Back to resultsStudy to Assess the Efficacy and Safety of Emapalumab in Primary Haemophagocytic Lymphohistiocytosis
Primary Purpose
Primary Hemophagocytic Lymphohistiocytosis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Emapalumab
Sponsored by
About this trial
This is an interventional treatment trial for Primary Hemophagocytic Lymphohistiocytosis focused on measuring Interferon-gamma, NI-0501, primary HLH, emapalumab
Eligibility Criteria
Inclusion Criteria:
- Primary HLH patients with active disease.
- Treatment naïve patients or patients having already received HLH conventional therapy, but having failed or unable to tolerate current standard of care.
- Informed consent signed by the patient or by the patient's legally authorized representative.
- Guidance on contraception
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.
Sites / Locations
- Phoenix Children Hospital
- Children's Hospital Los Angeles
- Children's Hospital Colorado
- Alfred I. duPont Hospital for Children - Nemours Center for Cancer and Blood Disorders - Division of Pediatric Hematology Oncology
- Children's Healthcare of Atlanta
- Dana-Farber Cancer Institute (DFCI)
- Spectrum Health Helen Devos Children's Hospital
- Cincinnati Children's Hospital
- Texas Children's Cancer Center
- Seattle Children's Hospital
- Hopital Ste-Justine Research Center
- Hospital for Sick Children
- Children's and Women's Health Centre of British Columbia
- Universitätsklinikum Essen
- Medical Center- University of Freiburg
- Universitätsklinikum Eppendorf
- Istituto Giannina Gaslini
- Fondazione MBBM, Ospedale San Gerardo
- Ospedale Pediatrico Bambino Gesu
- Ospedale della Donna e del Bambino
- Hospital Universitario Vall d'Hebron
- Hospital Universitario Niño Jesús
- Karolinska University Hospital Huddinge
- University Children's Hospital Zurich
- Leeds Children Hospital
- Great Ormond Street Hospital
- Royal Manchester Children's Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Emapalumab
Arm Description
Outcomes
Primary Outcome Measures
Overall Response at Week 8 or End of Treatment (if earlier)
Number of patients achieving either Complete or Partial Response or HLH Improvement, at Week 8 or EOT (whichever occurs earlier).
Secondary Outcome Measures
Overall Survival
Number of patients surviving, including survival to HSCT and survival after either HSCT or last emapalumab infusion (if HSCT was not performed).
Event-free Survival
The duration of event-free survival was defined as time from HSCT to date of (whichever occurs first): death from any cause, graft failure, or HLH reactivation.
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).
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.
Time to Response
Time to first response at any time during the study.
Number of Patients Reducing Glucocorticoids by 50% or More
Number of patients able to reduce glucocorticoids by 50% or more of the baseline dose during emapalumab treatment.
Number of Patients Proceeding to HSCT
Number of patients able to proceed to HSCT when deemed indicated.
Change in PedsQL Score
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.
Change in BASES Score
Assessment of the quality of life using BASES, the Behavioral, Affective and Somatic Experiences questionnaires. The BASES questionnaire 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.
BASES subscale scores were calculated using a 5-point Likert scale from 1 to 5 for all items and they will be weighted equally to calculate subscale scores for the following domains:
Physical Discomfort (5 items - where 1 is considered best response)
Cooperation/Compliance (5 items - where 1 is considered best response)
Mood/Behavior (7 items - where 5 is considered best response)
Quality of Interactions (3 items - where 1 is considered best response)
Activity/Sleep (2 items - where 5 is considered best response for patient's activity level and 1 is considered best response for patient's sleeping)
Incidence, Severity, Causality and Outcomes of AEs (serious and non-serious)
Incidence of adverse events.
Evolution of Laboratory Parameters
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), 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], prothrombin time), D-dimer, fibrinogen
Number of Patients who Discontinued Emapalumab Treatment
Number of patients who discontinued emapalumab treatment for safety reasons.
Full Information
NCT ID
NCT03312751
First Posted
October 5, 2017
Last Updated
June 15, 2023
Sponsor
Swedish Orphan Biovitrum
1. Study Identification
Unique Protocol Identification Number
NCT03312751
Brief Title
Study to Assess the Efficacy and Safety of Emapalumab in Primary Haemophagocytic Lymphohistiocytosis
Official 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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
February 6, 2019 (Actual)
Primary Completion Date
August 18, 2021 (Actual)
Study Completion Date
September 14, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Swedish Orphan Biovitrum
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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, with special focus 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Hemophagocytic Lymphohistiocytosis
Keywords
Interferon-gamma, NI-0501, primary HLH, emapalumab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Emapalumab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Emapalumab
Intervention Description
Emapalumab will be administered by intravenous infusion, twice weekly.
