Multiple Sclerosis, Primary ProgressivePhase 2NCT06384976
KYSA-7: A Study of Anti-CD19 CAR T-Cell Therapy, in Subjects With Refractory Primary and Secondary Progressive Multiple Sclerosis
A Phase 2 study testing KYV-101, Standard lymphodepletion regimen and Anti-CD20 mAB in people with Multiple Sclerosis, Primary Progressive and Multiple Sclerosis, Secondary Progressive, run by Kyverna Therapeutics at 1 site in United States.
Trial summary
A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects with Refractory Primary and Secondary Progressive Multiple Sclerosis Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Multiple Sclerosis, Primary Progressive, Multiple Sclerosis, Secondary Progressive, Multiple Sclerosis
- What is being tested?
- KYV-101, Standard lymphodepletion regimen and Anti-CD20 mAB
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Sep 2024to Jan 2029
- Phase
- Phase 2
- 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 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Subject must have a history of diagnosis of primary progressive or secondary progressive MS.
- History of treatment with anti-CD20 mAb with continuing evidence of worsening physical disability over a period of ≥6 months, with documented clinical disability progression within the 2 years prior to inclusion.
Who cannot join
- Monophasic disease, radiologically isolated syndrome, clinically isolated syndrome, progressive solitary sclerosis or relapsing-remitting disease as defined by the 2017 McDonald criteria.
- History of CNS or spinal cord tumor, metabolic or infectious cause of myelopathy, genetically inherited progressive CNS disorder, sarcoidosis, non-MS progressive neurologic condition or PML.
- Prior treatment with cellular therapy (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
Show all 14Show fewer
- 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
- A primary malignancy which has been completely resected, or treated, and is in complete remission for at least 5 years prior to screening
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University Medical Center
Palo Alto, California, 94305
About this study
Official title: KYSA-7: 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
A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects with Refractory Primary and Secondary Progressive Multiple Sclerosis
Read the detailed description
Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease in which lymphocytes at first attack the myelin sheaths within the central nervous system (CNS), accompanied or later followed by axonal damage. B cells play a central and multifunctional role in the immunopathogenesis of MS. B cells present antigen to T cells in stimulating a pro-inflammatory immune cascade, secrete pathogenic cytokines, moderate T cell and myeloid cell functions, form structural B cell meningeal follicles within the human central nervous system and produce pathogenic antibodies upon evolution to plasma cells.
CD19-targeted chimeric antigen receptor (CAR) T cells harness the ability of cytotoxic T cells to directly and specifically lyse target cells to effectively deplete B cells in the circulation and in lymphoid and potentially non-lymphoid tissues. KYV-101, a fully human anti-CD19 CAR T-cell therapy, will be investigated in adult subjects with refractory primary and secondary progressive multiple sclerosis.
- Conditions
- Multiple Sclerosis, Primary Progressive, Multiple Sclerosis, Secondary Progressive, Multiple Sclerosis, MS
- Being tested
- KYV-101, Standard lymphodepletion regimen, Anti-CD20 mAB
- Keywords
- KYV-101, multiple sclerosis, autoimmune disease, anti-CD19 CAR-T therapy, cellular therapy, MS
- Medical subject headings
- Multiple Sclerosis, Chronic Progressive, Multiple Sclerosis, Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KYV-101Biological
Anti-CD19 CAR-T cell therapy
Standard lymphodepletion regimenDrug
CYC/FLU
Anti-CD20 mABDrug
Anti-CD20 mAB
| Study group | Role | What they receive |
|---|---|---|
| KYV-101 CAR-T cells with lymphodepletion conditioning | Experimental | Dosing with KYV-101 CAR T cells Receives: Biological: KYV-101; Drug: Standard lymphodepletion regimen |
| Anti- CD20 mAb | Active comparator | Dosing with anti-CD20 mAb Receives: Drug: Anti-CD20 mAB |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate efficacy of KYV-101
Confirmed disability Progression on the EDSS scale. The EDSS scale ranges from 0 to 10 in 0.5- unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist.
Measured: at least 12 weeks
Secondary outcomes (9)
To characterize the safety and tolerability of KYV-101
Incidence and severity of adverse events (AEs)
Measured: Up to 2 years
To characterize the safety and tolerability of KYV-101
Incidence and severity of adverse events of special interests (AESIs)
Measured: Up to 2 years
To characterize the safety and tolerability of KYV-101
Incidence and severity of serious adverse events (SAEs)
Measured: Up to 2 years
To evaluate efficacy of KYV-101
Composite Confirmed Disability Progression (CCPD)
Measured: up to 12 weeks
To characterize the pharmacokinetics (PK)
Levels of Chimeric antigen receptor positive (CAR-positive) T cell counts
Measured: Up to 2 years
To characterize the pharmacokinetics (PK)
Levels of CAR Transgene levels
Measured: Up to 2 years
To characterize the Pharmacodynamics (PD)
Levels of B cell in the blood
Measured: Up to 2 years
To characterize the Pharmacodynamics (PD)
Serum cytokines will be measured by multiplexed mesoscale discovery (MSD) assay and will include cytokines historically associated with potential CAR T toxicity (CRS and ICANS) such as gamma interferon (IFNg) and interleukin 6 (IL-6).
