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Completed

NCT Number: NCT03312751

Study to Assess the Efficacy and Safety of Emapalumab in Primary Haemophagocytic Lymphohistiocytosis

The purpose of this study is to expand the knowledge on the efficacy and safety of emapalumab (previously known as NI-0501) as a treatment for primary haemophagocytic lymphohistiocytosis (HLH) patients, including on long-term outcomes and quality of life assessments. Emapalumab can be administered as the first-line therapy to patients not previously treated with the current standard of care, or can be given to patients who have either failed or were unable to tolerate the available standard of care.

Emapalumab is to be administered until the start of conditioning for hematopoietic stem cell transplantation (HSCT), with an anticipated duration ranging from a minimum of 4 weeks to approximately 12 weeks and not exceeding 6 months.

After treatment completion, patients will continue in the study for long-term follow-up until 1 year after either HSCT or last emapalumab infusion (if HSCT is not performed).

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Key information

Conditions

Primary Hemophagocytic Lymphohistiocytosis Hemic and Lymphatic Diseases Histiocytosis Histiocytosis, Non-Langerhans-Cell Lymphatic Diseases Lymphohistiocytosis, Hemophagocytic

Age range

Up to 18 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hopital Ste-Justine Research Center, Montreal, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Main Inclusion Criteria:

  • Primary HLH patients with active disease.
  • Treatment naïve patients or patients having already received HLH conventional therapy, but having not responded, not achieved a satisfactory response or worsened, or reactivated, or are unable to tolerate current standard of care.
  • Informed consent signed by the patient or by the patient's legally authorized representative.
  • Received guidance on contraception.

Main Exclusion Criteria:

  • Diagnosis of secondary HLH consequent to a proven rheumatic, metabolic or neoplastic disease.
  • Active mycobacteria, Histoplasma capsulatum, Shigella, Salmonella, Campylobacter or Leishmania infections.
  • Evidence of latent tuberculosis.
  • Presence of malignancy.
  • 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.
  • History of hypersensitivity or allergy to any component of the study regimen.
  • Receipt of a BCG vaccine within 12 weeks prior to Screening.
  • Receipt of a live or attenuated-live (other than BCG) vaccine within 6 weeks prior to Screening.
  • Pregnant or lactating female patients.

Treatment and study plan

Emapalumab

Drug

Emapalumab will be administered by intravenous infusion, twice weekly.

Primary outcomes

  1. Overall Response at Week 8 or End of Treatment (if Earlier)

    Time frame: Up to Week 8

    The overall response rate (ORR) of patients achieving either Complete or Partial Response or HLH Improvement, at Week 8 or EOT (whichever occurs earlier).

Secondary outcomes

  1. Overall Survival at End of Study

    Time frame: Up to 18 months

    Number of patients surviving to the end of the study.

  2. Overall Survival to HSCT

    Time frame: From start of treatment to HSCT or from start of treatment until 1 year after EOT for patient who did not undergo HSCT

    Number of patients surviving to HSCT.

  3. Overall Survival for Patients Receiving HSCT

    Time frame: Up to 1 year post HSCT

    Number of patients surviving post HSCT.

  4. Event-free Survival

    Time frame: Up to 1 year post HSCT

    Number of patients experiencing event-free survival, the duration of which was defined as time from HSCT to date of (whichever occurs first): death from any cause, graft failure, or HLH reactivation.

  5. Overall Response at Start of Conditioning

    Time frame: Up to 6 months

    Number of patients achieving either a Complete or Partial Response or HLH Improvement, at start of conditioning (or at last emapalumab infusion if HSCT is not performed).

  6. Duration of Response

    Time frame: Up to 18 months

    Duration of response, i.e., maintenance of the response achieved at any time during the study (with censoring time at start of conditioning for patients with no event) calculated only for patients showing confirmed overall response. Summarized by number of patients experiencing each category of response duration.

  7. Time to Response

    Time frame: Up to 18 months

    Time to first response at any time during the study.

  8. Number of Patients Reducing Glucocorticoids by 50% or More of the Baseline Dose During Emapalumab Treatment

    Time frame: Up to 6 months

    Number of patients able to reduce glucocorticoids by 50% or more of the baseline dose during emapalumab treatment.

