A study conducted in several Countries, to give access to emapalumab, and to study how efficacious and safe is in children with primary Hemophagocytic Lymphohistiocytosis (pHLH)

An Open-label, Single Arm, Multicenter Study to Broaden Access to Emapalumab, an Anti-Interferon Gamma (Anti-IFN?) Monoclonal Antibody, and to Assess its Efficacy, Safety, Impact on Quality of Life, and Long-term Outcome in Pediatric Patients with Primary Hemophagocytic Lymphohistiocytosis

Status

Not yet recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2017-003114-10-DE

Enrollment

Registered

2018-02-06

Start date

2018-09-06

Completion date

Unknown

Last updated

2022-05-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Primary Hemophagocytic Lymphohistiocytosis (pHLH) MedDRA version: 21.1 Level: PT Classification code 10071583 Term: Haemophagocytic lymphohistiocytosis System Organ Class: 10021428 - Immune system disorders

Interventions

Product Name: Emapalumab Product Code: NI-0501 Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: EMAPALUMAB Current Sponsor code: NI-0501 Other descriptive name: Fully hu

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Of note, the enrolment of patients will continue until emapalumab is commercially available for a given indication, until sample size is reached; thus, US enrolment will be limited to treatment-naïve patients. Male and female pHLH patients, from birth up to and including 18 years at diagnosis of HLH. 2. A molecular diagnosis or familial history consistent with pHLH or fulfilment of HLH-2004 diagnostic criteria, i.e., five of the eight criteria below: - Fever - Splenomegaly - Cytopenias affecting 2 of 3 lineages in the peripheral blood (hemoglobin =65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: 1. Diagnosis of secondary HLH consequent to a proven rheumatic, metabolic or neoplastic disease. 2. Active mycobacteria, Histoplasma Capsulatum, Shigella, Salmonella, Campylobacter or Leishmania infections. 3. Evidence of latent tuberculosis. 4. Presence of malignancy. 5. Patients who have another concomitant disease or malformation severely affecting cardiovascular, pulmonary, central nervous system (CNS), liver, or renal function that in the opinion of the Investigator may significantly affect the likelihood to respond to treatment and/or the assessment of emapalumab safety and/or efficacy. 6. History of hypersensitivity or allergy to any component of the study regimen (e.g., polysorbate). 7. Receipt of a bacille Calmette-Guerin (BCG) vaccine within 12 weeks prior to Screening. 8. Receipt of a live or attenuated live (other than BCG) vaccine within 6 weeks prior to Screening. 9. Pregnant or lactating female patients.

Design outcomes

Primary

Measure	Time frame
Main Objective: • To gather additional safety and efficacy data on emapalumab in pHLH patients. ;Secondary Objective: • To assess a starting dose of emapalumab of 3 mg/kg. • To assess the impact of emapalumab on Quality of Life (QOL). • To gather additional evidence on the long-term outcome of pHLH patients treated with emapalumab. • To further evaluate the pharmacokinetic (PK) profile of emapalumab in pHLH patients. • To further evaluate the pharmacodynamic (PD) effects (levels of circulating Total Interferon Gamma (IFN?) and biomarkers of its neutralization, namely CXCL9 and CXCL10). • To assess the profile of other relevant HLH biomarkers, e.g., sCD25 and other exploratory biomarkers. •To monitor for potential occurrence of anti-drug antibodies (ADAs).;Primary end point(s): Primary efficacy endpoint: • Overall Response, i.e., achievement of either Complete or Partial Response or HLH Improvement, at End of Treatment (EOT) or Week 8 (whichever occurs earlier). ;Timepoint(s) of evaluation of this end point: See E.5.1	—

