Descartes-08 in Autoantibody Myositis

Official title

A Randomized Double-Blind Placebo-Controlled Study to Evaluate Efficacy, Safety, and Tolerability of Descartes-08 in Patients With Dermatomyositis and Antisynthetase Syndrome

Overview

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).

Interventions

• Drug Descartes-08
  Autologous T-cells expressing a chimeric antigen receptor (CAR) directed to B-Cell maturation antigen (BCMA)
• Other Placebo
  Plasma-Lyte

Primary outcome measures

• Major improvement of 2016 ACR/EULAR Total Improvement score [Time frame: 24 weeks]

Eligibility criteria

Inclusion criteria

• Confirmed diagnosis of one of the following:

Dermatomyositis (DM): Probability score ≥55% on the 2017 EULAR/ACR (European Alliance of Associations of Rheumatology/ American College of Rheumatology) criteria for classification of dermatomyositis (corresponding to diagnosis of 'probable or definite' DM). OR Antisynthetase Syndrome (ASyS): Diagnosis based on ACR/EULAR Classification Criteria (1)."

• Participants must have dermatomyositis or antisynthetase syndrome with muscle and/or skin involvement.
• Refractory or intolerance to standard therapy.
• Stable background immunosuppressive therapy for ≥8 weeks.
• Adequate hematologic, renal, hepatic, and pulmonary function (SpO₂ ≥92% on room air).
• Informed consent, compliance with visits, contraception, and vaccinations required.

Exclusion criteria

• Isolated interstitial lung disease (ILD) without muscle or skin involvement

• Severe irreversible muscle damage or advanced weakness (e.g., wheelchair-bound).
• Interstitial lung disease (ILD) requiring oxygen, severe pulmonary impairment (FVC ≤45%, DLCO ≤40%), or pulmonary hypertension.
• Other inflammatory myopathies (PM, IMNM, IBM, cancer- or drug-induced myositis, overlap myositis except Sjögren's).
• Other severe neuromuscular, cardiac, pulmonary, or systemic autoimmune diseases requiring immunosuppression.
• Significant uncontrolled chronic illnesses or psychiatric conditions interfering with participation.
• Pregnancy or lactation.
• Recent use of prohibited immunosuppressants/biologics or investigational agents (per washout periods).
• Live vaccination within 4 weeks.
• History of primary immunodeficiency, organ or bone marrow transplant.
• Active or uncontrolled infections: HBV, HCV, HIV, tuberculosis, or recurrent/severe infections.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 2 centers

• T13 — Chapel Hill
• T23 — Austin

Publications

• Fedak RR, Ruggerie RN, Shan Y, Curvino EJ, de Sousa JF, Daniel S, Ngo-Casi M, Kamboh H, Vu T, Durmus H, Mozaffar T, Howard JF Jr, English EP, Benson A, Duvernay MT, Singer MS, Kalayoglu MV, Brunn C, Bodansky A, Anderson MS, DeRisi JL, Garcia ST, Yu DJL, Zorn KC, Kurtoglu M, Miljkovic MD, Stewart CA, Jewell CM; MG-001 Study Team. BCMA-directed mRNA CAR-T cell therapy for myasthenia gravis: explorat PMID 41514039

Identifiers

NCT: NCT07391605 · RNAC-TRITON-08

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