NCT07053800招募中2 期
A Single-Arm, Open-Label, Phase II Study to Determine the Safety and Efficacy of Obecabtagene Autoleucel (Obe-cel) in Participants With Severe, Refractory Systemic Lupus Erythematosus With Active Lupus Nephritis
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 35
- 试验地点
- 15
- 主要终点
- Proportion of participants who achieve complete renal response (CRR) at 6 months post-obe-cel infusion without rescue medications, among all participants who received obe-cel infusion
研究概览
简要总结
The purpose of this trial is to evaluate the efficacy and safety of obecabtagene autoleucel (obe-cel) administered once following lymphodepletion in participants with severe, refractory systemic lupus erythematosus (SLE) and active lupus nephritis (LN).
详细描述
This is a Phase 2 study to determine the efficacy and safety of obe-cel in participants with severe, refractory SLE with active LN.
The study comprises 3 periods:
- Screening Period: From Day -30 (+7) to Day of Enrollment
- Treatment Period: From Day -8 to Day 1 - Participants will be evaluated to confirm eligibility for lymphodepletion, and thereafter receive lymphodepletion.
Obe-cel Administration: If the participant's eligibility for receiving obe-cel infusion is confirmed, the participant is to receive a single obe-cel infusion on Day 1. 3. Post-treatment Period: From Day 1 to End of Study all participants will be followed up for efficacy and safety evaluation.
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
- 12 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing and able to give written informed consent for participation in the study or written informed consent signed by a legal guardian or representative
- •Ability and willingness to adhere to protocol's Schedule of Activities and other requirements
- •Participants must be 12 to 65 years of age inclusive at the time of signing the informed consent.
- •Female Participants: - a female participant is eligible to participate if she is not pregnant or breastfeeding
- •Diagnosis of SLE fulfilling the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) Classification Criteria for Systemic Lupus Erythematosus.
- •Positive for at least 1 of the following autoantibodies: antinuclear antibodies (ANA), or anti-dsDNA or anti-Smith.
- •Severe, Active SLE defined as:
- •SLEDAI-2K score of ≥ 8 points AND
- •Severe active LN based on a renal biopsy: Class III, IV or V (V only in combination with class III or IV)
- •Refractory SLE defined as failure to previous lines of therapy
排除标准
- •Prior treatment at any time with anti-CD19 therapy
- •More than 1 acute, severe lupus-related flare during screening that needs immediate treatment and/or makes the immunosuppressive washout impossible
- •Significant, likely irreversible organ damage related to SLE (e.g., end-stage renal disease) that in the opinion of the Investigator renders CD19 CAR T cell therapy unlikely to benefit the participant
- •History of primary antiphospholipid antibody syndrome
- •Active or uncontrolled fungal, bacterial, or viral infection
- •History of malignant neoplasms unless disease free for at least 24 months
- •History of heart, lung, renal, liver transplant or hematopoietic stem cell transplant
研究组 & 干预措施
Obe-cel
Experimental
干预措施: Obecabtagene autoleucel (Biological)
结局指标
主要结局
Proportion of participants who achieve complete renal response (CRR) at 6 months post-obe-cel infusion without rescue medications, among all participants who received obe-cel infusion
时间窗: Month 6
CRR is defined as change in * urine protein creatinine ratio (UPCR) and * estimated glomerular filtration rate (eGFR) and * without use of rescue medication
次要结局
- Proportion of participants with CRR.(Up to Month 24)
- Duration of CRR.(Up to Month 24)
- Proportion of participants with Partial Renal Response (PRR)(Up to Month 24)
- To evaluate safety of obe-cel(Up to Month 24)
- Time to CRR(Up to Month 24)
- Proportion of participants who achieve response according to Definition of Remission in SLE (DORIS) at 6 months post-obe-cel infusion, among all patients who received obe-cel infusion(Month 6)
- Proportion of participants with CRR.(Up to Month 24)
- Duration of CRR.(Up to Month 24)
- Proportion of participants with Partial Renal Response (PRR)(Up to Month 24)
- Remission over time as specified by DORIS.(Up to Month 24)
- Time to response, as specified by DORIS.(Up to Month 24)
- Remission over time, as specified by the definition of remission in Lupus Low Disease Activity State (LLDAS).(Up to Month 24)
- Changes from baseline in EuroQoL (EQ)-5 Dimension (D).(Up to Month 24)
- Time to remission and duration of remission, as specified by the definition of remission in LLDAS.(Up to Month 24)
- Time from obe-cel infusion to first disease flare according to definition of flare in Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI-2K Flare Index (SFI)(Up to Month 24)
- Changes from baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue(Up to Month 24)
- Changes from baseline in Disability Health Assessment Questionnaire - Disability Index (HAQ-DI).(Up to Month 24)
- Changes from baseline in Short Form Health Survey (SF-36).(Up to Month 24)
- To evaluate safety of obe-cel(Up to Month 24)
- Pharmacokinetics (PK) of CAR-T cells post obe-cel infusion - Maximum concentration (Cmax)(Up to Month 24)
- Pharmacokinetics (PK) of CAR-T cells post obe-cel infusion - time to maximum concentration (Tmax)(Up to Month 24)
- Pharmacokinetics (PK) of CAR-T cells post obe-cel infusion - last observed quantifiable concentration (Clast)(Up to Month 24)
- Pharmacokinetics (PK) of CAR-T cells post obe-cel infusion - time to last observed quantifiable concentration (Tlast)(Up to Month 24)
- Pharmacokinetics (PK) of CAR-T cells post obe-cel infusion - area under the curve (AUC)(Up to Month 24)
- To evaluate pharmacodynamics (PD) of obe-cel(Up to Month 24)
研究者
研究点 (15)
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