Measure

Time frame

Main Objective: • To gather additional safety and efficacy data on emapalumab in pHLH patients. ;Secondary Objective: • To assess a starting dose of emapalumab of 3 mg/kg. • To assess the impact of emapalumab on Quality of Life (QOL). • To gather additional evidence on the long-term outcome of pHLH patients treated with emapalumab. • To further evaluate the pharmacokinetic (PK) profile of emapalumab in pHLH patients. • To further evaluate the pharmacodynamic (PD) effects (levels of circulating Total Interferon Gamma (IFN?) and biomarkers of its neutralization, namely CXCL9 and CXCL10). • To assess the profile of other relevant HLH biomarkers, e.g., sCD25 and other exploratory biomarkers. •To monitor for potential occurrence of anti-drug antibodies (ADAs).;Primary end point(s): Primary efficacy endpoint: • Overall Response, i.e., achievement of either Complete or Partial Response or HLH Improvement, at End of Treatment (EOT) or Week 8 (whichever occurs earlier). ;Timepoint(s) of evaluation of this end point: See E.5.1

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Secondary

Measure	Time frame
Secondary end point(s): Secondary efficacy endpoints: • Overall Survival, including survival to HSCT and survival after either HSCT or last emapalumab infusion (if HSCT is not performed) • Event-free Survival • Overall Response, i.e., achievement of either Complete or Partial Response or HLH Improvement, at start of conditioning (or at last emapalumab infusion if HSCT is not performed) • Duration of Response, ie, maintenance of response achieved any time during the study (with censoring time at start of conditioning for patients with no events) • Time to Response at any time during the study • Number of patients able to reduce glucocorticoids by 50% or more of baseline dose during emapalumab treatment • Number of patients able to proceed to HSCT, when deemed indicated • QOL indices. Safety endpoints: • Incidence, severity, causality and outcomes of AEs (serious and non-serious). • Evolutions of relevant laboratory parameters, e.g., complete blood cell (CBC) count, liver and renal function tests, and coagulation parameters. • Number of patients who discontinued emapalumab treatment for safety reasons. PK/PD Endpoints: • Serum concentrations of emapalumab to further evaluate emapalumab PK profile. • Determination of PD parameters (levels of circulating total IFN? and markers of its neutralization, namely CXCL9 and CXCL10). • Determination of other relevant disease biomarkers, eg, sCD25 and other exploratory biomarkers. • Measurement of emapalumab concentrations and PD parameters in other matrices, eg, cerebrospinal fluid (CSF), bronchoalveolar lavage fluid (BALF), if clinically appropriate (exploratory). • Level (if any) of circulating antibodies against emapalumab (ADAs). ;Timepoint(s) of evaluation of this end point: See E.5.2.	—

Measure

Time frame

Secondary end point(s): Secondary efficacy endpoints: • Overall Survival, including survival to HSCT and survival after either HSCT or last emapalumab infusion (if HSCT is not performed) • Event-free Survival • Overall Response, i.e., achievement of either Complete or Partial Response or HLH Improvement, at start of conditioning (or at last emapalumab infusion if HSCT is not performed) • Duration of Response, ie, maintenance of response achieved any time during the study (with censoring time at start of conditioning for patients with no events) • Time to Response at any time during the study • Number of patients able to reduce glucocorticoids by 50% or more of baseline dose during emapalumab treatment • Number of patients able to proceed to HSCT, when deemed indicated • QOL indices. Safety endpoints: • Incidence, severity, causality and outcomes of AEs (serious and non-serious). • Evolutions of relevant laboratory parameters, e.g., complete blood cell (CBC) count, liver and renal function tests, and coagulation parameters. • Number of patients who discontinued emapalumab treatment for safety reasons. PK/PD Endpoints: • Serum concentrations of emapalumab to further evaluate emapalumab PK profile. • Determination of PD parameters (levels of circulating total IFN? and markers of its neutralization, namely CXCL9 and CXCL10). • Determination of other relevant disease biomarkers, eg, sCD25 and other exploratory biomarkers. • Measurement of emapalumab concentrations and PD parameters in other matrices, eg, cerebrospinal fluid (CSF), bronchoalveolar lavage fluid (BALF), if clinically appropriate (exploratory). • Level (if any) of circulating antibodies against emapalumab (ADAs). ;Timepoint(s) of evaluation of this end point: See E.5.2.

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Countries

Canada, France, Germany, Italy, Spain, Sweden, Switzerland, United Kingdom, United States

Contacts

Public ContactKarim Jamali

Swedish Orphan Biovitrum AG

Karim.Jamali@sobi.com+41795101898

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026