Clinical trial NCT06544330: A Phase 1 Study of SYNCAR-001 + STK-009 Without Conditioning Chemotherapy (Lymphodepletion) in Subjects With Severe, Refractory Systemic Autoimmune Rheumatic Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Systemic Lupus Erythematosus
Lupus Nephritis
Systemic Sclerosis
Keywords: CAR T
CD19-CAR T
Chimeric antigen receptor
IL-2
Lead sponsor: Synthekine
Sponsor class: INDUSTRY
First posted: 2024-08-09
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase 1 study of SYNCAR-001 + STK-009 in patients with severe, refractory systemic autoimmune rheumatic disease.

Detailed description: SYNCAR-001 + STK-009 is a 2-component human orthogonal (ho) IL-2 receptor-ligand cell therapy consisting of (1) SYNCAR-001, a CD19-directed chimeric antigen receptor T cell (CAR-T) co-expressing an engineered IL-2 beta receptor (hoRb); and (2) STK-009, an engineered pegylated IL-2 cytokine (hoIL-2) selective for hoRb. This study is being conducted to evaluate the safety and efficacy of a single dose of SYNCAR-001 followed by multiple subcutaneously administered doses of STK-009. No conditioning chemotherapy (lymphodepletion) will be administered. The study will follow a 3+3 design during dose escalation followed by dose expansion at the recommended phase 2 dose (RP2D).

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.

Primary outcomes:
measure: Dose-Limiting Toxicities (DLTs)
timeFrame: Up to 28 days after SYNCAR-001 infusion
measure: Adverse Events
timeFrame: Up to 96 weeks after SYNCAR-001 infusion
Secondary outcomes:
measure: Remission rate per Definition of Remission in SLE (DORIS)
timeFrame: Up to 96 weeks after SYNCAR-001 infusion
measure: Lupus Low Disease Activity State (LLDAS) attainment rate
timeFrame: Up to 96 weeks after SYNCAR-001infusion
measure: Change over time in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)
timeFrame: Up to 96 weeks after SYNCAR-001 infusion
measure: Change over time in British Isles Lupus Activity Group (BILAG) score
timeFrame: Up to 96 weeks after SYNCAR-001 infusion
measure: Change over time in levels of SLE and SSc serum autoantibodies
timeFrame: Up to 96 weeks after SYNCAR-001 infusion
measure: Complete renal response rate (CRR)
timeFrame: Up to 96 weeks after SYNCAR-001 infusion
measure: Change over time in Modified Rodnan Skin Score (mRSS)
timeFrame: Up to 96 weeks after SYNCAR-001 infusion
measure: Proportion of subjects achieving revised Composite Response Index in Systemic Sclerosis (rCRISS-25) criteria
timeFrame: Up to 96 weeks after SYNCAR-001 infusion
measure: Proportion of subjects achieving rCRISS-25 criteria with no immunosuppressive therapy.
timeFrame: Up to 96 weeks after SYNCAR-001 infusion
measure: Change over time in pulmonary function tests
timeFrame: Up to 96 weeks after SYNCAR-001 infusion
measure: Change over time in high resolution computed tomography of the chest for subjects with interstitial lung disease.
timeFrame: Up to 96 weeks after SYNCAR-001 infusion
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institute
state: Arizona
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Manhasset
country: United States
facility: Feinstein Institutes for Medical Research
state: New York
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
Study officials:
References: