Open-label Study of ELA026 in Participants with Secondary Hemophagocytic Lymphohistiocytosis (sHLH)
- Conditions
- Secondary Hemophagocytic Lymphohistiocytosis (sHLH)
- Interventions
- Registration Number
- NCT05416307
- Lead Sponsor
- Electra Therapeutics Inc.
- Brief Summary
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.
- Detailed Description
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 TN adult and pediatric sHLH participants. All participants are diagnosed with HLH-2004 criteria unless indicated. Cohort A (primary cohort) will enroll 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 TN mHLH diagnosed by biomarker criteria but not meeting HLH-2004 diagnostic criteria; and 6 to 17 year old participants with 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 156
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1 ELA026 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. Part 2 ELA026 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.
- Primary Outcome Measures
Name Time Method Part 1: Number of Participant with Incidence of Treatment-Emergent Adverse Events (TEAEs) [Safety and tolerability] 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 56 days
- Secondary Outcome Measures
Name Time Method 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 HLH disease response includes achievement of CR, mCR, PR, or HI.
Number of Participants with TEAEs Up to Week 12
Trial Locations
- Locations (13)
University of Alabama
🇺🇸Birmingham, Alabama, United States
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
University of California, Los Angeles
🇺🇸Los Angeles, California, United States
MedStar Georgetown
🇺🇸Washington, District of Columbia, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
MD Anderson
🇺🇸Houston, Texas, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Medical University of Vienna
🇦🇹Vienna, Austria
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
🇮🇹Milan, Italy
Amsterdam UMC
🇳🇱Amsterdam, Netherlands
Erasmus UMC
🇳🇱Rotterdam, Netherlands
Hospital Ramon y Cajal
🇪🇸Madrid, Spain
University College London Hospitals
🇬🇧London, United Kingdom