Clinical trial NCT06193889: KYSA-6: A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy, in Subjects With Refractory Generalized Myasthenia Gravis
Official title: KYSA-6: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Myasthenia Gravis
Generalized Myasthenia Gravis
Keywords: KYV-101
myasthenia gravis
autoimmune disease
anti-CD19 CAR-T Therapy
cellular therapy
MG
KYSA-6
KYV101-006
Lead sponsor: Kyverna Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-01-05
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A Study of the Anti-CD 19 Chimeric Antigen Receptor T Cell Therapy for Subjects 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, a fully human anti-CD19 CAR T-cell therapy, will be investigated in adult subjects with myasthenia gravis (MG).

Eligibility criteria: 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\*
3. MG-Activities of Daily Living (MG-ADL) total score of ≥6 at screening and at pre-dose baseline
4. Failed treatment over 1 year or more with 2 or more immunosuppressive/immunomodulatory therapies or; failed at least 1 immunosuppressive therapy and required chronic plasmapheresis, or IVIG to control symptoms\*\*
5. On a stable dose of glucocorticoids and/or other immunotherapies for ≥1 month prior to screening. For azathioprine, being on a stable dose for ≥2 months prior to screening is require
6. No change in dose of acetylcholinesterase inhibitors for ≥2 weeks prior to screening
7. No use of IV Igor plasma exchange (PLEX) within 4 weeks of pre-dose baseline

(\*) For Germany Sites: Myasthenia Gravis Foundation of America (MGFA) Class III-IV. Patients with disease classified as MGFA Class IIB may be included if the patient requires continuous treatment with IVIG or PLEX to be maintained at MGFA class IIB.

(\*\*) For Germany Sites: In the preceding 2 years failed two monoclonal antibodies with different mechanisms of action - or - failed at least 1 monoclonal antibody and required chronic plasmapheresis, or IVIg to control symptoms. Patients are required to have failed two different monoclonal antibodies as treatment for the preceding 1 to 2 years.

Key Exclusion Criteria

1. Impaired cardiac function or clinically significant cardiac disease including:

   1. Unstable angina or myocardial infarction or coronary artery bypass graft within 6 months prior to apheresis
   2. New York Heart Association stage III or IV congestive heart failure
   3. History of clinically significant cardiac arrhythmia (e.g., ventricular tachycardia, QTc prolongation, and/or torsades de pointes), complete left bundle branch block, high-grade atrioventricular block
   4. History of severe nonischaemic cardiomyopathy
   5. Left ventricular ejection fraction (LVEF) \<45% as assessed by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan (performed ≤8 weeks of apheresis)
2. Serious and/or uncontrolled medical condition and severity of the underlying MG disease activity that, in the investigator's judgment, would cause unacceptable safety risk, interfere with study procedures or results, or compromise compliance with the protocol, such as:

   1. Active, uncontrolled, viral, bacterial, or systemic fungal infection (including human T -cell lymphotropic virus \[HTLV\], human polyomavirus 2 \[JC virus\], or syphilis); or recent history of repeated infections
   2. Clinical evidence of dementia or altered mental status
   3. Recent thromboembolic event
   4. On anti-coagulation agents that would be unsafe to transiently hold for medical procedures

Primary outcomes:
measure: Incidence of adverse events (AEs) and laboratory abnormalities
timeFrame: 2 years
measure: Efficacy of KYV-101 via Myasthenia Gravis Activities of Daily Living (MG-ADL) total score
timeFrame: 24 weeks
Secondary outcomes:
measure: Efficacy of KYV-101 via quantitative myasthenia gravis (QMG) score
timeFrame: 12, 24, and 52 weeks
measure: Efficacy of KYV-101 via Myasthenia Gravis Composite (MGC) score
timeFrame: 12, 24, and 52 weeks
measure: Disease-related antibodies via levels of anti acetylcholine receptor (anti-AchR)
timeFrame: Up to 2 years
measure: Disease-related antibodies via levels of anti muscle-specific tyrosine kinase (anti-MuSK) antibodies
timeFrame: Up to 2 years
measure: Disease-related antibodies via levels of anti lipoprotein-related protein 4 (anti-LRP4) antibodies
timeFrame: Up to 2 years
measure: To characterize Pharmacokinetics (PK) via chimeric antigen receptor positive (CAR-positive) T cell counts
timeFrame: Up to 2 years
measure: To characterize Pharmacodynamics (PD) via B cell counts
timeFrame: Up to 2 years
measure: To characterize Pharmacodynamics (PD) via systemic cytokine concentrations
timeFrame: Up to 2 years
measure: To evaluate the Immunogenicity (humoral response) of KYV-101 (percentage of participants who develop anti-KYV-101 antibodies by immunoassays)
timeFrame: Up to 2 years
measure: To assess PRO (Patient Outcome Rate) after infusion of KYV-101
timeFrame: Up to 2 years
measure: To assess PRO (Patient Reported Outcome) after infusion of KYV-101
timeFrame: Up to 2 years
measure: To assess PRO (Patient Reported Outcome) after infusion of KYV-101
timeFrame: Up to 2 years
measure: To assess PRO (Patient Reported Outcome) after infusion of KYV-101
timeFrame: Up to 2 years
measure: To assess PRO (Patient Reported Outcome) after infusion of KYV-101
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California, Irvine
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Berlin
country: Germany
facility: Charite- Universitätsklinikum Berlin
city: Bochum
country: Germany
facility: Universitätsklinikum der Ruhr-Universität Bochum
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Hannover
country: Germany
facility: Medizinische Hochscule Hannover
city: Jena
country: Germany
facility: Friedrich-Schiller-Universität Jena
city: Magdeburg
country: Germany
facility: Universitätsklinik Magdeburg
Study officials:
affiliation: Kyverna Therapeutics, Inc.
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.