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

A Multipart, Open-label, Single-arm, Multicenter Study to Evaluate the Safety, Efficacy and Pharmacokinetics of ELA026 in Participants With Secondary Hemophagocytic Lymphohistiocytosis (sHLH)

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.

Study Overview

• Status: Recruiting
• Conditions: Secondary Hemophagocytic Lymphohistiocytosis (sHLH)
• Intervention / Treatment: Drug: ELA026

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.

• Study Type: Interventional
• Enrollment (Estimated): 156
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials; Phone Number: Please email; Email: clinicaltrials@electra-therapeutics.com

Study Locations

• Austria
  • Innsbruck, Austria
    • Withdrawn
    • Medizinische Universität Innsbruck
  • Vienna, Austria
    • Completed
    • Medical University of Vienna
• Germany
  • Villingen-Schwenningen, Germany, 78052
    • Recruiting
    • Schwarzwald-Baar Klinikum Villingen-Schwenningen
  • Thuringia
    • Jena, Thuringia, Germany, 07747
      • Recruiting
      • Universitätsklinikum Jena
• Italy
  • Florence, Italy, 50139
    • Recruiting
    • Azienda Ospedaliero Universitaria Meyer
  • Genova, Italy, 16147
    • Recruiting
    • IRCCS Istituto Giannina Gaslini
  • Milan, Italy
    • Completed
    • Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
  • Monza, Italy, 20900
    • Recruiting
    • Fondazione IRCCS San Gerardo dei Tintori (Ospedale San Gerardo)
  • Padova, Italy, 35128
    • Recruiting
    • Azienda Ospedale Università di Padova
  • Roma, Italy
    • Withdrawn
    • Bambino Gesu' Roma
  • Trieste, Italy, 34137
    • Recruiting
    • Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Materno-Infantile Burlo Garofolo
• Netherlands
  • Nijmegen, Netherlands, 6525 GA
    • Recruiting
    • Radboud Universitair Medisch Centrum
  • Rotterdam, Netherlands
    • Active, not recruiting
    • Erasmus UMC
  • Utrecht, Netherlands, 3584 EA
    • Recruiting
    • Wilhelmina Kinderziekenhuis
  • Noord-Holland - NET
    • Amsterdam, Noord-Holland - NET, Netherlands, 1105 AZ
      • Recruiting
      • Amsterdam Universitair Medische Centra - Locatie Academisch Medisch Centrum
• Spain
  • Madrid, Spain
    • Withdrawn
    • Hospital 12 de Octubre, Madrid
  • Madrid, Spain
    • Completed
    • Hospital Ramon y Cajal
  • Valencia, Spain
    • Withdrawn
    • Hospital La Fe Valencia
  • Madrid - SPA
    • Madrid, Madrid - SPA, Spain, 28027
      • Recruiting
      • Clínica Universidad de Navarra - Madrid
  • Navarre - SPA
    • Pamplona, Navarre - SPA, Spain, 31008
      • Recruiting
      • Clinica Universidad de Navarra - Pamplona
  • Sevilla - SPA
    • Seville, Sevilla - SPA, Spain, 41013
      • Recruiting
      • Hospital Universitario Virgen del Rocio
  • Valencia - SPA
    • Valencia, Valencia - SPA, Spain, 46026
      • Recruiting
      • Hospital Universitari i Politecnic La Fe
• United Kingdom
  • England - UK
    • London, England - UK, United Kingdom, NW1 2PG
      • Recruiting
      • University College London Hospitals NHS Foundation Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • University of Alabama at Birmingham School of Medicine
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Active, not recruiting
      • Phoenix Children's Hospital
  • California
    • Los Angeles, California, United States, 90095
      • Active, not recruiting
      • University of California, Los Angeles
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Recruiting
      • MedStar Georgetown University Hospital
  • Florida
    • St. Petersburg, Florida, United States, 33701
      • Recruiting
      • Johns Hopkins All Children's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Children's Healthcare of Atlanta - Center for Advanced Pediatrics
  • Maryland
    • Rockville, Maryland, United States, 20892
      • Recruiting
      • National Institute of Allergy and Infectious Diseases (NIAID)
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University
    • New York, New York, United States, 10065
      • Recruiting
      • Cornell University
    • New York, New York, United States, 10065
      • Recruiting
      • Hackensack University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic Main Campus
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Texas Children's Hospital
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • Huntsman Cancer Institute
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutchinson Cancer Center - Seattle Cancer Care Alliance (SCCA) Location

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: ELA026; Multiple doses of ELA026
Experimental: 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.	Drug: ELA026; Multiple doses of ELA026

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Up to Week 12
Part 2 (Cohort A): 56-day Survival Rate in Participants with mHLH and Have Lymphoma as the Cancer Trigger		56 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Achieving Early Survival (Cohort A)		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.	Up to Day 29
Number of Participants with TEAEs		Up to Week 12

Collaborators and Investigators

• Sponsor: Electra Therapeutics Inc.
• Investigators: Study Director: Medical Director, Electra Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2022
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: June 6, 2022
• First Submitted That Met QC Criteria: June 8, 2022
• First Posted (Actual): June 13, 2022

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Lymphatic Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Neoplasm Metastasis; Lymphohistiocytosis, Hemophagocytic
• Other Study ID Numbers: ELA026-CP002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No