Myasthenia Gravis, Generalized Myasthenia Gravis
Conditions
Keywords
KYV-101, myasthenia gravis, autoimmune disease, anti-CD19 CAR-T Therapy, cellular therapy, MG, KYSA-6, KYV101-006
Brief summary
A Study of the Anti-CD 19 Chimeric Antigen Receptor T Cell Therapy for Patients with Myasthenia Gravis
Detailed description
Myasthenia gravis (MG) is a chronic autoimmune disease that affects the neuromuscular junction and is characterized by muscle weakness. B cells play a role in MG, and the disease is characterized by the presence of autoantibodies such as anti-AChR and anti-MuSK antibodies. CD-19 target chimeric antigen receptor (CAR) T cells harness the ability of cytotoxic T cells to directly and specifically lyse target cells to effectively deplete both normal and autoreactive B cells in the circulation as well as impacted lymphoid and potentially non-lymphoid tissues. KYV-101, a fully human anti-CD19 CAR T-cell therapy, will be investigated in adult subjects with myasthenia gravis (MG).
Interventions
DRUGStandard of Care Treatment
Standard of Care Medications Optional Crossover to receive KYV-101 treatment
Standard lymphodepletion regimen
BIOLOGICALKYV-101
Anti-CD19 CAR-T cell therapy
Sponsors
Kyverna Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria 1. Presence of autoantibodies to AChR or MuSK at screening. 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 pre-dose baseline 4. QMG total score of ≥11 at screening an confirmed at pre-dose baseline 5. Failed treatment with 2 or more immunosuppressive/immunomodulatory therapies, or failed at least 1 immunosuppressive therapy and required chronic plasmapheresis, or IVIG (\>4 times/year over ≥12 months) 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. No use of FcRn inhibitors within 4 weeks prior to screening Key
Exclusion criteria
1. Unable to washout or interrupt autoimmune disease therapy prior to apheresis 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and severity of adverse events (AEs) and laboratory abnormalities (Phase 2) | 2 years |
| Efficacy of KYV-101 via Myasthenia Gravis Activities of Daily Living (MG-ADL) change from baseline (Phase 2) | 24 weeks |
| Efficacy of KYV-101 via Myasthenia Gravis Activities of Daily Living (MG-ADL) change from baseline for KYV-101 Treatment Arm to Standard of Care Arm (Phase 3) | 24 weeks |
| Efficacy of KYV-101 via Quantitative Myasthenia Gravis (QMG) change from baseline for KYV-101 Treatment arm to Standard of Care arm | 24 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy of KYV-101 via Myasthenia Gravis Composite (MGC) score change from baseline for KYV-101 arm to Standard of Care arm (Phase 3) | 24 weeks |
| Efficacy of KYV-101 via Percent change from baseline in anti acetylcholine receptors (anti-AChR) antibody levels for KYV-101 Treatment arm to Standard of Care arm (Phase 3) | 24 weeks |
| Efficacy of KYV-101 via Percent change from baseline in anti muscle-specific tyrosine kinase (anti-MuSK) antibody levels for KYV-101 Treatment arm to Standard of Care arm (Phase 3) | 24 weeks |
| Efficacy of KYV-101 via Proportion of patients with a ≥3 point improvement from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) for KYV-101 Treatment arm to Standard of Care arm (Phase 3) | 24 weeks |
| Efficacy of KYV-101 via Proportion of patients with minimal symptom expression (MSE) for KYV-101 Treatment arm to Standard of Care arm (Phase 3) | 24 weeks |
| Efficacy of KYV-101 via Myasthenia Gravis Quality of Life 15-item Scale (MG-QoL 15r) change from baseline for KYV-101 Treatment arm to Standard of Care arm (Phase 3) | 24 weeks |
| Incidence and severity of adverse events (AEs) and laboratory abnormalities (Phase 3) | 2 years |
Countries
Brazil, Germany, United States
Contacts
CONTACTKyverna Therapeutics, Inc.
STUDY_DIRECTORMD
Kyverna Therapeutics, Inc.
Outcome results
None listed