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

Official title

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

Overview

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.

Interventions

• Drug ELA026
  Multiple doses of ELA026

Primary outcome measures

• Part 1: Number of Participant with Incidence of Treatment-Emergent Adverse Events (TEAEs) [Safety and tolerability] [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]

Secondary outcome measures (3)

• 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) [Time frame: Up to Day 29]
• Number of Participants with TEAEs [Time frame: Up to Week 12]

Eligibility criteria

Key Inclusion Criteria for Part 1:

• ≥12 years at the time of HLH diagnosis (Cohort 1).
• ≥6 years at the time of HLH diagnosis (Cohort 2-3).
• Treatment naïve or relapsed/refractory (Cohorts 1 and 2).
• Treatment naïve or early refractory (Cohort 3).
• Participant with sHLH confirmed criteria based on fulfilling 5 out of 8 HLH-2004 diagnostic criteria.

Key Inclusion Criteria for Part 2:

• Cohort A: Adults with newly diagnosed, treatment-naïve, malignancy-associated sHLH.
• Cohort B: Adults with newly diagnosed, treatment-naïve, non-malignancy-associated sHLH.
• Cohort B: Adults with newly diagnosed, treatment-naïve, malignancy-associated sHLH, diagnosed by OHI index.
• Cohort B: 13 to 17 years olds with newly diagnosed, treatment-naïve sHLH.
• Cohort B: 6 to 12 year olds, with refractory sHLH (safety lead-in cohort).
• 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:

• Known or previous treatment for primary HLH
• Any other significant concurrent, uncontrolled medical condition that in the opinion of the Investigator contraindicates participation in this study
• Unknown trigger for sHLH
• Active, relapsed/refractory malignancy for which no suitable therapies are available to treat the malignancy triggering the HLH
• Allogeneic hemopoietic stem cell transplant (HSCT) within 100 days of the first dose of ELA026.
• Ongoing administration of any therapies used to treat HLH (excluding dexamethasone)
• 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:

• Refractory sHLH (except for the safety lead-in cohort for 6-12 year olds in Cohort B).
• Known or suspected primary or hereditary HLH.
• Severe organ dysfunction.
• Any other significant concurrent, uncontrolled medical condition that contraindicates participation in this study or prohibits completion of study procedures.
• End-stage malignancy for which no suitable therapies are available to treat the malignancy triggering the HLH.
• Allogeneic hemopoietic stem cell transplant within 100 days prior to the first dose of ELA026.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 18 centers

• University of Alabama at Birmingham School of Medicine — Birmingham
• Phoenix Children's Hospital — Phoenix
• University of California, Los Angeles — Los Angeles
• MedStar Georgetown University Hospital — Washington D.C.
• Johns Hopkins All Children's Hospital — St. Petersburg
• Children's Healthcare of Atlanta - Center for Advanced Pediatrics — Atlanta
• Emory University — Atlanta
• National Institute of Allergy and Infectious Diseases (NIAID) — Rockville
• … and 10 more centers

Italy · 7 centers

• Azienda Ospedaliero Universitaria Meyer — Florence
• IRCCS Istituto Giannina Gaslini — Genova
• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico — Milan
• Fondazione IRCCS San Gerardo dei Tintori (Ospedale San Gerardo) — Monza
• Azienda Ospedale Università di Padova — Padova
• Bambino Gesu' Roma — Roma
• Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Materno-Infantile Burlo Garo — Trieste

Spain · 7 centers

• Clinica Universidad de Navarra - Madrid — Madrid
• Clinica Universidad de Navarra - Pamplona — Pamplona
• Hospital Universitario Virgen del Rocio — Seville
• Hospital Universitari i Politecnic La Fe — Valencia
• Hospital 12 de Octubre, Madrid — Madrid
• Hospital Ramon y Cajal — Madrid
• Hospital La Fe Valencia — Valencia

Netherlands · 4 centers

• Amsterdam Universitair Medische Centra - Locatie Academisch Medisch Centrum — Amsterdam
• Radboud Universitair Medisch Centrum — Nijmegen
• Erasmus UMC — Rotterdam
• Wilhelmina Kinderziekenhuis — Utrecht

Austria · 2 centers

• Medizinische Universität Innsbruck — Innsbruck
• Medical University of Vienna — Vienna

Germany · 2 centers

• Universitätsklinikum Jena — Jena
• Schwarzwald-Baar Klinikum Villingen-Schwenningen — Villingen-Schwenningen

United Kingdom · 1 center

• University College London Hospitals NHS Foundation Trust — London

Identifiers

NCT: NCT05416307 · ELA026-CP002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