Anti-CD19 CAR T-Cell Therapy for Refractory Myasthenia Gravis
KYSA-6: A Phase 2/3, Open-Label, Randomized, Controlled, Multicenter Study of KYV-101, an Autologous Fully Human Anti-CD19 Chimeric Antigen Receptor T-cell (CD19 CAR T) Therapy, Versus Ongoing Standard-Of-Care Immunosuppressive Therapy in Patients With Generalized Myasthenia Gravis
This study is testing a new CAR T-cell therapy to see if it can help adults with tough-to-treat myasthenia gravis feel better.
Quick facts
| Phase | Phase2; Phase3 |
|---|---|
| Study type | Interventional |
| Enrollment | 66 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | Kyverna Therapeutics Industry-sponsored |
| Drugs / interventions | rituximab, CAR T, immunotherapy, Chimeric Antigen Receptor |
| Locations | 16 sites (Orange, California and 15 other locations) |
| Trial ID | NCT06193889 on ClinicalTrials.gov |
What this trial studies
This study investigates the use of KYV-101, an anti-CD19 chimeric antigen receptor T-cell therapy, in adults with refractory generalized myasthenia gravis (MG). The approach targets and depletes both normal and autoreactive B cells, which are implicated in the autoimmune response associated with MG. Participants must have a confirmed diagnosis of MG with specific autoantibodies and have failed multiple prior treatments. The study aims to assess the efficacy and safety of this novel cellular therapy in improving symptoms of MG.
Who should consider this trial
Good fit: Ideal candidates are adults diagnosed with generalized myasthenia gravis who have specific autoantibodies and have not responded to previous treatments.
Not a fit: Patients who have not been diagnosed with myasthenia gravis or those who have not failed prior immunosuppressive therapies may not benefit from this study.
Why it matters
Potential benefit: If successful, this therapy could significantly improve muscle strength and quality of life for patients suffering from refractory myasthenia gravis.
How similar studies have performed: Other studies utilizing CAR T-cell therapies for autoimmune conditions have shown promising results, indicating potential for success in this novel application.
Eligibility criteria
Show full inclusion / exclusion criteria
Key Inclusion Criteria 1. Presence of autoantibodies to AChR or MuSK 2. Myasthenia Gravis Foundation of America (MGFA) Class II-IV 3. MG-Activities of Daily Living (MG-ADL) total score of ≥6 at screening and confirmed at baseline visit 4. QMG total score of ≥11 at screening an confirmed at baseline visit 5. Failed treatment with 2 or more immunosuppressive/immunomodulatory therapies, or failed at least 1 immunosuppressive therapy and required chronic plasmapheresis, or IVIG (or subcutaneous or intramuscular Ig) to control symptoms 6. On a stable dose of glucocorticoids and/or other immunotherapies for ≥1 month prior to screening. For patients treated with azathioprine, a stable dose for ≥2 months prior to screening is required 7. No change in dose of acetylcholinesterase inhibitors for ≥2 weeks prior to screening 8. No use of intravenous immune globulin (IVIG) or plasmapheresis (PLEX) within 4 weeks of screening or pre-dose baseline (unless this is part of their SOC treatment regimen) 9. No use of rituximab (or any other anti-CD20 or CD19 monoclonal antibody) within 12 weeks prior to screening 10. Able and willing to attend the necessary visits to the study site Key Exclusion Criteria 1. Unable to washout or interrupt autoimmune disease therapy prior to apheresis and/or baseline if required 2. Co-occurring neurological autoimmune disease (ie, Lambert-Eaton Myasthenic Syndrome) or any disease affecting the neuromuscular junction or muscle causing weakness (eg, myositis, myopathy, motor neuropathy) 3. History of stroke (with residual sequalae and/or risk for recurrence), seizure (even if well controlled on antiepileptics), neurodegenerative disease, altered mental status (unexplained and/or recent/current), or uncontrolled/severe psychiatric disease 4. Any 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, including but not limited to, clinically significant cardiac or pulmonary disease 5. History of primary immunodeficiency, organ or allogeneic bone marrow transplant, or splenectomy 6. Active, uncontrolled, viral, bacterial, or systemic fungal infection or recent history of repeated infections 7. Thymectomy \<12 months of screening or planned during the study 8. Prior treatment with gene therapy product or cellular immunotherapy (eg, CAR T) requiring vector integration and directed at any target 9. Patients requiring chronic anticoagulation therapy that cannot be discontinued for medical procedures
Where this trial is running
Orange, California and 15 other locations
- University of California, Irvine — Orange, California, United States (Recruiting)
- Stanford University Medical Center — Palo Alto, California, United States (Recruiting)
- University of Miami — Miami, Florida, United States (Recruiting)
- Indiana University Health — Indianapolis, Indiana, United States (Recruiting)
- University of Missouri — Columbia, Missouri, United States (Recruiting)
- Thomas Jefferson University Hospital — Philadelphia, Pennsylvania, United States (Recruiting)
- Houston Methodist Hospital — Houston, Texas, United States (Recruiting)
- Intermountain Medical Center — Murray, Utah, United States (Recruiting)
- Westmead Institute for Medical Research — Westmead, Australia (Recruiting)
- Hospital Israelita Albert Einstein — São Paulo, Brazil (Recruiting)
- Charite- Universitätsklinikum Berlin — Berlin, Germany (Recruiting)
- Universitätsklinikum der Ruhr-Universität Bochum — Bochum, Germany (Recruiting)
- Universitätsklinikum Hamburg-Eppendorf — Hamburg, Germany (Recruiting)
- Medizinische Hochscule Hannover — Hanover, Germany (Recruiting)
- Friedrich-Schiller-Universität Jena — Jena, Germany (Recruiting)
- Universitätsklinik Magdeburg — Magdeburg, Germany (Recruiting)
Study contacts
- Study coordinator: Kyverna Therapeutics, Inc.
- Email: Clinicaltrials@kyvernatx.com
- Phone: 510-925-2484
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.