Treatment for severe autoimmune rheumatic diseases using a new cell therapy

A Phase 1, Open-Label Study to Evaluate the Safety and Tolerability of a Combination Autologous CD19 CAR T Cell Therapy (SYNCAR-001 + STK-009) in Subjects With Severe, Refractory Systemic Autoimmune Rheumatic Disease

This study is testing a new cell therapy combined with a special medication to see if it can help people with severe autoimmune rheumatic diseases feel better.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Synthekine (Industry-sponsored)
• Drugs / interventions: CAR T, CAR-T, chimeric antigen receptor, chemotherapy
• Locations: 5 sites (Scottsdale, Arizona and 4 other locations)
• Trial ID: NCT06544330 on ClinicalTrials.gov

What this trial studies

This phase 1 study evaluates the safety and efficacy of SYNCAR-001, a CD19-directed CAR-T cell therapy, combined with STK-009, an engineered IL-2 cytokine, in patients with severe, refractory systemic autoimmune rheumatic diseases. The study involves administering a single dose of SYNCAR-001 followed by multiple doses of STK-009 without prior conditioning chemotherapy. It employs a 3+3 design for dose escalation, followed by dose expansion at the recommended phase 2 dose. The goal is to assess how well this combination therapy works in treating conditions like systemic lupus erythematosus and systemic sclerosis.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with severe, refractory systemic lupus erythematosus or systemic sclerosis.

Not a fit: Patients with rapidly progressive glomerulonephritis or end-stage renal failure may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from severe autoimmune rheumatic diseases that are resistant to current therapies.

How similar studies have performed: While CAR-T therapies have shown promise in hematological malignancies, this approach in autoimmune diseases is relatively novel and has not been extensively tested.

Eligibility criteria

General Inclusion Criteria:

Age ≥18 years at screening.

SLE Inclusion Criteria:

1. Clinical diagnosis of SLE according to the 2019 European League Rheumatism EULAR/ACR classification criteria.
2. Subject must be positive for at least one of the following at screening: Anti-dsDNA (above the upper limit of normal \[ULN\]); or anti-Sm (above the ULN); or anti-Chromatin (above the ULN).
3. Subjects with active, severe, non-renal SLE or subjects with active proliferative LN

SSc Inclusion Criteria:

1. Classified as SSc according to the ACR/EULAR classification criteria.
2. Diffuse cutaneous SSc (dcSSc) or SSc-associated ILD (SSc-ILD; significant or progressive).

General Exclusion Criteria:

1. History of or active central nervous system manifestations of autoimmune disease.
2. Prior treatment with anti-CD19 adoptive T cell therapy, or any prior gene therapy product (e.g., CAR T cell therapy).

SLE Exclusion Criteria:

1. Rapidly progressive glomerulonephritis.
2. End stage renal failure requiring dialysis or most recent renal biopsy with purely chronic lesions (Class III\[C\], IV-S\[C\], or IV-G\[C\]) if isolated renal disease.

SSc Exclusion Criteria:

1. FVC \<50% of predicted or DLCO \<40% of predicted.
2. Pulmonary arterial hypertension (PAH) requiring PAH-specific treatment.

Other protocol-defined criteria apply.

Where this trial is running

Scottsdale, Arizona and 4 other locations

• HonorHealth Research Institute — Scottsdale, Arizona, United States (Recruiting)
• Hackensack University Medical Center — Hackensack, New Jersey, United States (Recruiting)
• Feinstein Institutes for Medical Research — Manhasset, New York, United States (Recruiting)
• The Cleveland Clinic Foundation — Cleveland, Ohio, United States (Recruiting)
• Ohio State University Wexner Medical Center — Columbus, Ohio, United States (Recruiting)

Study contacts

• Study coordinator: Clinical Operations

Conditions Systemic Lupus Erythematosus; Lupus Nephritis; Systemic Sclerosis; CAR T; CD19-CAR T; Chimeric antigen receptor; IL-2