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NCT Number: NCT06544330

A Phase 1 Study of SYNCAR-001 + STK-009 Without Conditioning Chemotherapy (Lymphodepletion) 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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Systemic Lupus Erythematosus Autoimmune Diseases Connective Tissue Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Glomerulonephritis Immune System Diseases Kidney Diseases Lupus Erythematosus, Systemic Lupus Nephritis Male Urogenital Diseases Nephritis Scleroderma, Systemic Skin Diseases Skin and Connective Tissue Diseases Systemic Sclerosis Urogenital Diseases Urologic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

HonorHealth Research Institute, Scottsdale, Arizona, United States

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About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

General Inclusion Criteria:

Age ≥18 years at screening.

SLE Inclusion Criteria:

  • Clinical diagnosis of SLE according to the 2019 European League Rheumatism EULAR/ACR classification criteria.
  • 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).
  • Subjects with active, severe, non-renal SLE or subjects with active proliferative LN

SSc Inclusion Criteria:

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

General Exclusion Criteria:

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

SLE Exclusion Criteria:

  • Rapidly progressive glomerulonephritis.
  • 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:

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

Other protocol-defined criteria apply.

Treatment and study plan

SYNCAR-001

Drug

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

STK-009

Drug

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

Primary outcomes

  1. Dose-Limiting Toxicities (DLTs)

    Time frame: 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.

  2. Adverse Events

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

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

Secondary outcomes

  1. Remission rate per Definition of Remission in SLE (DORIS)

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

    For SLE only

  2. Lupus Low Disease Activity State (LLDAS) attainment rate

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

    For SLE only

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

    Time frame: 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.

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

    Time frame: 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.

  5. Change over time in levels of SLE and SSc serum autoantibodies

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

  6. Complete renal response rate (CRR)

    Time frame: 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.

  7. Change over time in Modified Rodnan Skin Score (mRSS)

    Time frame: 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)

  8. Proportion of subjects achieving revised Composite Response Index in Systemic Sclerosis (rCRISS-25) criteria

    Time frame: 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

  9. Proportion of subjects achieving rCRISS-25 criteria with no immunosuppressive therapy.

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

    Systemic Sclerosis only

  10. Change over time in pulmonary function tests

    Time frame: 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)

  11. Change over time in high resolution computed tomography of the chest for subjects with interstitial lung disease.

    Time frame: 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

Sponsors and collaborators

Lead sponsor

Synthekine

Industry

Registry information

Official study 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

Important dates

Study start
2025
Primary completion
2028
Study completion
2041
First posted
Aug 9, 2024
Registry last updated
Jul 10, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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