A Phase 1 Study of SYNCAR-001 + STK-009 Without Conditioning Chemotherapy (Lymphodepletion) in Subjects With Severe, Refractory Systemic Autoimmune Rheumatic Disease

Phase 1Active Not RecruitingNCT06544330

Synthekine48 enrolled

Overview

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

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).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Systemic Lupus Erythematosus Lupus Nephritis Systemic Sclerosis

Interventions

SYNCAR-001DRUG

SYNCAR-001 is an autologous CD19-targeted CAR-T with co-expression of hoRb

STK-009DRUG

STK-009 is a human orthogonal IL-2 cytokine selective for SYNCAR-001 CAR-T cells expressing hoRb

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (5)

HonorHealth Research Institute

Scottsdale, Arizona, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Feinstein Institutes for Medical Research

Manhasset, New York, United States

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Outcomes

Primary Outcomes

Dose-Limiting Toxicities (DLTs)

Incidence of adverse events (AEs) meeting protocol defined DLT criteria in the dose escalation phase of the study.

Time frame: Up to 28 days after SYNCAR-001 infusion

Adverse Events

Incidence and severity of AEs including treatment-emergent AEs and serious AEs.

Time frame: Up to 96 weeks after SYNCAR-001 infusion

Secondary Outcomes

Remission rate per Definition of Remission in SLE (DORIS)

For SLE only

Time frame: Up to 96 weeks after SYNCAR-001 infusion

Lupus Low Disease Activity State (LLDAS) attainment rate

For SLE only

Time frame: Up to 96 weeks after SYNCAR-001infusion

Change over time in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)

For SLE only. The SLEDAI-2K assessment consists of 24 items with a total score of 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores indicating increased disease activity.

Time frame: Up to 96 weeks after SYNCAR-001 infusion

Change over time in British Isles Lupus Activity Group (BILAG) score

For SLE only. The BILAG instrument assesses 97 clinical signs, symptoms, and laboratory parameters across 9 organ system domains related to SLE. BILAG scoring represents: A=severe disease, B=moderate disease, C=stable mild disease, D=inactive but previously active disease, E=never involved.

Time frame: Up to 96 weeks after SYNCAR-001 infusion

Change over time in levels of SLE and SSc serum autoantibodies

Data from ClinicalTrials.gov

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