Descartes-08 for autoantibody myositis (antisynthetase syndrome and dermatomyositis)

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

This trial will test whether Descartes-08, an mRNA CAR-T therapy targeting BCMA, can help adults with autoantibody-driven myositis such as antisynthetase syndrome or dermatomyositis who have not responded to standard treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Cartesian Therapeutics (Industry-sponsored)
• Drugs / interventions: chimeric antigen receptor
• Locations: 2 sites (Chapel Hill, North Carolina and 1 other locations)
• Trial ID: NCT07391605 on ClinicalTrials.gov

What this trial studies

This randomized, double-blind, placebo-controlled phase 2 trial gives participants an autologous mRNA CAR-T product (Descartes-08) engineered to target B-cell maturation antigen (BCMA) to deplete autoantibody-producing B cells. Adults with dermatomyositis or antisynthetase syndrome with muscle and/or skin involvement who are refractory or intolerant to standard therapy and on stable immunosuppression are randomized to receive Descartes-08 or placebo with follow-up for efficacy and safety. Primary measures include clinical improvement scores such as Total Improvement Score and skin disease activity by CDASI, along with safety and tolerability assessments. Procedures include leukapheresis to collect autologous T cells, infusion of the mRNA CAR-T product, and serial clinic visits at sites in North Carolina and Texas.

Who should consider this trial

Good fit: Ideal candidates are adults with dermatomyositis or antisynthetase syndrome who have muscle or skin involvement, have failed or cannot tolerate standard therapies, are on stable immunosuppression, and meet organ function and safety criteria for leukapheresis and cell therapy.

Not a fit: Patients with isolated interstitial lung disease without muscle or skin involvement, those with severe irreversible muscle damage or advanced weakness (for example, wheelchair-bound), or those with inadequate hematologic, hepatic, renal, or pulmonary function are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, the therapy could reduce autoantibody-producing B cells and improve muscle and skin symptoms in patients who have not responded to existing treatments.

How similar studies have performed: BCMA-targeted CAR-T therapies have been highly effective in B-cell malignancies and early case reports and small studies suggest B-cell targeting can help some autoimmune conditions, but applying mRNA CAR-T to myositis is a novel and still experimental approach.

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.

Where this trial is running

Chapel Hill, North Carolina and 1 other locations

• T13 — Chapel Hill, North Carolina, United States (Recruiting)
• T23 — Austin, Texas, United States (Recruiting)

Study contacts

• Study coordinator: Vera MD

Conditions Antisynthetase Syndrome; MYOSITIS; DESCARTES-08; MRNA CAR-T; TOTAL IMPROVEMENT SCORES; CDASI