A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy, in Subjects With Refractory Generalized Myasthenia Gravis

Phase 2

Recruiting

• Conditions: Refractory generalized myasthenia gravis

• Registration Number: 2023-509892-17-00
• Lead Sponsor: Kyverna Therapeutics Inc.

Brief Summary

To characterize the safety and tolerability and to evaluate the efficacy of KYV-101

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).

Study Timeline

• Study First Posted: 2024-05-13
• Last Update Posted: 2025-06-13

Recruitment & Eligibility

• Status: Ongoing, recruiting
• Sex: Not specified
• Target Recruitment: 10

Inclusion Criteria

Diagnosis of MG with presence of autoantibodies to AChR and MuSK

Myasthenia Gravis Foundation of America (MGFA) Class IIB-IV

Exclusion Criteria

Prior treatment with cellular immunotherapy (CAR-T) or gene therapy product directed at any target

History of allogeneic or autologous stem cell transplant

Evidence of active hepatitis B or hepatitis C infection

Positive serology for HIV

Primary immunodeficiency

History of splenectomy

History of stroke, seizure, dementia, Parkinson’s disease, coordination movement disorder, cerebellar diseases, psychosis, paresis, aphasia, and any other neurologic disorder investigator considers would increase the risk for the subject

Impaired cardiac function or clinically significant cardiac disease

Previous or concurrent malignancy with the following exceptions: a. Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to screening). b. In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to screening. c. A primary malignancy which has been completely resected, or treated, and is in complete remission for at least 5 years prior to screening.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Incidence and severity of AEs and laboratory abnormalities.		Incidence and severity of AEs and laboratory abnormalities.
MG-ADL at 24 weeks.		MG-ADL at 24 weeks.

Secondary Outcome Measures

Name	Time	Method
QMG score at 12, 24, and 52 weeks		QMG score at 12, 24, and 52 weeks
MGC score at 12, 24, and 52 weeks		MGC score at 12, 24, and 52 weeks
Change in anti-AChR, anti-MuSK, and anti-LRP4 antibodies over time		Change in anti-AChR, anti-MuSK, and anti-LRP4 antibodies over time
CAR-positive T-cell counts, CAR transgene level, B-cell counts over time, systemic cytokine concentrations		CAR-positive T-cell counts, CAR transgene level, B-cell counts over time, systemic cytokine concentrations
Presence of anti-KYV-101 antibodies		Presence of anti-KYV-101 antibodies
Change from baseline in: MGQOL15r, MGFA-PIS, Neuro-QOL Fatigue Scale, and EQ-5D		Change from baseline in: MGQOL15r, MGFA-PIS, Neuro-QOL Fatigue Scale, and EQ-5D

Trial Locations

Locations (6)

St. Josef-Hospital; 🇩🇪 Bochum, Germany

Universitaetsklinikum Jena KöR; 🇩🇪 Jena, Germany

Charite Universitaetsmedizin Berlin KöR; 🇩🇪 Berlin, Germany

Universitaetsklinikum Magdeburg AöR; 🇩🇪 Magdeburg, Germany

Medizinische Hochschule Hannover; 🇩🇪 Hanover, Germany

University Medical Center Hamburg-Eppendorf; 🇩🇪 Hamburg, Germany

St. Josef-Hospital

🇩🇪Bochum, Germany

Jeremias Motte

Site contact

+492345096425

jeremias.motte@ruhr-uni-bochum.de