A Study of KYV-101, a CD19 CAR T Cell Therapy, in Participants With Treatment Refractory Progressive Multiple Sclerosis

NCT06451159 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 23-40657
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to test a drug called KYV-101 in people who have progressive multiple sclerosis (MS) and who have not responded to standard therapies to slow disease progression. The main questions it aims to answer are:

• What is the highest therapy dose that can be given without causing harm?
• Can this therapy enter the central nervous system? Participants will be asked to:
• Attend 14 visits plus an 8-day inpatient hospital stay over the course of 58 weeks.
• Complete apheresis and chemotherapy treatments in preparation for KVY-101 therapy.
• Undergo medical and research testing such as physical and neurological exams, MRI, lumbar puncture, blood draws, questionnaires, and vision assessments.

Conditions

Progressive Multiple Sclerosis

Keywords

multiple sclerosis; CAR-T; University of California, San Francisco (UCSF); progressive multiple sclerosis; treatment refractory progressive multiple sclerosis

Outcome Measures

Primary Outcomes (2)

• The presence of CAR-T cells in CSF following their peak expansion in peripheral blood.

  To surmise CNS penetration of CAR-T cells.

  Screening to Week 48

• The incidence and severity of adverse events and dose-limiting toxicities.

  * Disease reactivation as defined by the presence of new T2 hyperintense or GAD enhancing lesions on MRI brain at 8 weeks post-infusion of KYV-101. * Incidence of detectable anti-KYV-101 antibodies in peripheral blood. * Incidence of detectable T cells specific to KYV-101 drug product in peripheral blood. * Detectable replication competent lentivirus as measured by surrogate assay (VSV-G qPCR). * Persistence of IgG antibody titers to common vaccine related antigens (varicella, measles, mumps, rubella, tetanus). * Change from baseline in depression/anxiety including C-SSRS.

  Screening to Week 48

Secondary Outcomes (1)

• The proportion of participants in whom reduction of CSF OCB and/or normalization of CSF IgG Index are detected.

  Screening to Week 48

Study Arms (2)

Dosing Cohort #1: KYV-101 CAR+ T -- 0.33 ×10^8 cells

EXPERIMENTAL

Five participants will be enrolled at the lower dose (0.33 ×10\^8 cells). Once safety and tolerability are adequately assessed, treatment will proceed to the higher dose level.

Biological: KYV-101 (Biological) - 0.33 ×10^8 cells; Drug: Chemotherapy: cyclophosphamide (CYC); Drug: Chemotherapy: fludarabine (FLU)

Dosing Cohort #2: KYV-101 CAR+ T -- 1×10^8 cells

EXPERIMENTAL

An additional five participants are planned for enrollment at the higher dose level (1×10\^8 cells).

Biological: KYV-101 (Biological) - 1 ×10^8 cells; Drug: Chemotherapy: cyclophosphamide (CYC); Drug: Chemotherapy: fludarabine (FLU)

Interventions

KYV-101 (Biological) - 0.33 ×10^8 cells BIOLOGICAL

KYV-101 is a type of treatment called CAR T-cell therapy. It uses cells from your own immune system, called T-cells, to attack cells that cause inflammation. T-cells are a type of white blood cell.

Also known as: CAR T-cell therapy

Dosing Cohort #1: KYV-101 CAR+ T -- 0.33 ×10^8 cells

KYV-101 (Biological) - 1 ×10^8 cells BIOLOGICAL

KYV-101 is a type of treatment called CAR T-cell therapy. It uses cells from your own immune system, called T-cells, to attack cells that cause inflammation. T-cells are a type of white blood cell.

Also known as: CAR T-cell therapy

Dosing Cohort #2: KYV-101 CAR+ T -- 1×10^8 cells

Chemotherapy: cyclophosphamide (CYC) DRUG

Participants will receive one 3-day cycle of lymphodepletion with CYC 300 mg/m2 prior to administration of KYV-101.

Dosing Cohort #1: KYV-101 CAR+ T -- 0.33 ×10^8 cells; Dosing Cohort #2: KYV-101 CAR+ T -- 1×10^8 cells

Chemotherapy: fludarabine (FLU) DRUG

Participants will receive one 3-day cycle of lymphodepletion with FLU 30 mg/m2 prior to administration of KYV-101.

