Open-label Study of ELA026 in Participants With Secondary Hemophagocytic Lymphohistiocytosis (sHLH)
Start Date
5/19/2022
Completion Date
6/1/2029
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 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.
Eligibility Criteria
Age Range: 6 years to No maximum
Interventions
ELA026
Conditions
Locations
University of Alabama at Birmingham School of Medicine
Birmingham, Alabama 35233
United States
Phoenix Children's Hospital
Phoenix, Arizona 85016
United States
University of California, Los Angeles
Los Angeles, California 90095
United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia 20007
United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida 33701
United States
Children's Healthcare of Atlanta - Center for Advanced Pediatrics
Atlanta, Georgia 30322
United States
Emory University
Atlanta, Georgia 30322
United States
National Institute of Allergy and Infectious Diseases (NIAID)
Rockville, Maryland 20892
United States
Columbia University
New York, New York 10032
United States
Cornell University
New York, New York 10065
United States
Hackensack University Medical Center
New York, New York 10065
United States
Memorial Sloan Kettering Cancer Center
New York, New York 10065
United States
Cleveland Clinic Main Campus
Cleveland, Ohio 44195
United States
Thomas Jefferson University
Philadelphia, Pennsylvania 19107
United States
Texas Children's Hospital
Houston, Texas 77030
United States
University of Texas MD Anderson Cancer Center
Houston, Texas 77030
United States
Huntsman Cancer Institute
Salt Lake City, Utah 84112
United States
Fred Hutchinson Cancer Center - Seattle Cancer Care Alliance (SCCA) Location
Seattle, Washington 98109
United States
Medizinische Universität Innsbruck
Innsbruck,
Austria
Medical University of Vienna
Vienna,
Austria
Universitätsklinikum Jena
Jena, Thuringia 07747
Germany
Schwarzwald-Baar Klinikum Villingen-Schwenningen
Villingen-Schwenningen, 78052
Germany
Azienda Ospedaliero Universitaria Meyer
Florence, 50139
Italy
IRCCS Istituto Giannina Gaslini
Genova, 16147
Italy
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Milan,
Italy
Fondazione IRCCS San Gerardo dei Tintori (Ospedale San Gerardo)
Monza, 20900
Italy
Azienda Ospedale Università di Padova
Padova, 35128
Italy
Bambino Gesu' Roma
Roma,
Italy
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Materno-Infantile Burlo Garofolo
Trieste, 34137
Italy
Amsterdam Universitair Medische Centra - Locatie Academisch Medisch Centrum
Amsterdam, Noord-Holland - NET 1105 AZ
Netherlands
Radboud Universitair Medisch Centrum
Nijmegen, 6525 GA
Netherlands
Erasmus UMC
Rotterdam,
Netherlands
Wilhelmina Kinderziekenhuis
Utrecht, 3584 EA
Netherlands
Clinica Universidad de Navarra - Madrid
Madrid, Madrid - SPA 28027
Spain
Clinica Universidad de Navarra - Pamplona
Pamplona, Navarre - SPA 31008
Spain
Hospital Universitario Virgen del Rocio
Seville, Sevilla - SPA 41013
Spain
Hospital Universitari i Politecnic La Fe
Valencia, Valencia - SPA 46026
Spain
Hospital 12 de Octubre, Madrid
Madrid,
Spain
Hospital Ramon y Cajal
Madrid,
Spain
Hospital La Fe Valencia
Valencia,
Spain
University College London Hospitals NHS Foundation Trust
London, England - UK NW1 2PG
United Kingdom