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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Systemic Lupus Erythematosus; Systemic Sclerosis; Lupus Nephritis
• Intervention / Treatment: Drug: SYNCAR-001; Drug: STK-009

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 Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Institute
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • Manhasset, New York, United States, 11030
      • Feinstein Institutes for Medical Research
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • Ohio State University Wexner Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: SYNCAR-001 + 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.

Drug: SYNCAR-001; SYNCAR-001 is an autologous CD19-targeted CAR-T with co-expression of hoRb; Drug: STK-009; STK-009 is a human orthogonal IL-2 cytokine selective for SYNCAR-001 CAR-T cells expressing hoRb

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete renal response rate (CRR)	Lupus Nephritis only. CRR will be defined as a UPCR < 0.5 and no eGFR decrease > 15% from baseline.	Up to 96 weeks after SYNCAR-001 infusion
Remission rate per Definition of Remission in SLE (DORIS)	For SLE only	Up to 96 weeks after SYNCAR-001 infusion
Lupus Low Disease Activity State (LLDAS) attainment rate	For SLE only	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.	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.	Up to 96 weeks after SYNCAR-001 infusion
Change over time in levels of SLE and SSc serum autoantibodies		Up to 96 weeks after SYNCAR-001 infusion
Change over time in Modified Rodnan Skin Score (mRSS)	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)	Up to 96 weeks after SYNCAR-001 infusion
Proportion of subjects achieving revised Composite Response Index in Systemic Sclerosis (rCRISS-25) criteria	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	Up to 96 weeks after SYNCAR-001 infusion
Proportion of subjects achieving rCRISS-25 criteria with no immunosuppressive therapy.	Systemic Sclerosis only	Up to 96 weeks after SYNCAR-001 infusion
Change over time in pulmonary function tests	Systemic Sclerosis only. Pulmonary function tests include % predicted FVC (Forced Vital Capacity) and % predicted DLCO (Diffusing capacity of the lung for carbon monoxide)	Up to 96 weeks after SYNCAR-001 infusion
Change over time in high resolution computed tomography of the chest for subjects with interstitial lung disease.	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	Up to 96 weeks after SYNCAR-001 infusion

Collaborators and Investigators

• Sponsor: Synthekine

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2041

Study Registration Dates

• First Submitted: July 25, 2024
• First Submitted That Met QC Criteria: August 6, 2024
• First Posted (Actual): August 9, 2024

Study Record Updates

• Last Update Posted (Estimated): November 4, 2025
• Last Update Submitted That Met QC Criteria: October 31, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: IL-2; CAR T; Chimeric antigen receptor; CD19-CAR T
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin Diseases; Glomerulonephritis; Nephritis; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis; Scleroderma, Systemic
• Other Study ID Numbers: STK-009-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No