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NCT05416307PHASE2, PHASE3Recruiting

Open-label Study of ELA026 in Participants With Secondary Hemophagocytic Lymphohistiocytosis (sHLH)

Electra Therapeutics Inc.

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

Key Inclusion Criteria for Part 1: 1. ≥12 years at the time of HLH diagnosis (Cohort 1). 2. ≥6 years at the time of HLH diagnosis (Cohort 2-3). 3. Treatment naïve or relapsed/refractory (Cohorts 1 and 2). 4. Treatment naïve or early refractory (Cohort 3). 5. Participant with sHLH confirmed criteria based on fulfilling 5 out of 8 HLH-2004 diagnostic criteria. Key Inclusion Criteria for Part 2: 1. Cohort A: Adults with newly diagnosed, treatment-naïve, malignancy-associated sHLH. 2. Cohort B: Adults with newly diagnosed, treatment-naïve, non-malignancy-associated sHLH. 3. Cohort B: Adults with newly diagnosed, treatment-naïve, malignancy-associated sHLH, diagnosed by OHI index. 4. Cohort B: 13 to 17 years olds with newly diagnosed, treatment-naïve sHLH. 5. Cohort B: 6 to 12 year olds, with refractory sHLH (safety lead-in cohort). 6. Cohort B: 6 to 12 year olds, with newly diagnosed, treatment-naïve sHLH (after completion of safety lead-in cohort). Key Exclusion Criteria for Part 1: 1. Known or previous treatment for primary HLH 2. Any other significant concurrent, uncontrolled medical condition that in the opinion of the Investigator contraindicates participation in this study 3. Unknown trigger for sHLH 4. Active, relapsed/refractory malignancy for which no suitable therapies are available to treat the malignancy triggering the HLH 5. Allogeneic hemopoietic stem cell transplant (HSCT) within 100 days of the first dose of ELA026. 6. Ongoing administration of any therapies used to treat HLH (excluding dexamethasone) 7. 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: 1. Refractory sHLH (except for the safety lead-in cohort for 6-12 year olds in Cohort B). 2. Known or suspected primary or hereditary HLH. 3. Severe organ dysfunction. 4. Any other significant concurrent, uncontrolled medical condition that contraindicates participation in this study or prohibits completion of study procedures. 5. End-stage malignancy for which no suitable therapies are available to treat the malignancy triggering the HLH. 6. Allogeneic hemopoietic stem cell transplant within 100 days prior to the first dose of ELA026.

Interventions

DRUG

ELA026

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Conditions

Secondary Hemophagocytic Lymphohistiocytosis (sHLH)

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