Dosing Cohort #1: KYV-101 CAR+ T -- 0.33 ×10^8 cells; Dosing Cohort #2: KYV-101 CAR+ T -- 1×10^8 cells

Eligibility Criteria

• Age: 25 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must sign a written informed consent form (ICF) prior to any screening procedures.
• Participant must be 25-70 years of age (inclusive).
• Clinical diagnosis of MS with evidence of primary or secondary progressive MS based on 2017 International Panel Criteria (Thompson 2018).
• Historical documented presence of CSF restricted OCBs or elevated IgG Index (reconfirmed on screening).
• Expanded disability status score (EDSS) score 3.0-7.0
• Adequate organ function as per below:
• Hematology- Hemoglobin \> 8 g/dl (without prior red blood cell transfusion within 7 days before the laboratory test) Platelets \> 50,000/µL (without transfusion support within 7 days before the laboratory test) Absolute Neutrophil Count (ANC) \>1,000/µL (prior growth factor support is permitted but must be without support in the 7 days prior to the laboratory test) Absolute Lymphocyte Count (ALC) \> 500/µL IgG \> 600 mg/dL Hepatic- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 ×upper limit of normal (ULN) Total bilirubin ≤ 1.5 mg/dl, except with Gilbert's syndrome Renal- estimated Glomerular Filtration Rate (eGFR) \> 45 mL/min/1.73 m2 (measured by Chronic Kidney Disease (CKD) - Epidemiology Collaboration (EPI) 2021 equation)
• Positive varicella zoster virus titer. Participants who test seronegative for varicella zoster virus IgG antibodies will be recommended to obtain vaccination prior to Investigational Product (IP) infusion.
• Participants are recommended to be up to date on other recommended vaccinations, including against Coronavirus Disease (COVID-19)/ Severe Acute Respiratory Syndrome (SARS) Coronavirus 2 (CoV-2), per Centers for Disease Control and Prevention or institutional guidelines for immune-compromised individuals.
• Women of childbearing potential must have a negative pregnancy test at screening, prior to apheresis, and prior to lymphodepletion chemotherapy using a highly sensitive serum pregnancy test (β- human Chorionic Gonadotropin (hCG)). A woman of childbearing potential is defined as a sexually mature woman who has not undergone a hysterectomy or tubal ligation or who has not been naturally postmenopausal for at least 24 consecutive months.
• Female participants of childbearing potential who have a fertile male sexual partner must agree to use a highly effective method of contraception (failure rate of \< 1% per year when used consistently and correctly) from the time of signing the ICF until 24 months after the KYV-101 infusion. Examples of highly effective method of contraception include:
• Established use of hormonal methods of contraception associated with inhibition of ovulation (e.g. oral, inserted, injected, implanted, transdermal), provided the participant or male participant's female partner plans to remain on the same treatment throughout the entire study and has been using that hormonal contraceptive for adequate time to ensure effectiveness.
• Correctly placed copper containing- intrauterine device or intrauterine hormone-replacing system.
• Female sterilization (bilateral tubal ligation/bilateral salpingectomy or bilateral tubal occlusive procedure (with confirmed occlusion).
• Sexual abstinence, defined as completely and persistently refraining from all heterosexual intercourse (including during the entire period of risk associated with the study treatments) may obviate the need for contraception only if this is the preferred and usual lifestyle of the participant.

You may not qualify if:

• MS clinical stability on Disease Modifying Therapy (DMT) therapy.
• Clinical relapse in the two years prior to study entry.
• Disease other than MS to explain the first demyelinating event; including Aquaporin-4 (AQP4) IgG or Myelin oligodendrocyte glycoprotein (MOG)-IgG seropositivity.
• Unwilling or unsafe to proceed with cerebral spinal fluid (CSF) exams based on coagulopathy or anatomy or other considerations in the judgment of the study investigator.
• Unwilling or unsafe to proceed with MRI.
• History of allogeneic or autologous stem cell transplant or solid organ transplant.
• Prior treatment CAR-T or gene therapy product directed at any target.
• Prior treatment with mitoxantrone, cladribine or alemtuzumab.
• Need for ongoing anticoagulation.
• Presence of hypogammaglobulinemia defined as IgG \< 600 mg/dL.
• Plan to receive live, attenuated vaccine after signing ICF (inactive vaccines, like the influenza vaccine, are allowed).
• Unable to interrupt autoimmune disease therapy prior to apheresis
• Serologic status reflecting active hepatitis B or C infection. Patients who are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.) Patients who are positive for hepatitis B core antibody will be required to remain on appropriate prophylactic antiviral therapy (e.g. with entecavir) for the duration of the study.
• Positive serology for human immunodeficiency virus (HIV).
• History of progressive multifocal leukoencephalopathy.

Sponsors & Collaborators

• Bruce Cree: lead
• Kyverna Therapeutics: collaborator

Study Sites (1)

University of California, San Francisco, Multiple Sclerosis Center

San Francisco, California, 94158, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis

Interventions

Biological Products; Immunotherapy, Adoptive

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Complex Mixtures; Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Bruce Cree, MD, PhD, MAS

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Sasha Gupta, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD, MAS, Professor

Study Record Dates

• First Submitted: June 3, 2024
• First Posted: June 11, 2024
• Study Start: June 20, 2024
• Primary Completion: February 1, 2026
• Study Completion (Estimated): February 1, 2027
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)