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

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.

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.