Progressive Multiple SclerosisPhase 1NCT06451159
A Study of KYV-101, a CD19 CAR T Cell Therapy, in Participants With Treatment Refractory Progressive Multiple Sclerosis
A Phase 1 study testing KYV-101 (Biological) - 0.33 ×10^8 cells, KYV-101 (Biological) - 1 ×10^8 cells and Chemotherapy: cyclophosphamide (CYC) in people with Progressive Multiple Sclerosis, run by Bruce Cree at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 25 to 70 years
- Conditions the study is for
- Progressive Multiple Sclerosis
- What is being tested?
- KYV-101 (Biological) - 0.33 ×10^8 cells, KYV-101 (Biological) - 1 ×10^8 cells and Chemotherapy: cyclophosphamide (CYC)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jun 2024to Feb 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Documented evidence of clinical disability progression within the 2 years prior to inclusion, i.e. a) progression of EDSS during the past two years of at least 1 point sustained for at least 6 months if inclusion EDSS is from 3.5 to 5.5 or at least 0.5 point increase sustained for at least 6 months if inclusion EDSS is from 6 to 6.5 or b) increase of Timed Walk 25 (TW25) by at least 20% in the last two years sustained for at least 6 months or c) other well-documented objective worsening despite at least 1 year of prior treatment for progressive forms of MS (including siponimod, and/or anti- B-lymphocyte antigen (CD20) MAb).
Show all 19Show fewer
- 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.
- Male participants, if not surgically sterilized, must agree to use a highly effective method of contraception until 12 months post IP infusion.
- Women and men must agree not to donate eggs (ova, oocytes) or sperm, respectively, until at least 12 months after receiving a KYV-101 infusion.
- Ability to obtain adequate vascular access for leukapheresis procedure (either peripheral line or surgically placed line).
Who cannot join
- 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.
Show all 40Show fewer
- 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.
- Untreated active or untreated latent tuberculosis or documented completed treatment without a negative chest X-ray (CXR) that shows no evidence of active Tuberculosis (TB).
- Primary immunodeficiency as defined by a known genetic disorder.
- History of splenectomy.
- Impaired cardiac function or clinically significant cardiac disease including:
- Unstable angina or myocardial infarction or coronary artery bypass graft (CABG) within 6 months prior to apheresis.
- New York Heart Association (NYHA) stage III or IV congestive heart failure.
- History of clinically significant cardiac arrhythmia (eg, ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block, or QT prolongation.
- Inadequate cardiac function defined as left ventricular ejection fraction (LVEF) < 40% as assessed by echocardiogram within 3 months of screening. Repeat testing may occur at Investigator's discretion.
- 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.
- A primary malignancy which has been completely resected, or treated, and is in complete remission for at least 5 years prior to screening.
- Serious and/or uncontrolled medical condition 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.
- Chronic viral, bacterial, or systemic fungal infection that may be reactivated during treatment.
- Requirement of supplemental oxygen to maintain oxygen saturation.
- Clinical evidence of dementia.
- A thromboembolic event within 6 months prior to apheresis.
- On anti-coagulation agents that would be unsafe to transiently hold for medical procedures.
- Uncontrolled Diabetes Mellitus (DM) or Hypertension (HTN).
- Major surgery within 4 weeks prior to apheresis or planned within 4 weeks after KYV-101 administration. For surgery planned after 4 weeks post KYV-101 administration, discuss with the investigator.
- History of any other neurologic disorder or medical condition the investigator considers would increase the risk for the participant, including seizure disorders.
- Contraindications or life-threatening allergies, hypersensitivity, or intolerance to KYV-101 or its excipients, including dimethyl sulfoxide; cyclophosphamide (CYC) or fludarabine (FLU); or tocilizumab.
- Pregnant or breastfeeding; or plans to become pregnant or breastfeed within 24 months after receiving the KYV-101 infusion.
- Unwilling to participate in long-term follow up for safety monitoring after CAR-T therapy.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco, Multiple Sclerosis Center
San Francisco, California, 94158
About this study
Official title: 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 Participants With Treatment Refractory Progressive Multiple Sclerosis
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?
Read more
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.
Read the detailed description
This study will treat up to 10 participants. The primary objective is to characterize central nervous system (CNS) penetration of KYV-101 and its effectiveness of target engagement via elimination of oligoclonal bands (OCB) and/or normalization of immunoglobulin G (IgG) IgG index and to characterize a preliminary safety profile of KYV-101 in treatment-refractory MS.
Pharmacodynamics (PD)/Pharmacokinetics (PK) Objectives
- To characterize the PK and PD of KYV 101 in blood.
- To evaluate changes in PD and disease-related biomarkers.
- To assess the immunophenotype of Chimeric Antigen Receptor (CAR) T cells.
Pharmacodynamics/Pharmacokinetics Endpoints
- CAR-positive T cell counts, CAR transgene level, B-cell counts over time, systemic cytokine concentrations.
- Immunophenotype B and T cells through flow cytometry (including non-CAR T cell and B-cell subsets, if detectable), serum proteins and gene expression analysis.
