inclusion Criteria:
• Body mass index (BMI) <35 kg/m^2, inclusive
Adult-onset, moderate-to-severe rheumatoid arthritis (RA)
• Moderate-to-severe active disease
• Clinical and/or ultrasound evidence of synovitis
• Prior inadequate response to or unable to tolerate available RA therapies
• Stable doses of RA medications for at least 30 days
• Use of highly effective methods of contraception

Exclusion Criteria:
• Major surgery within 12 weeks prior to screening or planned within 12 months after dosing
• Uncontrolled cardiovascular, pulmonary, renal, hepatic, endocrine, or gastrointestinal disease
• Recurrent infections or active infection
• Active or untreated latent tuberculosis
• Primary or secondary immunodeficiency
• History of or current inflammatory joint disease other than RA

KYSA-5 Kyverna Scleroderma – Industry: A Phase 1/2, Open-Label, Multicentre Study of KYV-101, an Autologous Fully Human Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects with Systemic Sclerosis (KYSA-5)

clinicaltrials.gov

Exclusion Criteria:
• Rapidly progressive glomerulonephritis; history of or currently active severe central nervous system (CNS) lupus, including cerebritis, cerebrovascular accident, and seizures
• Prior treatment with cellular immunotherapy (CAR-T) or gene therapy product directed at any target
• History of allogeneic or autologous stem cell transplant
• Evidence of active hepatitis B or hepatitis C infection
• Positive serology for HIV
• Primary immunodeficiency
• History of splenectomy
• History of stroke, seizure, dementia, Parkinson’s disease, coordination movement disorder, cerebellar diseases, psychosis, paresis, aphasia, and any other neurologic disorder investigator considers would increase the risk for the subject
• Impaired cardiac function or clinically significant cardiac disease
• Previous or concurrent malignancy with the following exceptions:
• Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to screening)
• In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to screening

KYSA-6 Kyverna Myasthenia Gravis – Industry: A Phase 2, Open-Label, Multicentre Study of KYV 101, an Autologous Fully Human Anti-CD19 Chimeric Antigen Receptor T Cell (CD19 CAR T) Therapy, in Subjects with Refractory Generalized Myasthenia Gravis (KYSA-6)

clinicaltrials.gov

Key Inclusion Criteria:
• Diagnosis of MG with presence of autoantibodies to AChR and MuSK
• Myasthenia Gravis Foundation of America (MGFA) Class IIB-IV*
• MG-Activities of Daily Living (MG-ADL) total score of ≥6 at screening and at pre-dose baseline
• Failed treatment over 1 year or more with 2 or more immunosuppressive/immunomodulatory therapies or; failed at least 1 immunosuppressive therapy and required chronic plasmapheresis, or IVIG to control symptoms**
• On a stable dose of glucocorticoids and/or other immunotherapies for ≥1 month prior to screening. For azathioprine, being on a stable dose for ≥2 months prior to screening is require
• No change in dose of acetylcholinesterase inhibitors for ≥2 weeks prior to screening
• No use of IV Igor plasma exchange (PLEX) within 4 weeks of pre-dose baseline
• (*) For Germany Sites: Myasthenia Gravis Foundation of America (MGFA) Class III-IV. Patients with disease classified as MGFA Class IIB may be included if the patient requires continuous treatment with IVIG or PLEX to be maintained at MGFA class IIB.
• (**) For Germany Sites: In the preceding 2 years failed two monoclonal antibodies with different mechanisms of action – or – failed at least 1 monoclonal antibody and required chronic plasmapheresis, or IVIg to control symptoms. Patients are required to have failed two different monoclonal antibodies as treatment for the preceding 1 to 2 years.

