Evaluation of the Safety and Efficacy of ELA026 in Participants With Secondary Hemophagocytic Lymphohistiocytosis

Study Overview
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Brief Summary
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Hemophagocytic lymphohistiocytosis is a rare, aggressive and life-threatening syndrome of excessive immune activation. ELA026 is a fully human IgG1 SIRP-directed monoclonal antibody designed to reduce 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 secondary hemophagocytic lymphohistiocytosis.

Detailed Description
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This study is an open-label, single arm, multicenter interventional study, comprised of 4 cohorts; a dose escalating cohort (cohort 1) followed by 3 fixed dose cohorts (Cohorts 2-4). Newly diagnosed and previously treated participants with secondary hemophagocytic lymphohistiocytosis will be enrolled and treated over 12-weeks. Secondary hemophagocytic lymphohistiocytosis is the most common form of this disease and is typically associated with several other clinical conditions (eg, malignancy associated HLH (m-HLH), infection, or autoimmune disease).

Official Title
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A Phase 1b, Open-label, Single-arm, Multicenter Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of Multiple Doses of ELA026 in Participants With Secondary Hemophagocytic Lymphohistiocytosis (sHLH)

Conditions
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Secondary Hemophagocytic Lymphohistiocytosis (sHLH)

Intervention / Treatment
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* Drug: ELA026


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: All countries: ≥12 years at the time of HLH diagnosis (Cohort 1-4). US only: ≥12 years at the time of HLH diagnosis (Cohort 1-4) and 6 to <12 years at the time of HLH diagnosis (Cohorts 2-4) Treatment naïve OR; Relapsed refractory HLH. Participant is hospitalized with HLH confirmed criteria based on fulﬁlling 5 out of 8 HLH-2004 diagnostic criteria Key Exclusion Criteria: 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 Hemopoietic Stem Cell Transplant (HSCT) within 100 days of the ﬁrst dose of ELA026. All countries except US: Treatment with CAR T-Cell therapy within 3 months of the ﬁrst dose of ELA026. US Only: Treatment with CAR T-Cell therapy allowed within 3 months of first dose. Ongoing administration of any investigational treatment (excluding dexamethasone) within 14 days prior to Screening or 5 drug half-lives, whichever is shorter Live or attenuated vaccine received within 6 weeks or bacille Calmette-Guerin (BCG) vaccine within 12 weeks prior to Screening

Ages Eligible for Study
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Minimum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ELA026<br>Cohort 1: Single dose escalation up to 3.0 mg/kg IV or SC Cohorts 2-4: dose, route, and frequency of administration (IV or SC) to be determined | Drug: ELA026<br>* Single or multiple daily doses of ELA026<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events [Safety and tolerability] | Incidence of adverse events (AEs) including dose-limiting toxicities (DLTs), serious adverse events (SAEs), deaths, AEs leading to withdrawal from study | By week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Response to Treatment | Achievement of a complete response (CR), modified complete response (mCR), partial response (PR) or HLH improvement | By week 4 | 
| Plasma concentrations of ELA026 |  | Baseline to week 12 | 
| Change from baseline in monocyte levels |  | Baseline to week 12 | 
| Incidence of Anti-drug antibodies to ELA026 |  | Baseline to week 12 |