- CAR T cell phenotypic composition as defined by markers of activation, proliferation, differentiation, and exhaustion (prior to and post infusion).
Abbreviations: CAR=chimeric antigen receptor; PD=pharmacodynamics; PK=pharmacokinetics
Safety/Adverse Event Objectives
- To evaluate for disease re-activation.
- To evaluate the immunogenicity (humoral response) of KYV-101.
- To evaluate the immunogenicity (cellular response) of KYV-101.
- To determine whether RCL is present in participants who receive KYV-101.
- To evaluate changes in long-term humoral response after KYV-101.
- To assess mood patient-reported outcomes (PROs) after infusion of KYV-101.
Safety/Adverse Event Endpoints
- Disease reactivation as defined by the presence of new T2 hyperintense or gadolinium (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 (RCL) 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 Columbia Suicide Severity Rating Scale (C-SSRS).
Abbreviations: RCL=replication competent lentivirus; VSV-G qPCR=vesicular stomatitis virus G glycoprotein quantitative polymerase chain reaction; PRO=patient reported outcomes; C-SSRS=Columbia Suicide severity rating scale
The safety and tolerability of KYV-101 will be evaluated by reported adverse events (AEs), physical examination findings, vital sign measurements, neurological assessment, and laboratory analyses.
- Conditions
- Progressive Multiple Sclerosis
- Being tested
- KYV-101 (Biological) - 0.33 ×10^8 cells, KYV-101 (Biological) - 1 ×10^8 cells, Chemotherapy: cyclophosphamide (CYC), Chemotherapy: fludarabine (FLU)
- Keywords
- multiple sclerosis, CAR-T, University of California, San Francisco (UCSF), progressive multiple sclerosis, treatment refractory progressive multiple sclerosis
- Medical subject headings
- Multiple Sclerosis, Chronic Progressive, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KYV-101 (Biological) - 0.33 ×10^8 cellsBiological
Also called CAR T-cell therapy
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.
KYV-101 (Biological) - 1 ×10^8 cellsBiological
Also called CAR T-cell therapy
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.
Chemotherapy: cyclophosphamide (CYC)Drug
Participants will receive one 3-day cycle of lymphodepletion with CYC 300 mg/m2 prior to administration of KYV-101.
Chemotherapy: fludarabine (FLU)Drug
Participants will receive one 3-day cycle of lymphodepletion with FLU 30 mg/m2 prior to administration of KYV-101.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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). Receives: Biological: KYV-101 (Biological) - 1 ×10^8 cells; Drug: Chemotherapy: cyclophosphamide (CYC); Drug: Chemotherapy: fludarabine (FLU) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The presence of CAR-T cells in CSF following their peak expansion in peripheral blood.
To surmise CNS penetration of CAR-T cells.
Measured: 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.
Measured: 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.
To characterize the evidence of target engagement within the CNS of KYV-101.
Measured: Screening to Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2024
- Study start20 Jun 2024
- Primary completion1 Feb 2026
- Study completionFeb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Progressive Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bruce Cree
- Sponsor type
- University, hospital or other
- Collaborators
- Kyverna Therapeutics
- Responsible party
- Sponsor-investigator, Bruce Cree, University of California, San Francisco
- Investigators
- Bruce Cree, MD, PhD, MAS, Principal investigator, University of California, San FranciscoSasha Gupta, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06451159
- Sponsor's protocol ID
- 23-40657
- Status last verified
- Jun 2026
- First submitted
- 3 Jun 2024
- Last updated
- 10 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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 Participants With Treatment Refractory Progressive Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT06451159
- Acronym / sponsor ID
- 23-40657
- Conditions
- Progressive Multiple Sclerosis
- Keywords
- multiple sclerosis, CAR-T, University of California, San Francisco (UCSF), progressive multiple sclerosis, treatment refractory progressive multiple sclerosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Bruce CreeUniversity, hospital or other
- Collaborators
- Kyverna Therapeutics
- Study start
- 20 Jun 2024 (actual)
- Primary completion
- 1 Feb 2026 (actual)
- Study completion
- Feb 2027 (estimated)
- First posted
- 11 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study will treat up to 10 participants. The primary objective is to characterize central nervous system (CNS) penetration of KYV-101 and its effectiveness of target engagement via elimination of oligoclonal bands (OCB) and/or normalization of immunoglobulin G (IgG) IgG index and to characterize a preliminary safety profile of KYV-101 in treatment-refractory MS.
Pharmacodynamics (PD)/Pharmacokinetics (PK) Objectives
- To characterize the PK and PD of KYV 101 in blood.
- To evaluate changes in PD and disease-related biomarkers.
- To assess the immunophenotype of Chimeric Antigen Receptor (CAR) T cells.
Pharmacodynamics/Pharmacokinetics Endpoints
- CAR-positive T cell counts, CAR transgene level, B-cell counts over time, systemic cytokine concentrations.
- Immunophenotype B and T cells through flow cytometry (including non-CAR T cell and B-cell subsets, if detectable), serum proteins and gene expression analysis.