Key Exclusion Criteria:
• Impaired cardiac function or clinically significant cardiac disease including: Unstable angina or myocardial infarction or coronary artery bypass graft within 6 months prior to apheresis New York Heart Association stage III or IV congestive heart failure, History of clinically significant cardiac arrhythmia (e.g., ventricular tachycardia, QTc prolongation, and/or torsades de pointes), complete left bundle branch block, high-grade atrioventricular block,
History of severe nonischaemic cardiomyopathy, Left ventricular ejection fraction (LVEF) <45% as assessed by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan (performed ≤8 weeks of apheresis)
Serious and/or uncontrolled medical condition and severity of the underlying MG disease activity that, in the investigator’s judgment, would cause unacceptable safety risk, interfere with study procedures or results, or compromise compliance with the protocol, such as:
• Active, uncontrolled, viral, bacterial, or systemic fungal infection (including human T -cell lymphotropic virus [HTLV], human polyomavirus 2 [JC virus], or syphilis); or recent history of repeated infections
• Clinical evidence of dementia or altered mental status
Recent thromboembolic event
• On anti-coagulation agents that would be unsafe to transiently hold for medical procedures

KYSA-7 Kyverna Multiple Sclerosis Phase 2 – Industry: A Phase 2, Open-Label, Randomized, Multicenter Study of KYV-101, an Autologous Fully Human Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects with Refractory Primary and Secondary Progressive Multiple Sclerosis (KYSA-7) (GENE TRANSFER)

clinicaltrials.gov

Inclusion Criteria:
• Patient is ≥ 18 years old, and ≤65 years of age, at time of screening visit.
• Diagnosis of MS according to the 2017 McDonald Criteria.
• Progressive MS by 2014 Lublin MS phenotypic criteria.
• Presence of varicella-zoster virus (VZV) antibodies, or completion of at least one dose of the varicella zoster glycoprotein E (gE) Shingrix vaccine at least four weeks prior to treatment.
• Presence of anti EBV antibodies.
• Organ and Marrow Function
• Absolute neutrophil count (ANC) ≥ 2000/uL.
• Platelet count ≥ 150,000/uL.
• Absolute lymphocyte count ≥ 1000/uL.
• Serum immunoglobulin G (IgG) ≥ 500mg/dL.
• Hemoglobin ≥ 9 g/dL.
• Adequate renal, hepatic, pulmonary and cardiac function defined as: Creatinine ≤ 2mg/dL or creatinine clearance (as estimated by Cockcroft Gault Equation) ≥ 60 mL/min, Serum alanine transaminase (ALT)/aspartate aminotransferase (AST) ≤ 3 upper limit of normal (ULN), Total bilirubin ≤ 1.5 mg/dl, except in subjects with Gilbert’s syndrome, Cardiac ejection fraction ≥ 40%, no evidence of physiologically significant pericardial effusion as determined by an ECHO, and no clinically significant ECG findings, Baseline oxygen saturation > 94% on room air.
• Testing for Hepatitis B core antibody (HBc Ab), Hepatitis C antibody (HCV Ab), Hepatitis B surface antigen (Hep B surf. AG), HIV 1&2 Ab, Syphilis Screen, Human T-cell lymphotropic virus (HTLV) Ab I & II, Nucleic acid test multiplex (NAT MPX) for HIV, HCV, HBV, Herpes Simplex Virus 1 & 2 IgG panel, Varicella-Zoster (VZ) IgG, Cytomegalovirus (CMV) Total Ab, Must be seronegative for HIV-1 RNA polymerase chain reaction (PCR); HIV 1 and HIV 2 Ab (antibody); HTLV-1 and HTLV-2 Ab; PCR+ or negative surface antigen for hepatitis B; negative for the Treponema pallidum antibody Syphilis screen; and negative for HIV-1 and hepatitis C by nucleic acid testing (NAT) within 40 days of apheresis procedures.
• Females of childbearing potential have a negative serum or urine pregnancy test because of the potentially dangerous/unknown effects on the fetus. Females who have undergone hysterectomy or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential.
• Contraception: Subjects of child-bearing or child-fathering potential must be willing to practice highly effective birth control from the time of enrollment on this study and for the entire study period which is 12 months after receiving the CAR T cell infusion.
• Ability to understand and the willingness to sign a written informed consent document. Patients must have signed informed consent to participate in the trial.
• Adequate vital sign criterion with acceptable numerical ranges of: Systolic Blood Pressure (mmHg) ≥ 100 and ≤ 150, Diastolic Blood pressure (mmHg) ≥ 60 and ≤ 90, To ensure subject safety and stability, any subject who is noted to have a BP > 150/90 mm Hg should be stable on anti-hypertensive medications with repeated BP ≤150/90 for at least one month prior to enrollment in the study
• Heart Rate ≥ 60 and ≤ 100 bpm
• Oral Temperature ≤ 37.7 C/afebrile
• Respiratory rate ≥ 12 and ≤ 20bpm

