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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
156
Multiple doses of ELA026
University of Alabama at Birmingham School of Medicine
Birmingham, Alabama, United States
RECRUITINGPhoenix Children's Hospital
Phoenix, Arizona, United States
ACTIVE_NOT_RECRUITINGUniversity of California, Los Angeles
Los Angeles, California, United States
ACTIVE_NOT_RECRUITINGMedStar Georgetown University Hospital
Washington D.C., District of Columbia, United States
Part 1: Number of Participant with Incidence of Treatment-Emergent Adverse Events (TEAEs) [Safety and tolerability]
Incidence of adverse events (AEs) including dose-limiting toxicities (DLTs), serious adverse events (SAEs), deaths, AEs leading to withdrawal from study
Time frame: Up to Week 12
Part 2 (Cohort A): 56-day Survival Rate in Participants with mHLH and Have Lymphoma as the Cancer Trigger
Time frame: 56 days
Number of Participants Achieving Early Survival (Cohort A)
Time frame: up to 90 days
Number of Participants Achieving HLH Disease Response by Day 29 (Cohort A)
HLH disease response includes achievement of CR, mCR, PR, or HI.
Time frame: Up to Day 29
Number of Participants with TEAEs
Time frame: Up to Week 12
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Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States
RECRUITINGChildren's Healthcare of Atlanta - Center for Advanced Pediatrics
Atlanta, Georgia, United States
RECRUITINGEmory University
Atlanta, Georgia, United States
RECRUITINGColumbia University
New York, New York, United States
RECRUITINGCornell University
New York, New York, United States
RECRUITINGMemorial Sloan Kettering Cancer Center
New York, New York, United States
RECRUITING...and 24 more locations