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

Swedish Orphan Biovitrum35 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Primary Hemophagocytic Lymphohistiocytosis

Interventions

Eligibility

Sex: ALLMax age: 18 Years

Medical Language ↔ Plain English

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.

Locations (27)

Phoenix Children Hospital

Phoenix, Arizona, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Alfred I. duPont Hospital for Children - Nemours Center for Cancer and Blood Disorders - Division of Pediatric Hematology Oncology

Wilmington, Delaware, United States

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Outcomes

Primary Outcomes

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

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

Time frame: Up to Week 8

Secondary Outcomes

Overall Survival at End of Study

Number of patients surviving to the end of the study.

Time frame: Up to 18 months

Overall Survival to HSCT

Number of patients surviving 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

Overall Survival for Patients Receiving HSCT

Number of patients surviving post HSCT.

Time frame: Up to 1 year post HSCT

Event-free Survival

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.

Time frame: Up to 1 year post HSCT

Overall Response at Start of Conditioning

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).

Time frame: Up to 6 months

Duration of Response

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.

Time frame: Up to 18 months

Time to Response

Time to first response at any time during the study.

Time frame: Up to 18 months

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

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

Time frame: Up to 6 months

Number of Patients Proceeding to HSCT

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

Time frame: Up to 18 months

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

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.

Time frame: Up to 6 months

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

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)

Time frame: Up to 6 months

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

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

Time frame: Up to 18 months

Evolution of Laboratory Parameters Change From Baseline to EOT/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

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

Number of Patients Who Discontinued Emapalumab Treatment

Number of patients who discontinued emapalumab treatment for safety reasons.

Time frame: Up to 6 months