A Post-authorization Study to Describe the Safety and Efficacy of Emapalumab for the Treatment of pHLH in Treatment Experienced Chinese Patients

Study Overview
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Brief Summary
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The goal of this post-authorization study is to describe safety and efficacy of emapalumab in treatment experienced Chinese patients with pHLH.

Detailed Description
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This is an open-label, multi center, single arm, post-authorization study aiming to describe safety and efficacy of emapalumab in treatment experienced Chinese patients with confirmed or suspected primary hemophagocytic lymphohistiocytosis (pHLH). The main objectives of the study are to collect safety and efficacy data on emapalumab in treatment experienced Chinese pHLH patients

Official Title
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An Open Label, Single Arm, Multi-Centre, Post-authorization Study to Describe the Safety and Efficacy of Emapalumab for the Treatment of Primary Hemophagocytic Lymphohistiocytosis in Treatment Experienced Chinese Patients

Conditions
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Primary Hemophagocytic Lymphohistiocytosis

Intervention / Treatment
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* Drug: Emapalumab-Lzsg 5 MG/ML [Gamifant]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female HLH patients of any age. Patients diagnosed with confirmed or suspected pHLH, based on; a molecular diagnosis or familial history consistent with pHLH or fulfilment of HLH-2004 diagnostic criteria, i.e., five out of eight of the criteria below: Fever Splenomegaly Cytopenias affecting 2 of 3 lineages in the peripheral blood (hemoglobin <90 g/L; platelets <100 x 109/L; neutrophils <1 x 109/L) Hypertriglyceridemia (fasting triglycerides ≥3 mmol/L or ≥265 mg/dL) and/or hypofibrinogenemia (≤1.5 g/L) Hemophagocytosis in bone marrow, spleen, or lymph nodes, with no evidence of malignancy. Low or absent NK-cell activity Ferritin ≥500 μg/L Soluble CD25 (sCD25; i.e., soluble IL-2 receptor) ≥2400 U/mL Presence of active HLH disease as assessed by the investigator. Patients must fulfil one of the following criteria as assessed by the investigator: Having not responded to previous conventional treatment of HLH Having not achieved a satisfactory response to previous conventional treatment of HLH or worsened Having reactivated HLH Showing intolerance to previous conventional treatment of HLH At the time of enrollment, eligible patients might still be receiving treatment (induction or maintenance) or might have already discontinued it. Expectation of survival beyond 1 week as judged by the investigator. Patient has expectation of proceeding to HSCT Informed consent signed by the patient (as required by local law), or by the patient's legally authorized representative(s) with the assent of patients who are legally capable of providing it, as applicable. Willing to use highly effective methods of contraception from study drug initiation to 6 months after the last dose of study drug, if female and of childbearing potential. Exclusion Criteria: Diagnosis of secondary HLH consequent to a proven rheumatic, metabolic or neoplastic disease. Active mycobacteria, Histoplasma capsulatum, Salmonella, or Leishmania infections. Evidence of latent tuberculosis. Presence of malignancy. Existence of any severe co-morbidity or any other medical condition which, in the opinion of the investigator, makes the patient unsuitable for the treatment History of hypersensitivity or allergy to any component of the study regimen (e.g., polysorbate). Receipt of a Bacillus Calmette-Guérin (BCG) vaccine within 12 weeks prior to Screening. Receipt of a live or attenuated live (other than BCG) vaccine within 4 weeks prior to Screening. Pregnant or lactating female patients. Enrollment in another concurrent clinical interventional study, or intake of an IMP, within three months prior to inclusion in this study Any condition or circumstance that in the opinion of the Investigator may make the patient unlikely to complete the study or comply with study procedures or requirements.
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
Interventional Model Description: This is an open-label, single-arm, multi-centre study to collect safety and efficacy data on emapalumab in treatment experienced male and female patients diagnosed with pHLH. The study will be performed in China.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: emapalumab<br>emapalumab solution for infusion twice weekly at a starting dose of 1 mg/kg | Drug: Emapalumab-Lzsg 5 MG/ML [Gamifant]<br>* iv<br>* Other names: Gamifant;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Permanent discontinuation of study drug due to emapalumab-related adverse event | as judged by Investigator | until conditioning for hematopoietic stem cell transplant (HSCT), likely within 6 months from first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response | measured as complete response, partial response, or HLH improvement | end of treatment or week 8 (whichever occurs earlier) | 
| Time to first overall response | from first dose of study drug to first response | end of treatment, likely within 6 months from first dose | 
| Cumulative duration of response | total time in response | end of treatment, likely within 6 months from first dose | 
| Ability to reduce glucocorticoids by 50% or more | reduction from baseline dose during emapalumab treatment | end of treatment, likely within 6 months from first dose | 
| Investigator assessed response | Investigator's assessment of how patient responds to treatment and rated as complete response, partial response, or no response | end of treatment or week 8 (whichever occurs earlier) | 
| Survival | To start of HSCT conditioning and after time from HSCT to death | end of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pHLH