Descartes-08 in Autoantibody Myositis
Study Description
This is a randomized, double-blind, placebo-controlled phase 2 study to evaluate the efficacy, safety and tolerability of an autologous T-cells expressing a chimeric antigen receptor (CAR) directed to B-Cell maturation antigen (BCMA) in patients with autoantibody-mediated myositis, including antisynthetase syndrome (ASyS) and dermatomyositis (DM).
Eligibility
INCLUSION CRITERIA
- Confirmed diagnosis of one of the following:
a. Dermatomyositis (DM): Probability score of at least 55% under the 2017 EULAR/ACR classification criteria, corresponding to probable or definite DM.
b. Antisynthetase syndrome (ASyS): Diagnosis based on ACR/EULAR classification criteria.
- Dermatomyositis or antisynthetase syndrome with muscle and/or skin involvement.
- Disease refractory to standard therapy or intolerance to standard therapy.
- Stable background immunosuppressive therapy for at least 8 weeks.
- Adequate hematologic, renal, hepatic, and pulmonary function, including oxygen saturation (SpO2) of at least 92% on room air.
- Able to provide informed consent and comply with study visits, contraception requirements, and vaccination requirements.
EXCLUSION CRITERIA
- Isolated interstitial lung disease (ILD) without muscle or skin involvement.
- Severe irreversible muscle damage or advanced weakness, such as being wheelchair-bound.
- Interstitial lung disease requiring oxygen, severe pulmonary impairment (FVC of 45% or less or DLCO of 40% or less), or pulmonary hypertension.
- Other inflammatory myopathies, including polymyositis (PM), immune-mediated necrotizing myopathy (IMNM), inclusion body myositis (IBM), cancer-induced or drug-induced myositis, or overlap myositis other than Sjogren's.
- Other severe neuromuscular, cardiac, pulmonary, or systemic autoimmune diseases requiring immunosuppression.
- Significant uncontrolled chronic illnesses or psychiatric conditions that interfere with study participation.
- Pregnancy or lactation.
- Recent use of prohibited immunosuppressants, biologics, or investigational agents within the applicable protocol-defined washout periods.
- Live vaccination within 4 weeks.
- History of primary immunodeficiency, organ transplant, or bone marrow transplant.
- Active or uncontrolled infections, including hepatitis B (HBV), hepatitis C (HCV), HIV, or tuberculosis, or recurrent/severe infections.