Exclusion Criteria:
• History of neuromyelitis optica spectrum disorder (NMOSD) or MOG antibody associated disease (MOGAD).
• Prior treatment with any investigational agent within 3 months, or 5 half-lives, whichever is longer. Agents authorized by the FDA for prevention or treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not considered investigational.
• Initiation of any DMT between the completion of apheresis and start of lymphodepletion (LD) chemotherapy. The use of methylprednisolone for bridging therapy between apheresis and start of LD chemotherapy will be allowed.
• History of CNS or spinal cord tumor, metabolic or infectious cause of myelopathy, genetically inherited progressive CNS disorder, sarcoidosis or non-MS progressive neurologic condition affecting ability to perform study assessments.
• History of cytopenia consistent with the diagnosis of myelodysplastic syndrome (MDS).
• History of sickle cell anemia or other hemoglobinopathy.
• Coagulation abnormalities defined by: international normalized ratio (INR) > 1.5, prothrombin time (PT) > 14 seconds, partial thromboplastin time (PTT) > 45 seconds to the exclusion criteria. Patients with positive antiphospholipid antibodies, including anti-cardiolipin, or lupus anticoagulant.
• Presence of fungal, bacterial, viral, or other infection that is not controlled and/ or requiring hospitalization or treatment with IV antimicrobials within 4 weeks of screening. Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
• Psychiatric disorder(s) or psychosocial circumstance(s) which in the opinion of the Stanford Transplant team caring for this potential patient would place the patient at an unacceptable risk.
• Presence or history of liver cirrhosis.
• History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 3 years
• Active infection with HIV, hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive) as the immunosuppression contained in this study may pose unacceptable risk. A prior history of hepatitis B or hepatitis C is permitted providing the viral load is undetectable per quantitative PCR and/or nucleic acid testing. Hepatitis B surface antibody following hepatitis B immunization is not considered to be evidence of past infection.
• Central nervous system (CNS) disorder such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease unrelated to MS that in the judgment of the investigator may impair the ability to evaluate neurotoxicity.
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease (uncontrolled congestive heart failure) within 4 months of enrollment. Subjects with stable cardiac disease fulfilling inclusion criteria are allowed.
• Subjects receiving anticoagulation therapy or subjects with concomitant use of antiplatelet agents.
• History of Crohn’s, rheumatoid arthritis, systemic lupus that required continued systemic immunosuppression/systemic disease modifying agents within the 2 years prior to trial enrollment.
• A primary immune deficiency disease
• In the investigator’s judgment, the subject is unlikely to complete protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.
• History of severe immediate hypersensitivity reaction to any of the agents used in this study. This includes contraindications or life-threatening allergies, hypersensitivity, or intolerance to KYV-101 or its excipients, including dimethyl sulfoxide; Bendamustine; or tocilizumab.
• Any medical condition that in the judgement of the investigator is likely to interfere with assessment of safety or efficacy of study treatment.
• Prior treatment with total lymphoid irradiation or mitoxantrone exceeding 36 mg/m2 cumulative dose
• Prior treatment with autologous hematopoietic stem cell transplantation, or prior history of cellular immunotherapy (eg. CAR T) or gene therapy directed at any target.
• Prior treatment with anti-CD20+ monoclonal antibody therapy within 9 months of trial initiation. A 30-day washout will be required for prior treatment with glatiramer acetate, interferon-beta, and fumarates. A 60-day washout will be required for sphingosine-i-phosphate modulators and natalizumab. Excluded will be patients who received prior treatment with mitoxantrone regardless of prior cumulative dose.
• Prior history of solid organ transplantation
• Impaired cardiac function or clinically significant cardiac disease including:

1. Unstable angina or myocardial infarction or coronary artery bypass graft (CABG) within 6 months prior to apheresis.
2. New York Heart Association (NYHA) stage III or IV congestive heart failure.
3. History of clinically significant cardiac arrhythmia (eg, ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block.
4. History of severe nonischemic cardiomyopathy.
5. Left ventricular ejection fraction (LVEF) <45% as assessed by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan (performed ≤8 weeks of apheresis).
6. Active, current cardiac manifestations of systemic lupus erythematosus (SLE) including pericarditis, pericardial effusion, and myocarditis.Impaired cardiac function or clinically significant cardiac disease including:Prior history of splenectomyHistory of moderate or worse than moderate asthma or chronic obstructive pulmonary disease (COPD)
• Corrected QT interval (QTc) >450msec in males or >470msecs in females
• Subjects with valvular heart disease (regurgitation, stenosis or atresia
• Moderate or worse renal impairment using criteria
• Stage 1: Kidney damage with normal or increased GFR (>90 mL/min/1.73 m^2).
• Stage 2: Mild reduction in GFR (60-89 mL/min/1.73 m^2).
• Stage 3a: Moderate reduction in GFR (45-59 mL/min/1.73 m^2).
• Stage 3b: Moderate reduction in GFR (30-44 mL/min/1.73 m^2).
• Stage 4: Severe reduction in GFR (15-29 mL/min/1.73 m^2).
• Stage 5: Kidney failure (GFR < 15 mL/min/1.73 m^2 or dialysis)
• Previously received Mavenclad, yet drug washout is ≤9 months.
• History of a seizure disorder even if the seizure disorder is well controlled with anti-epileptics
• Prior history of treatment with cellular immunotherapy (e.g. CAR T) gene therapy product directed as any target.

Sonoma Hidradenitis Suppurativa: A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Activity of Single Ascending Doses of SBT777101 in Subjects with Hidradenitis Suppurativa

Clinicaltrials.gov

Inclusion Criteria:

Participant with a history of signs and symptoms consistent with HS for at least 1 year prior to baseline.
Participant must have HS lesions present in at least 2 distinct anatomic areas, one of which must be Hurley Stage II or Hurley Stage III.
Participant must have had an inadequate response to at least a 3-month treatment of an oral antibiotic for treatment of HS as assessed by the Investigator.
Participant must have a total AN count of ≥5 at the baseline visit.
Participant must have a draining tunnel count of ≤20 at the baseline visit.
Participant must have a CRP >3 mg/L obtained at screening.
Participant must be willing and able to complete the diary for the duration of the study as required by the study protocol.
Contraceptive use by men with a partner of childbearing potential and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion Criteria:

