Clinical trial NCT05416307: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Secondary Hemophagocytic Lymphohistiocytosis (sHLH)
Lead sponsor: Electra Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2022-06-13
Enrollment: 156
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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 TN adult and pediatric sHLH participants. All participants are diagnosed with HLH-2004 criteria unless indicated. Cohort A (primary cohort) will enroll 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 TN mHLH diagnosed by biomarker criteria but not meeting HLH-2004 diagnostic criteria; and 6 to 17 year old participants with 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: 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. ≥18 years old, with treatment-naïve mHLH, diagnosed by HLH-2004 criteria, triggered by any type of malignancy (Cohort A).
2. ≥18 years old ≥12 to 17 years old with treatment-naïve sHLH, diagnosed by HLH-2004 criteria, not triggered by any type of malignancy (Cohort B).
3. ≥18 years old, with treatment-naïve mHLH, diagnosed by biomarker criteria but not meeting HLH-2004 criteria, triggered by any type of malignancy (Cohort B).
4. 13 to 17 years old with treatment-naïve sHLH, diagnosed by HLH-2004 criteria, due to any trigger (Cohort B).
5. 6 to 12 year old, with refractory sHLH, diagnosed by HLH-2004 criteria due to any trigger (refractory defined as ≤ 2 weeks of HLH-directed therapy with suboptimal response as determined by the investigator - safety lead-in cohort).
6. 6 to 12 year old treatment-naïve sHLH diagnosed by HLH-2004 criteria due to any trigger.

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 old 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 or within 30 days of study enrollment.

Primary outcomes:
measure: Part 1: Number of Participant with Incidence of Treatment-Emergent Adverse Events (TEAEs) [Safety and tolerability]
timeFrame: Up to Week 12
measure: Part 2 (Cohort A): 56-day Survival Rate in Participants with mHLH and Have Lymphoma as the Cancer Trigger
timeFrame: 56 days
Secondary outcomes:
measure: Number of Participants Achieving Early Survival (Cohort A)
timeFrame: up to 90 days
measure: Number of Participants Achieving HLH Disease Response by Day 29 (Cohort A)
timeFrame: Up to Day 29
measure: Number of Participants with TEAEs
timeFrame: Up to Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Washington
country: United States
facility: MedStar Georgetown
state: District of Columbia
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Milan
country: Italy
facility: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
city: Rotterdam
country: Netherlands
facility: Erasmus UMC
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: London
country: United Kingdom
facility: University College London Hospitals
Study officials:
affiliation: Electra Therapeutics Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: