Lupus Nephritis, Systemic Lupus Erythematosus, Systemic Sclerosis
Conditions
Keywords
CAR T, CD19-CAR T, Chimeric antigen receptor, IL-2
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).
Interventions
DRUGSYNCAR-001
SYNCAR-001 is an autologous CD19-targeted CAR-T with co-expression of hoRb
DRUGSTK-009
STK-009 is a human orthogonal IL-2 cytokine selective for SYNCAR-001 CAR-T cells expressing hoRb
Sponsors
Synthekine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Outcome results
None listed