A Multipart, Open-label, Single-arm, Multicenter Study to Evaluate the Safety, Efficacy and Pharmacokinetics of ELA026 in Participants With Secondary Hemophagocytic Lymphohistiocytosis (sHLH)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 156
- 试验地点
- 56
- 主要终点
- Part 1: Number of Participant with Incidence of Treatment-Emergent Adverse Events (TEAEs) [Safety and tolerability]
研究概览
简要总结
Hemophagocytic lymphohistiocytosis is a rare, aggressive and life-threatening syndrome of excessive immune activation. Secondary hemophagocytic lymphohistiocytosis (sHLH) is the most common form of this disease and is typically associated with several other clinical conditions (eg, malignancy associated HLH (mHLH), infection, or autoimmune disease). ELA026 is a fully human immunoglobulin G1 (IgG1) signal regulatory protein (SIRP)-directed monoclonal antibody designed to deplete the myeloid and T cells driving the inflammation. The purpose of this study is to assess the safety, efficacy pharmacokinetics and pharmacodynamics of ELA026 in participants with sHLH.
详细描述
This study consists of two parts: Phase 1b (Part 1) and Phase 2/3 (Part 2).
Part 1 is designed to evaluate the safety, efficacy, pharmacodynamics, and pharmacokinetics of ELA026 in pediatric and adult participants with treatment-naïve (TN) and relapsed/refractory sHLH. The main objectives of Part 1 are to determine the safety of ELA026 administered intravenously (IV) and subcutaneously (SC) to participants with sHLH and to identify the recommended Phase 3 dose and schedule for ELA026. Participants will be enrolled into a dose-escalating cohort (Cohort 1) followed by two fixed dose cohorts (Cohorts 2-3) treated over 12-weeks.
Part 2 (SURPASS) is designed as an open-label, single-arm, multicenter, historical control registrational study to evaluate ELA026 in newly diagnosed TN adult and pediatric sHLH participants. All participants are diagnosed with HLH-2004 criteria unless indicated. Cohort A (primary cohort) will enroll newly diagnosed TN participants ≥18 years old with mHLH. Cohort B (exploratory cohort) will enroll participants including ≥18 years old participants with TN sHLH not triggered by malignancy; ≥18 years old participants with newly diagnosed TN mHLH diagnosed by biomarker criteria but not meeting HLH-2004 diagnostic criteria; and 6 to 17 year old participants with newly diagnosed TN sHLH (due to any trigger). For 6 to 12 year old participants, there is a safety lead-in cohort with refractory sHLH.
Part 1 is closed to recruitment and Part 2 is recruiting for eligible participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •for Part 1:
- •≥12 years at the time of HLH diagnosis (Cohort 1).
- •≥6 years at the time of HLH diagnosis (Cohort 2-3).
- •Treatment naïve or relapsed/refractory (Cohorts 1 and 2).
- •Treatment naïve or early refractory (Cohort 3).
- •Participant with sHLH confirmed criteria based on fulfilling 5 out of 8 HLH-2004 diagnostic criteria.
- •Key Inclusion Criteria for Part 2:
- •Cohort A: Adults with newly diagnosed, treatment-naïve, malignancy-associated sHLH.
- •Cohort B: Adults with newly diagnosed, treatment-naïve, non-malignancy-associated sHLH.
- •Cohort B: Adults with newly diagnosed, treatment-naïve, malignancy-associated sHLH, diagnosed by OHI index.
- •Cohort B: 13 to 17 years olds with newly diagnosed, treatment-naïve sHLH.
- •Cohort B: 6 to 12 year olds, with refractory sHLH (safety lead-in cohort).
- •Cohort B: 6 to 12 year olds, with newly diagnosed, treatment-naïve sHLH (after completion of safety lead-in cohort).
排除标准
- •for Part 1:
- •Known or previous treatment for primary HLH
- •Any other significant concurrent, uncontrolled medical condition that in the opinion of the Investigator contraindicates participation in this study
- •Unknown trigger for sHLH
- •Active, relapsed/refractory malignancy for which no suitable therapies are available to treat the malignancy triggering the HLH
- •Allogeneic hemopoietic stem cell transplant (HSCT) within 100 days of the first dose of ELA
- •Ongoing administration of any therapies used to treat HLH (excluding dexamethasone)
- •Live or attenuated vaccine received within 6 weeks or bacille Calmette-Guerin (BCG) vaccine within 12 weeks prior to Screening
- •Key Exclusion Criteria for Part 2:
- •Refractory sHLH (except for the safety lead-in cohort for 6-12 year olds in Cohort B).
- •Known or suspected primary or hereditary HLH.
- •Severe organ dysfunction.
- •Any other significant concurrent, uncontrolled medical condition that contraindicates participation in this study or prohibits completion of study procedures.
- •End-stage malignancy for which no suitable therapies are available to treat the malignancy triggering the HLH.
- •Allogeneic hemopoietic stem cell transplant within 100 days prior to the first dose of ELA026.
研究组 & 干预措施
Part 2 ELA026
Cohort A and Cohort B: priming dose: 0.1 mg/kg IV on Day 1; loading dose 0.3 mg/kg IV on Days 2- 4, followed by twice weekly maintenance doses of 0.5 mg/kg (IV/SC) from Day 8 to Day 81.
干预措施: ELA026 (Drug)
Part 1 ELA026
Cohort 1: Single dose escalation up to 3.0 mg/kg IV or SC.
Cohort 2: priming dose: 0.1 mg/kg IV on Day 1; 0.3 mg/kg IV on Day 2 - 4, followed by weekly maintenance doses of 1 mg/kg IV/SC from Day 8 to Day 81.
Cohort 3: priming dose: 0.1 mg/kg IV on Day 1; 0.3 mg/kg IV on Days 2 - 4, followed by twice weekly maintenance doses of 0.5 mg/kg IV/SC from Day 8 to Day 81.
干预措施: ELA026 (Drug)
结局指标
主要结局
Part 1: Number of Participant with Incidence of Treatment-Emergent Adverse Events (TEAEs) [Safety and tolerability]
时间窗: Up to Week 12
Incidence of adverse events (AEs) including dose-limiting toxicities (DLTs), serious adverse events (SAEs), deaths, AEs leading to withdrawal from study
Part 2 (Cohort A): 56-day Survival Rate in Participants with mHLH and Have Lymphoma as the Cancer Trigger
时间窗: 56 days
次要结局
- Number of Participants Achieving Early Survival (Cohort A)(up to 90 days)
- Number of Participants Achieving HLH Disease Response by Day 29 (Cohort A)(Up to Day 29)
- Number of Participants with TEAEs(Up to Week 12)