Measured: Up to 2 years
To evaluate the immunogenicity (humoral response) of KYV-101
Percentage of participants who develop anti-KYV-101 antibodies by immunoassays)
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2024
- Study start20 Sep 2024
- Primary completionApr 2027 (estimated)
- Study completionJan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple Sclerosis, Primary ProgressiveStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kyverna Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Kyverna Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06384976
- Sponsor's protocol ID
- KYSA-7
- Other IDs
- KYV101-007
- Status last verified
- Jan 2025
- First submitted
- 21 Nov 2023
- Last updated
- 13 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Silva BA, Miglietta E, Ferrari CC. Insights into the role of B cells in the cortical pathology of Multiple sclerosis: evidence from animal models and patients. Mult Scler Relat Disord. 2021 May;50:102845. doi: 10.1016/j.msard.2021.102845. Epub 2021 Feb 16.
PubMed 33636613
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- KYSA-7: 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
- ClinicalTrials.gov ID
- NCT06384976
- Acronym / sponsor ID
- KYSA-7
- Conditions
- Multiple Sclerosis, Primary Progressive, Multiple Sclerosis, Secondary Progressive, Multiple Sclerosis, MS
- Keywords
- KYV-101, multiple sclerosis, autoimmune disease, anti-CD19 CAR-T therapy, cellular therapy, MS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Kyverna TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 20 Sep 2024 (actual)
- Primary completion
- Apr 2027 (estimated)
- Study completion
- Jan 2029 (estimated)
- First posted
- 25 Apr 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.
A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects with Refractory Primary and Secondary Progressive Multiple Sclerosis
Detailed description
Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease in which lymphocytes at first attack the myelin sheaths within the central nervous system (CNS), accompanied or later followed by axonal damage. B cells play a central and multifunctional role in the immunopathogenesis of MS. B cells present antigen to T cells in stimulating a pro-inflammatory immune cascade, secrete pathogenic cytokines, moderate T cell and myeloid cell functions, form structural B cell meningeal follicles within the human central nervous system and produce pathogenic antibodies upon evolution to plasma cells.
CD19-targeted chimeric antigen receptor (CAR) T cells harness the ability of cytotoxic T cells to directly and specifically lyse target cells to effectively deplete B cells in the circulation and in lymphoid and potentially non-lymphoid tissues. KYV-101, a fully human anti-CD19 CAR T-cell therapy, will be investigated in adult subjects with refractory primary and secondary progressive multiple sclerosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| KYV-101 CAR-T cells with lymphodepletion conditioning | Experimental | Biological: KYV-101, Drug: Standard lymphodepletion regimenDosing with KYV-101 CAR T cells |
| Anti- CD20 mAb | Active comparator | Drug: Anti-CD20 mABDosing with anti-CD20 mAb |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Subject must have a history of diagnosis of primary progressive or secondary progressive MS.
- History of treatment with anti-CD20 mAb with continuing evidence of worsening physical disability over a period of ≥6 months, with documented clinical disability progression within the 2 years prior to inclusion.
Key exclusion criteria (14 listed)
- Monophasic disease, radiologically isolated syndrome, clinically isolated syndrome, progressive solitary sclerosis or relapsing-remitting disease as defined by the 2017 McDonald criteria.
- History of CNS or spinal cord tumor, metabolic or infectious cause of myelopathy, genetically inherited progressive CNS disorder, sarcoidosis, non-MS progressive neurologic condition or PML.
- Prior treatment with cellular therapy (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
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-101Anti-CD19 CAR-T cell therapy | Biological | KYV-101 CAR-T cells with lymphodepletion conditioning |
| Standard lymphodepletion regimenCYC/FLU | Drug | KYV-101 CAR-T cells with lymphodepletion conditioning |
| Anti-CD20 mABAnti-CD20 mAB | Drug | Anti- CD20 mAb |
Primary outcome
To evaluate efficacy of KYV-101
Time frame: at least 12 weeks
Confirmed disability Progression on the EDSS scale. The EDSS scale ranges from 0 to 10 in 0.5- unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist.
9 secondary outcomes
To characterize the safety and tolerability of KYV-101
Time frame: Up to 2 years
To characterize the safety and tolerability of KYV-101
Time frame: Up to 2 years
To characterize the safety and tolerability of KYV-101
Time frame: Up to 2 years
To evaluate efficacy of KYV-101
Time frame: up to 12 weeks
To characterize the pharmacokinetics (PK)
Time frame: Up to 2 years
To characterize the pharmacokinetics (PK)
Time frame: Up to 2 years
To characterize the Pharmacodynamics (PD)
Time frame: Up to 2 years
To characterize the Pharmacodynamics (PD)
Time frame: Up to 2 years
To evaluate the immunogenicity (humoral response) of KYV-101
Time frame: Up to 2 years
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 13 Jan 2025.
- Background: PubMed 33636613Silva BA, Miglietta E, Ferrari CC. Insights into the role of B cells in the cortical pathology of Multiple sclerosis: evidence from animal models and patients. Mult Scler Relat Disord. 2021 May;50:102845. doi: 10.1016/j.msard.2021.102845. Epub 2021 Feb 16.
- Individual participant dataSharing planned: No
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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.
MD study director
Kyverna Therapeutics, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing KYV-101, Standard lymphodepletion regimen and Anti-CD20 mAB in people with Multiple Sclerosis, Primary Progressive and Multiple Sclerosis, Secondary Progressive, run by Kyverna Therapeutics 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 2 inclusion and 14 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 13 Jan 2025. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
To evaluate efficacy of KYV-101 (time frame: at least 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06384976, which also lists 1 linked publication.
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 13 Jan 2025.