A Phase 2, Open-Label, Multicentre Study of KYV-101 in Subjects with Refractory Generalized Myasthe
Study 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
Diagnosis of MG with presence of autoantibodies to AChR and MuSK
Myasthenia Gravis Foundation of America (MGFA) Class IIB-IV*
MG-Activities of Daily Living (MG-ADL) total score of ≥6 at screening and at pre-dose baseline
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**
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
No change in dose of acetylcholinesterase inhibitors for ≥2 weeks prior to screening
No use of IV Igor plasma exchange (PLEX) within 4 weeks of pre-dose baseline
Key
Impaired cardiac function or clinically significant cardiac disease including:
Unstable angina or myocardial infarction or coronary artery bypass graft within 6 months prior to apheresis
New York Heart Association stage III or IV congestive heart failure
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
History of severe nonischaemic cardiomyopathy
Left ventricular ejection fraction (LVEF) <45% as assessed by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan (performed ≤8 weeks of apheresis)
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