- CAR T cell phenotypic composition as defined by markers of activation, proliferation, differentiation, and exhaustion (prior to and post infusion).
Abbreviations: CAR=chimeric antigen receptor; PD=pharmacodynamics; PK=pharmacokinetics
Safety/Adverse Event Objectives
- To evaluate for disease re-activation.
- To evaluate the immunogenicity (humoral response) of KYV-101.
- To evaluate the immunogenicity (cellular response) of KYV-101.
- To determine whether RCL is present in participants who receive KYV-101.
- To evaluate changes in long-term humoral response after KYV-101.
- To assess mood patient-reported outcomes (PROs) after infusion of KYV-101.
Safety/Adverse Event Endpoints
- Disease reactivation as defined by the presence of new T2 hyperintense or gadolinium (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 (RCL) 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 Columbia Suicide Severity Rating Scale (C-SSRS).
Abbreviations: RCL=replication competent lentivirus; VSV-G qPCR=vesicular stomatitis virus G glycoprotein quantitative polymerase chain reaction; PRO=patient reported outcomes; C-SSRS=Columbia Suicide severity rating scale
The safety and tolerability of KYV-101 will be evaluated by reported adverse events (AEs), physical examination findings, vital sign measurements, neurological assessment, and laboratory analyses.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dosing Cohort #1: KYV-101 CAR+ T -- 0.33 ×10^8 cells | Experimental | Biological: KYV-101 (Biological) - 0.33 ×10^8 cells, Drug: Chemotherapy: cyclophosphamide (CYC), Drug: Chemotherapy: fludarabine (FLU)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. |
| Dosing Cohort #2: KYV-101 CAR+ T -- 1×10^8 cells | Experimental | Biological: KYV-101 (Biological) - 1 ×10^8 cells, Drug: Chemotherapy: cyclophosphamide (CYC), Drug: Chemotherapy: fludarabine (FLU)An additional five participants are planned for enrollment at the higher dose level (1×10^8 cells). |
Who may qualify
- Ages
- 25 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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
Key exclusion criteria (40 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KYV-101 (Biological) - 0.33 ×10^8 cellsAlso: CAR T-cell therapyKYV-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. | Biological | Dosing Cohort #1: KYV-101 CAR+ T -- 0.33 ×10^8 cells |
| KYV-101 (Biological) - 1 ×10^8 cellsAlso: CAR T-cell therapyKYV-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. | Biological | Dosing Cohort #2: KYV-101 CAR+ T -- 1×10^8 cells |
| Chemotherapy: cyclophosphamide (CYC)Participants will receive one 3-day cycle of lymphodepletion with CYC 300 mg/m2 prior to administration of KYV-101. | Drug | 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)Participants will receive one 3-day cycle of lymphodepletion with FLU 30 mg/m2 prior to administration of KYV-101. | Drug | Dosing Cohort #1: KYV-101 CAR+ T -- 0.33 ×10^8 cells, Dosing Cohort #2: KYV-101 CAR+ T -- 1×10^8 cells |
Primary outcome
The presence of CAR-T cells in CSF following their peak expansion in peripheral blood.
Time frame: Screening to Week 48
To surmise CNS penetration of CAR-T cells.
The incidence and severity of adverse events and dose-limiting toxicities.
Time frame: Screening to Week 48
* 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.
1 secondary outcome
The proportion of participants in whom reduction of CSF OCB and/or normalization of CSF IgG Index are detected.
Time frame: Screening to Week 48
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2026.
- Individual participant dataSharing planned: No
Related trials for Progressive Multiple Sclerosis
RecruitingPhase 3
A Study of Orelabrutinib in Patients With Secondary Progressive Multiple Sclerosis
Secondary Progressive Multiple Sclerosis
RecruitingPhase 3
A Study of Orelabrutinib in Patients With Primary Progressive Multiple Sclerosis
Multiple Sclerosis (MS) Primary Progressive
RecruitingPhase 2
A Phase 2a Study of SUN-627 in Participants With Non-Active Secondary Progressive and Primary Progressive Multiple Sclerosis (SPMS/PPMS)
Primary Progressive Multiple Sclerosis, Primary Progressive MS
RecruitingPhase 4
A Study of Ocrelizumab Administered Subcutaneously in Participants With Multiple Sclerosis Who Switch From an Approved Anti-CD20 Therapy
Multiple Sclerosis
RecruitingObservational study
Natural History Study of Progressive Multifocal Leukoencephalopathy (PML)
Progressive Multifocal Leukoencephalopathy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruce Cree, MD, PhD, MAS principal investigator
University of California, San Francisco
Sasha Gupta, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing KYV-101 (Biological) - 0.33 ×10^8 cells, KYV-101 (Biological) - 1 ×10^8 cells and Chemotherapy: cyclophosphamide (CYC) in people with Progressive Multiple Sclerosis, run by Bruce Cree at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 10 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The presence of CAR-T cells in CSF following their peak expansion in peripheral blood. (time frame: Screening to Week 48). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2026.