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

Phase 1

Recruiting

• Conditions: Systemic Lupus Erythematosus; Lupus Nephritis; Systemic Sclerosis
• Interventions: Drug: SYNCAR-001; Drug: STK-009

• Registration Number: NCT06544330
• Lead Sponsor: Synthekine

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).

Study Timeline

• Study First Submitted: 2024-07-25
• Study First Submitted QC: 2024-08-06
• Study First Posted: 2024-08-09
• Status Verified: 2025-04
• Study Start: 2025-04-29
• Last Update Submitted: 2025-04-29
• Last Update Posted: 2025-05-02
• Primary Completion: 2028-04
• Study Completion: 2041-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 48

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SYNCAR-001 + STK-009	SYNCAR-001	Dose escalation: A single fixed dose of autologous SYNCAR-001 CAR-T intravenously (IV) will be administered in combination with ascending doses of STK-009 subcutaneously (SC) in non-lymphodepleted patients. Dose expansion: A single fixed dose of autologous SYNCAR-001 CAR-T IV will be administered in combination with STK-009 SC at the RP2D in non-lymphodepleted patients.
SYNCAR-001 + STK-009	STK-009	Dose escalation: A single fixed dose of autologous SYNCAR-001 CAR-T intravenously (IV) will be administered in combination with ascending doses of STK-009 subcutaneously (SC) in non-lymphodepleted patients. Dose expansion: A single fixed dose of autologous SYNCAR-001 CAR-T IV will be administered in combination with STK-009 SC at the RP2D in non-lymphodepleted patients.

Primary Outcome Measures

Name	Time	Method
Dose-Limiting Toxicities (DLTs)	Up to 28 days after SYNCAR-001 infusion	Incidence of adverse events (AEs) meeting protocol defined DLT criteria in the dose escalation phase of the study.
Adverse Events	Up to 96 weeks after SYNCAR-001 infusion	Incidence and severity of AEs including treatment-emergent AEs and serious AEs.

Secondary Outcome Measures

Name	Time	Method
Remission rate per Definition of Remission in SLE (DORIS)	Up to 96 weeks after SYNCAR-001 infusion	For SLE only
Lupus Low Disease Activity State (LLDAS) attainment rate	Up to 96 weeks after SYNCAR-001infusion	For SLE only
Change over time in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)	Up to 96 weeks after SYNCAR-001 infusion	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.
Change over time in British Isles Lupus Activity Group (BILAG) score	Up to 96 weeks after SYNCAR-001 infusion	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.
Change over time in levels of SLE and SSc serum autoantibodies	Up to 96 weeks after SYNCAR-001 infusion
Complete renal response rate (CRR)	Up to 96 weeks after SYNCAR-001 infusion	Lupus Nephritis only. CRR will be defined as a UPCR \< 0.5 and no eGFR decrease \> 15% from baseline.
Change over time in Modified Rodnan Skin Score (mRSS)	Up to 96 weeks after SYNCAR-001 infusion	Systemic Sclerosis only. mRSS measures skin thickness and is the sum of scores from 17 surface anatomic areas rated on a 0-3 scale (0=normal skin; 1=mild thickness; 2=moderate thickness; 3=severe thickness with inability to pinch the skin into a fold). mRSS ranges from 0 (best possible outcome) to 51 (worst possible outcome)
Proportion of subjects achieving revised Composite Response Index in Systemic Sclerosis (rCRISS-25) criteria	Up to 96 weeks after SYNCAR-001 infusion	Systemic Sclerosis only. rCRISS-25 is the proportion of patients who improve in ≥ 2/5 ACR CRISS core items by 25% (except 5% for FVC) with no worsening of 1 core item
Proportion of subjects achieving rCRISS-25 criteria with no immunosuppressive therapy.	Up to 96 weeks after SYNCAR-001 infusion	Systemic Sclerosis only
Change over time in pulmonary function tests	Up to 96 weeks after SYNCAR-001 infusion	Systemic Sclerosis only. Pulmonary function tests include % predicted FVC (Forced Vital Capacity) and % predicted DLCO (Diffusing capacity of the lung for carbon monoxide)
Change over time in high resolution computed tomography of the chest for subjects with interstitial lung disease.	Up to 96 weeks after SYNCAR-001 infusion	Systemic Sclerosis only. High resolution computed tomography images of the chest will be scored according to changes in interstitial lung disease using validated qualitative and quantitative methods

Trial Locations

Locations (5)

Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States

Ohio State University Wexner Medical Center; 🇺🇸 Columbus, Ohio, United States

HonorHealth Research Institute; 🇺🇸 Scottsdale, Arizona, United States

Feinstein Institutes for Medical Research; 🇺🇸 Manhasset, New York, United States

The Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States