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

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

Study Overview

• Status: Recruiting
• Conditions: Generalized Myasthenia Gravis; Myasthenia Gravis
• Intervention / Treatment: Drug: Standard lymphodepletion regimen; Biological: KYV-101; Drug: Standard of Care Treatment

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).

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Kyverna Therapeutics, Inc.; Phone Number: 510-925-2484; Email: Clinicaltrials@kyvernatx.com

Study Locations

• Australia
  • Westmead, Australia
    • Recruiting
    • Westmead Institute for Medical Research
    • Contact: Study Coordinator
• Brazil
  • São Paulo, Brazil
    • Recruiting
    • Hospital Israelita Albert Einstein
    • Contact: Study Coordinator
• Germany
  • Berlin, Germany
    • Recruiting
    • Charite- Universitätsklinikum Berlin
    • Contact: Study Coordinator
  • Bochum, Germany
    • Recruiting
    • Universitätsklinikum der Ruhr-Universität Bochum
    • Contact: Study Coordinator
  • Hamburg, Germany
    • Recruiting
    • Universitätsklinikum Hamburg-Eppendorf
    • Contact: Study Coordinator
  • Hanover, Germany
    • Recruiting
    • Medizinische Hochscule Hannover
    • Contact: Study Coordinator
  • Jena, Germany
    • Recruiting
    • Friedrich-Schiller-Universität Jena
    • Contact: Study Coordinator
  • Magdeburg, Germany
    • Recruiting
    • Universitätsklinik Magdeburg
    • Contact: Study Coordinator
  • Munich, Germany
    • Recruiting
    • Technical University Munich, Klinikum Rechts der Isar
    • Contact: Study Coordinator
• United States
  • California
    • Orange, California, United States, 92868
      • Recruiting
      • University of California, Irvine
      • Contact: Study Coordinator
    • Palo Alto, California, United States, 94305
      • Recruiting
      • Stanford University Medical Center
      • Contact: Study Coordinator
  • Florida
    • Miami, Florida, United States, 33149
      • Recruiting
      • University of Miami
      • Contact: Study Coordinator
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University Health
      • Contact: Study Coordinator
  • Missouri
    • Columbia, Missouri, United States, 65212
      • Recruiting
      • University of Missouri
      • Contact: Study Coordinator
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University Hospital
      • Contact: Study Coordinator
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Houston Methodist Hospital
      • Contact: Study Coordinator
  • Utah
    • Murray, Utah, United States, 84107
      • Recruiting
      • Intermountain Medical Center
      • Contact: Study Coordinator

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KYV-101 CAR-T cells with lymphodepletion conditioning; Phase 2: Dosing with KYV-101 CAR-T cells	Drug: Standard lymphodepletion regimen; Standard lymphodepletion regimen; Other Names: Cyclophosphamide; Fludarabine; Biological: KYV-101; Anti-CD19 CAR-T cell therapy
Experimental: KYV-101 Treatment; Phase 3	Drug: Standard lymphodepletion regimen; Standard lymphodepletion regimen; Other Names: Cyclophosphamide; Fludarabine; Biological: KYV-101; Anti-CD19 CAR-T cell therapy
Active Comparator: Standard of Care; Phase 3 Optional crossover to receive KYV-101 Treatment after 24 weeks	Drug: Standard lymphodepletion regimen; Standard lymphodepletion regimen; Other Names: Cyclophosphamide; Fludarabine; Biological: KYV-101; Anti-CD19 CAR-T cell therapy; Drug: Standard of Care Treatment; Standard of Care Medications Optional Crossover to receive KYV-101 treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Efficacy of KYV-101 via Myasthenia Gravis Activities of Daily Living (MG-ADL) change from baseline (Phase 2)	24 weeks
Incidence and severity of adverse events (AEs) and laboratory abnormalities (Phase 2)	18 months
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 (Phase 3)	24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
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
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)	24 weeks
Incidence and severity of adverse events (AEs) and laboratory abnormalities (Phase 3)	18 months

Collaborators and Investigators

• Sponsor: Kyverna Therapeutics
• Investigators: Study Director: MD, Kyverna Therapeutics, Inc.

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: October 11, 2023
• First Submitted That Met QC Criteria: December 21, 2023
• First Posted (Actual): January 5, 2024

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: MG; cellular therapy; myasthenia gravis; autoimmune disease; KYV-101; anti-CD19 CAR-T Therapy; KYSA-6; KYV101-006; mivocabtagene autoleucel; miv-cel
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Neuromuscular Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Neurodegenerative Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Myasthenia Gravis; Autoimmune Diseases; Organic Chemicals; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclophosphamide; fludarabine
• Other Study ID Numbers: KYSA-6; KYV101-006 (Other Identifier: Kyverna Therapeutics)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No