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

Official title

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

Overview

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 (mivocabtagene autoleucel \[miv-cel\])), a fully human anti-CD19 CAR T-cell therapy, will be investigated in adult subjects with myasthenia gravis (MG).

Interventions

• Drug Standard of Care Treatment
  Standard of Care Medications Optional Crossover to receive KYV-101 treatment
• Drug Standard lymphodepletion regimen
  Standard lymphodepletion regimen
• Biological KYV-101
  Anti-CD19 CAR-T cell therapy

Primary outcome measures

• Incidence and severity of adverse events (AEs) and laboratory abnormalities (Phase 2) [Time frame: 18 months]
• Efficacy of KYV-101 via Myasthenia Gravis Activities of Daily Living (MG-ADL) change from baseline (Phase 2) [Time frame: 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) [Time frame: 24 weeks]
• Efficacy of KYV-101 via Quantitative Myasthenia Gravis (QMG) change from baseline for KYV-101 Treatment arm to Standard of Care arm (Phase 3) [Time frame: 24 weeks]

Secondary outcome measures (7)

• Efficacy of KYV-101 via Myasthenia Gravis Composite (MGC) score change from baseline for KYV-101 Treatment arm to Standard of Care arm (Phase 3) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 24 weeks]
• Incidence and severity of adverse events (AEs) and laboratory abnormalities (Phase 3) [Time frame: 18 months]

Eligibility criteria

Inclusion criteria

• Presence of autoantibodies to AChR or MuSK
• Myasthenia Gravis Foundation of America (MGFA) Class II-IV
• MG-Activities of Daily Living (MG-ADL) total score of ≥6 at screening and confirmed at baseline visit
• QMG total score of ≥11 at screening an confirmed at baseline visit
• 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
• 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
• No change in dose of acetylcholinesterase inhibitors for ≥2 weeks prior to screening
• 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)
• No use of rituximab (or any other anti-CD20 or CD19 monoclonal antibody) within 12 weeks prior to screening
• Able and willing to attend the necessary visits to the study site

Exclusion criteria

• Unable to washout or interrupt autoimmune disease therapy prior to apheresis and/or baseline if required
• 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)
• 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
• 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
• History of primary immunodeficiency, organ or allogeneic bone marrow transplant, or splenectomy
• Active, uncontrolled, viral, bacterial, or systemic fungal infection or recent history of repeated infections
• Thymectomy <12 months of screening or planned during the study
• Prior treatment with gene therapy product or cellular immunotherapy (eg, CAR T) requiring vector integration and directed at any target
• Patients requiring chronic anticoagulation therapy that cannot be discontinued for medical procedures

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 10 centers

• Ronald Reagan UCLA Medical Center — Los Angeles
• University of California, Irvine — Orange
• Stanford University Medical Center — Palo Alto
• University of Miami — Miami
• Indiana University Health — Indianapolis
• University of Missouri — Columbia
• Oregon Health & Science University — Portland
• Thomas Jefferson University Hospital — Philadelphia
• … and 2 more centers

Germany · 7 centers

• Charite- Universitätsklinikum Berlin — Berlin
• Universitätsklinikum der Ruhr-Universität Bochum — Bochum
• Universitätsklinikum Hamburg-Eppendorf — Hamburg
• Medizinische Hochscule Hannover — Hanover
• Friedrich-Schiller-Universität Jena — Jena
• Universitätsklinik Magdeburg — Magdeburg
• Technical University Munich, Klinikum Rechts der Isar — Munich

United Kingdom · 2 centers

• Cambridge University Hospital, Addenbrooke's Hospital — Cambridge
• King's College Hospital — London

Australia · 1 center

• Westmead Institute for Medical Research — Westmead

Brazil · 1 center

• Hospital Israelita Albert Einstein — São Paulo

Saudi Arabia · 1 center

• King's Faisal Specialist Hospital and Research Center — Riyadh

Publications

• Gilhus NE, Tzartos S, Evoli A, Palace J, Burns TM, Verschuuren JJGM. Myasthenia gravis. Nat Rev Dis Primers. 2019 May 2;5(1):30. doi: 10.1038/s41572-019-0079-y. PMID 31048702

Identifiers

NCT: NCT06193889 · KYSA-6 · KYV101-006

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