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
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 48
- 试验地点
- 9
- 主要终点
- Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
This is a phase 1 study of SYNCAR-001 + STK-009 in patients with severe, refractory systemic autoimmune rheumatic disease.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: STK-009 (Drug)
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.
干预措施: SYNCAR-001 (Drug)
结局指标
主要结局
Dose-Limiting Toxicities (DLTs)
时间窗: 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
时间窗: Up to 96 weeks after SYNCAR-001 infusion
Incidence and severity of AEs including treatment-emergent AEs and serious AEs.
次要结局
- Lupus Low Disease Activity State (LLDAS) attainment rate(Up to 96 weeks after SYNCAR-001infusion)
- Remission rate per Definition of Remission in SLE (DORIS)(Up to 96 weeks after SYNCAR-001 infusion)
- Change over time in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)(Up to 96 weeks after SYNCAR-001 infusion)
- Change over time in British Isles Lupus Activity Group (BILAG) score(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)
- Complete renal response rate (CRR)(Up to 96 weeks after SYNCAR-001 infusion)
- Change over time in Modified Rodnan Skin Score (mRSS)(Up to 96 weeks after SYNCAR-001 infusion)
- Proportion of subjects achieving revised Composite Response Index in Systemic Sclerosis (rCRISS-25) criteria(Up to 96 weeks after SYNCAR-001 infusion)
- Proportion of subjects achieving rCRISS-25 criteria with no immunosuppressive therapy.(Up to 96 weeks after SYNCAR-001 infusion)
- Change over time in pulmonary function tests(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.(Up to 96 weeks after SYNCAR-001 infusion)