Participant with any other active skin disease or condition (eg, bacterial, fungal, or viral infection) that may interfere with assessment of HS.
Any active or chronic infection requiring systemic treatment (eg, antibiotics, antivirals, antifungals, antihelminthics) within 30 days prior to baseline.
Known history of or suspected significant suppressed immune response, including history of invasive opportunistic or helminthic infections despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged duration.
Participant with history of solid organ transplant.
Participant with history of splenectomy.
Participant with history of any malignancy or lymphoproliferative disease, except if the participant has been free from disease for ≥5 years. Successfully treated non-metastatic cutaneous squamous cell carcinoma, basal cell carcinoma, or localized carcinoma in situ of the cervix are allowed.
Participant with a diagnosis of chronic immune-mediated, inflammatory conditions other than HS
Participant with family history of sudden death or long QT syndrome.
Participant with history of congenital or drug-induced long QT syndrome.
Participant with congestive heart failure (New York Heart Association Class 2 to 4), greater than Class 1 angina pectoris, acute coronary syndrome within prior 6 months, known structural heart disease.
Participant with history of any major cardiovascular events (eg, myocardial infarction, unstable angina pectoris, coronary revascularization, stroke, or transient ischemic attack) at any time prior to screening.
Participant with history of ventricular fibrillation, ventricular tachycardia, torsades de pointes, atrial fibrillation, syncope not explained by non-cardiac etiology.
Participant with uncontrolled hypertension defined as consistent systolic blood pressure ≥150 mmHg or consistent diastolic blood pressure ≥90 mmHg despite antihypertensive medication.
Participant received prescription topical therapies for the treatment of HS within 14 days prior to the baseline visit.
Prior or active treatment with any systemic biologic (anti-TNF) therapy, anti-IL17 therapy, anti-IL1/anti-IL1 receptor therapy except for up to 20% of the total study population. Furthermore, this 20% of biologic-experienced participants must fulfilled one or more of the following conditions:
- Discontinued due to treatment related toxicity and/or
- Discontinuation is not related to lack or loss of therapeutic response.

The above information is not intended to contain all considerations relevant to a participant’s potential participation in a clinical trial.

Abata Multiple Sclerosis: A Phase 1 open-label, single ascending dose study of ABA-101 in participants with progressive multiple sclerosis

Clinicaltrials.gov

Inclusion criteria:

Male or female adult with a diagnosis of progressive multiple sclerosis (MS) including primary progressive MS, secondary progressive MS, or progressive relapsing MS.
Aged between 18 and 65 years, inclusive.
Body weight greater than 40.0 kg.
Female patients of child bearing potential must use 2 highly effective contraception methods.
Male patients, whose partners are of childbearing potential (including lactating women), must accept to use, during sexual intercourse, 2 highly effective contraception methods
Males patient, whose partners are pregnant, must use, during sexual intercourse, a condom from the inclusion up to 4 months after investigational medicinal product administration.
Males patient who has agreed not to donate sperm for 4 months after product administration.

Exclusion criteria:

Significant medical diseases or conditions, including poorly controlled hypertension, cardiovascular disease, inflammatory disorders, immunodeficiency, autoimmune disease, renal failure, liver dysfunction, cancer (except treated basal skin cell carcinoma), or active infection.
Frequent headaches and/or migraine, recurrent nausea and/or vomiting.
History or presence of drug or alcohol abuse.
Smoking more than 5 cigarettes or equivalent per day.
If female, pregnancy, lactating, or breast-feeding.
Patients with relapsing-remitting MS.
Treatment with natalizumab, methotrexate, azathioprine, or cyclosporine in the past 6 months.
Treatment with mitoxantrone, cyclophosphamide, cladribine, rituximab or any other immunosuppressant or cytotoxic therapy (other than steroids) in the last 12 months, or determined by the treating physician to have residual immune suppression from these treatments.
Treatment with glatiramer acetate or interferon beta in the past 4 weeks.
Treatment with fingolimod within the past 2 months.
Treatment with dimethyl fumarate in past 4 weeks.
Treatment with teriflunomide within the past 12 months unless patient has completed an accelerated clearance with cholestyramine.
Previous treatment with alemtuzumab.
Live, attenuated vaccine within 3 months prior to the randomization visit, such as varicella-zoster, oral polio, and rubella vaccines.
Clinically significant abnormality in thyroid function.
Inability to undergo magnetic resonance imaging with gadolinium administration.
Hypersensitivity or contraindication to acyclovir.
Known bleeding disorder.
Significant autoimmune disease.
Active infection or at high risk for infection.
Latent or active tuberculosis.
Major psychiatric disorder that is not adequately controlled by treatment.
Epileptic seizures that are not adequately controlled by treatment.
Prior history of invasive fungal infections.

Indapta Multiple Sclerosis: A Phase 1B Study of IDP-023 G-NK Cells Plus Ocrelizumab in Patients with Progressive Multiple Sclerosis

Inclusion Criteria:

TBD

Exclusion Criteria:

TBD