  9. Number of Patients Proceeding to HSCT

    Time frame: Up to 18 months

    Number of patients able to proceed to HSCT when deemed indicated.

  10. Quality of Life Assessed Through PedsQL™, Pediatric Quality of Life Inventory™

    Time frame: Up to 6 months

    Assessment of the quality of life using the PedsQL "Pediatric Quality of Life Inventory". The PedsQL uses a 100-point scale ranging from 0 to 100 with higher values indicating better quality of life.

  11. Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES)

    Time frame: Up to 6 months

    Assessment of the quality of life using the BASES questionnaire, which is a validated 38-item questionnaire; a reduced nonvalidated 22-item version of the questionnaire is used in an exploratory nature for the secondary endpoint.

    Subscale scores were calculated using a 5-point Likert scale from 1 to 5 for all questions. Scores for all questions in each subscale were added up and divided by the number of patients in the analysis population to reach the mean score. Subscale scores were calculated for the following domains:

    • Physical Discomfort (5 questions, '1' = best response, total range 5-25)
    • Cooperation/Compliance (5 questions, '1' = best response, total range 5-25)
    • Mood/Behavior (7 questions, '5' = best response, total range 7-35)
    • Quality of Interactions (3 questions, '1' = best response, total range 3-15)
    • Activity/Sleep (2 questions, '5' = best response for patient's activity level and '1' = best response for patient's sleeping, total range 2-10)

  12. Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious)

    Time frame: Up to 18 months

    Incidence of adverse events. SAE = serious adverse event; TEAE = treatment-emergent adverse event

  13. Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8

    Time frame: To Week 8 or End of treatment if before Week 8.

    Number of patients experiencing shifts from baseline in the following relevant laboratory parameters are reported:

    • Biochemistry: glucose ferritin, C-reactive protein (CRP), liver function (alkaline phosphatase [ALP], alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma glutamyl transferase [γGT], lactate dehydrogenase [LDH], bilirubin, renal function (albumin, creatinine, urea, urea nitrogen), triglycerides
    • Complete blood count: basophils, basophils/leukocytes, eosinophils, eosinophils/leukocytes, hematocrit, hemoglobin, large unstained cells, lymphocytes, lymphocytes/leukocytes, monocytes, monocytes/leukocytes, neutrophils band form, neutrophils band form/leukocytes, platelets, erythrocytes, leukocytes
    • Coagulation tests (activated partial thromboplastin time [aPTT], aPTT ratio, prothrombin time, prothrombin international normalized ratio [INR]), D-dimer, fibrinogen

  14. Number of Patients Who Discontinued Emapalumab Treatment

    Time frame: Up to 6 months

    Number of patients who discontinued emapalumab treatment for safety reasons.

Other outcomes

  1. Serum Concentrations of Emapalumab

    Time frame: Up to Week 8, with data presented at Baseline and EOT/W8

    The serum concentration of emapalumab will be measured as a function of time to determine the emapalumab PK profile.

  2. Change in Pharmacodynamic Parameters

    Time frame: Up to 18 months with data presented at Baseline and EOT/W8

    Levels (in ng/L) of total IFNγ (interferon gamma), markers of its neutralization (CXCL9 and CXCL10), and sCD25.

  3. Number of Patients Who Demonstrated a Presence of Circulating Antibodies Against Emapalumab to Determine Immunogenicity

    Time frame: Up to 1 year follow up post end of treatment with assessments at first dose of emapalumab, Week 4, Week 8, EOT and following treatment at day 100 and at the 1 year follow up visit, with data presented at study day 21 and EOT/Week 8.

    The presence of circulating antibodies against emapalumab was inferred by positive results for anti-drug antibodies (ADAs).

Sponsors and collaborators

Lead sponsor

Swedish Orphan Biovitrum

Industry

Registry information

Official study title

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

Important dates

Study start
2019
Primary completion
2021
Study completion
2022
First posted
Oct 18, 2017
Registry last updated
Mar 12, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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