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

Myasthenia Gravis Clinical Trial

Official title:

A Phase 2, Open-Label, Multicentre Study of KYV-101, an Autologous Fully Human Anti-CD19 Chimeric Antigen Receptor T-cell (CD19 CAR T) Therapy, in Subjects With Refractory Generalized Myasthenia Gravis (KYSA-6)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06193889
• Other study ID #: KYV101-006
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: March 2024
• Est. completion date: May 2027

Study information

• Verified date: March 2024
• Source: Kyverna Therapeutics
• Contact: Kyverna Therapeutics, Inc.
• Phone: 510-925-2484
• Email: Medicalmonitor[@]kyvernatx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: May 2027
• Est. primary completion date: May 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Key Inclusion Criteria

1. Diagnosis of MG with presence of autoantibodies to AChR and MuSK

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

Key Exclusion Criteria

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

2. History of allogeneic or autologous stem cell transplant

3. Evidence of active hepatitis B or hepatitis C infection

4. Positive serology for HIV

5. Primary immunodeficiency

6. History of splenectomy

7. History of stroke, seizure, dementia, Parkinson's disease, cerebellar diseases, psychosis, aphasia, and any other neurologic disorder investigator considers would increase the risk for the subject

8. Impaired cardiac function or clinically significant cardiac disease

9. Previous or concurrent malignancy with the following exceptions:

1. Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to screening)

2. In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to screening

3. A primary malignancy which has been completely resected, or treated, and is in complete remission for at least 5 years prior to screening

Related Conditions & MeSH terms

• Generalized Myasthenia Gravis
• Muscle Weakness
• Myasthenia Gravis

Intervention

Biological:
• KYV-101
Anti-CD19 CAR-T cell therapy

Drug:
• Standard lymphodepletion regimen
Standard lymphodepletion regimen

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Kyverna Therapeutics

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of KYV-101 as assessed by incidence of adverse events (AEs) and laboratory abnormalities		Up to 24 months
Primary	Efficacy of KYV-101 via Myasthenia Gravis Activities of Daily Living (MG-ADL) total score		24 weeks
Secondary	Efficacy of KYV-101 via quantitative myasthenia gravis (QMG) score		12, 24, and 52 weeks
Secondary	Efficacy of KYV-101 via Myasthenia Gravis Composite (MGC) score		12, 24, and 52 weeks
Secondary	Disease-related antibodies via levels of anti acetylcholine receptor (anti-AchR)		Up to 2 years
Secondary	Disease-related antibodies via levels of anti muscle-specific tyrosine kinase (anti-MuSK) antibodies		Up to 2 years
Secondary	Disease-related antibodies via levels of anti lipoprotein-related protein 4 (anti-LRP4) antibodies		Up to 2 years
Secondary	Pharmacokinetics (PK) via chimeric antigen receptor positive (CAR-positive) T cell counts		Up to 2 years
Secondary	Pharmacodynamics (PD) via B cell counts		Up to 2 years
Secondary	Pharmacodynamics (PD) via systemic cytokine concentrations		Up to 2 years
Secondary	Immunogenicity (humoral response) of KYV-101 (percentage of participants who develop anti-KYV-101 antibodies by immunoassays)		Up to 2 years