KYSA-6: A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy, in Patients With Generalized Myasthenia Gravis

Kyverna Therapeutics

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Myasthenia Gravis; Generalized Myasthenia Gravis

Treatments: Biological: KYV-101; Drug: Standard lymphodepletion regimen; Drug: Standard of Care Treatment

Study type: Interventional

Funder types: Industry

Identifiers

NCT06193889

KYSA-6

KYV101-006

Details and patient eligibility

About

A Study of the Anti-CD 19 Chimeric Antigen Receptor T Cell Therapy for Patients with Myasthenia Gravis

Full 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).

Enrollment: 66 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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66 participants in 3 patient groups

KYV-101 CAR-T cells with lymphodepletion conditioning

Experimental group

Description:

Phase 2: Dosing with KYV-101 CAR-T cells

Treatment:

Drug: Standard lymphodepletion regimen

Biological: KYV-101

KYV-101 Treatment

Experimental group

Description:

Phase 3

Treatment:

Drug: Standard lymphodepletion regimen

Biological: KYV-101

Standard of Care

Active Comparator group

Description:

Phase 3 Optional crossover to receive KYV-101 Treatment after 24 weeks

Treatment:

Drug: Standard of Care Treatment

Drug: Standard lymphodepletion regimen

Biological: KYV-101