Study to Assess the Efficacy and Safety of Emapalumab in Primary Haemophagocytic Lymphohistiocytosis
- Registration Number
- NCT03312751
- Lead Sponsor
- Swedish Orphan Biovitrum
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 35
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Emapalumab Emapalumab -
- Primary Outcome Measures
Name Time Method Overall Response at Week 8 or End of Treatment (if Earlier) 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 Outcome Measures
Name Time Method Overall Survival to HSCT 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.
Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) Up to 18 months Incidence of adverse events. SAE = serious adverse event; TEAE = treatment-emergent adverse event
Quality of Life Assessed Through PedsQL™, Pediatric Quality of Life Inventory™ 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.
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 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, fibrinogenOverall Survival for Patients Receiving HSCT Up to 1 year post HSCT Number of patients surviving post HSCT.
Overall Response at Start of Conditioning 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).
Event-free Survival 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.
Time to Response Up to 18 months Time to first response at any time during the study.
Number of Patients Reducing Glucocorticoids by 50% or More of the Baseline Dose During Emapalumab Treatment Up to 6 months Number of patients able to reduce glucocorticoids by 50% or more of the baseline dose during emapalumab treatment.
Overall Survival at End of Study Up to 18 months Number of patients surviving to the end of the study.
Duration of Response 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.
Number of Patients Proceeding to HSCT Up to 18 months Number of patients able to proceed to HSCT when deemed indicated.
Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) 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)Number of Patients Who Discontinued Emapalumab Treatment Up to 6 months Number of patients who discontinued emapalumab treatment for safety reasons.
Trial Locations
- Locations (27)
Texas Children's Hospital - Feigin Center
🇺🇸Houston, Texas, United States
Cincinnati Children's Hospital
🇺🇸Cincinnati, Ohio, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Hospital for Sick Children
🇨🇦Toronto, Canada
Children's and Women's Health Centre of British Columbia
🇨🇦Vancouver, Canada
Universitätsklinikum Essen
🇩🇪Essen, Germany
Medical Center- University of Freiburg
🇩🇪Freiburg, Germany
Universitätsklinikum Eppendorf
🇩🇪Hamburg, Germany
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario Niño Jesús
🇪🇸Madrid, Spain
Karolinska University Hospital Huddinge
🇸🇪Stockholm, Sweden
Great Ormond Street Hospital
🇬🇧London, United Kingdom
Leeds Children's Hospital
🇬🇧Leeds, United Kingdom
Royal Manchester Children's Hospital
🇬🇧Manchester, United Kingdom
University Children's Hospital Zurich
🇨🇭Zürich, Switzerland
Dana-Farber Cancer Institute (DFCI)
🇺🇸Boston, Massachusetts, United States
Alfred I. duPont Hospital for Children - Nemours Center for Cancer and Blood Disorders - Division of Pediatric Hematology Oncology
🇺🇸Wilmington, Delaware, United States
Spectrum Health Helen DeVos Children's Hospital
🇺🇸Grand Rapids, Michigan, United States
Istituto Giannina Gaslini
🇮🇹Genova, Italy
Fondazione MBBM, Ospedale San Gerardo
🇮🇹Monza, Italy
Ospedale Pediatrico Bambino Gesù
🇮🇹Rome, Italy
Ospedale della Donna e del Bambino
🇮🇹Verona, Italy
Hopital Ste-Justine Research Center
🇨🇦Montréal, Canada
Phoenix Children Hospital
🇺🇸Phoenix, Arizona, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Children's Healthcare of Atlanta
🇺🇸Atlanta, Georgia, United States