Primary Outcome Measure Information:
Title
Overall Response at Week 8 or End of Treatment (if earlier)
Description
Number 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 Outcome Measure Information:
Title
Overall Survival
Description
Number of patients surviving, including survival to HSCT and survival after either HSCT or last emapalumab infusion (if HSCT was not performed).
Time Frame
Up to 18 months
Title
Event-free Survival
Description
The duration of event-free survival 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 18 months
Title
Overall Response at Start of Conditioning
Description
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
Title
Duration of Response
Description
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.
Time Frame
Up to 18 months
Title
Time to Response
Description
Time to first response at any time during the study.
Time Frame
Up to 18 months
Title
Number of Patients Reducing Glucocorticoids by 50% or More
Description
Number of patients able to reduce glucocorticoids by 50% or more of the baseline dose during emapalumab treatment.
Time Frame
Up to 6 months
Title
Number of Patients Proceeding to HSCT
Description
Number of patients able to proceed to HSCT when deemed indicated.
Time Frame
Up to 18 months
Title
Change in PedsQL Score
Description
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
Title
Change in BASES Score
Description
Assessment of the quality of life using BASES, the Behavioral, Affective and Somatic Experiences questionnaires. The BASES questionnaire 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.
BASES subscale scores were calculated using a 5-point Likert scale from 1 to 5 for all items and they will be weighted equally to calculate subscale scores for the following domains:
Physical Discomfort (5 items - where 1 is considered best response)
Cooperation/Compliance (5 items - where 1 is considered best response)
Mood/Behavior (7 items - where 5 is considered best response)
Quality of Interactions (3 items - where 1 is considered best response)
Activity/Sleep (2 items - where 5 is considered best response for patient's activity level and 1 is considered best response for patient's sleeping)
Time Frame
Up to 6 months
Title
Incidence, Severity, Causality and Outcomes of AEs (serious and non-serious)
Description
Incidence of adverse events.
Time Frame
Up to 18 months
Title
Evolution of Laboratory Parameters
Description
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), 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], prothrombin time), D-dimer, fibrinogen
Time Frame
Up to 6 months
Title
Number of Patients who Discontinued Emapalumab Treatment
Description
Number of patients who discontinued emapalumab treatment for safety reasons.
Time Frame
Up to 6 months
Other Pre-specified Outcome Measures:
Title
Serum Concentrations of Emapalumab
Description
The serum concentration of emapalumab will be measured as a function of time to determine the emapalumab PK profile.
Time Frame
Up to Week 8
Title
Change in Pharmacodynamic Parameters
Description
Levels (in ng/L) of total IFNγ, markers of its neutralization (CXCL9 and CXCL10), and sCD25.
Time Frame
Up to 18 months
Title
Number of Patients Who Demonstrated a Presence of Circulating Antibodies Against Emapalumab to Determine Immunogenicity
Description
The presence of circulating antibodies against emapalumab was inferred by positive results for anti-drug antibodies (ADAs).
Time Frame
Up to 18 months
10. Eligibility
Sex
All
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
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.
Facility Information:
Facility Name
Phoenix Children Hospital
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045-7106
Country
United States
Facility Name
Alfred I. duPont Hospital for Children - Nemours Center for Cancer and Blood Disorders - Division of Pediatric Hematology Oncology
City
Wilmington
State/Province
Delaware
ZIP/Postal Code
19803
Country
United States
Facility Name
Children's Healthcare of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30329
Country
United States
Facility Name
Dana-Farber Cancer Institute (DFCI)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Spectrum Health Helen Devos Children's Hospital
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Facility Name
Cincinnati Children's Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Texas Children's Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Hopital Ste-Justine Research Center
City
Montréal
ZIP/Postal Code
QC H3T 1C5
Country
Canada
Facility Name
Hospital for Sick Children
City
Toronto
ZIP/Postal Code
ON M5G 1X8
Country
Canada
Facility Name
Children's and Women's Health Centre of British Columbia
City
Vancouver
ZIP/Postal Code
V6H 3V4
Country
Canada
Facility Name
Universitätsklinikum Essen
City
Essen
ZIP/Postal Code
45122
Country
Germany
Facility Name
Medical Center- University of Freiburg
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Universitätsklinikum Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Istituto Giannina Gaslini
City
Genova
ZIP/Postal Code
16147
Country
Italy
Facility Name
Fondazione MBBM, Ospedale San Gerardo
City
Monza
ZIP/Postal Code
20900
Country
Italy
Facility Name
Ospedale Pediatrico Bambino Gesu
City
Rome
ZIP/Postal Code
00165
Country
Italy
Facility Name
Ospedale della Donna e del Bambino
City
Verona
ZIP/Postal Code
37126
Country
Italy
Facility Name
Hospital Universitario Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitario Niño Jesús
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Facility Name
Karolinska University Hospital Huddinge
City
Stockholm
ZIP/Postal Code
14186
Country
Sweden
Facility Name
University Children's Hospital Zurich
City
Zürich
ZIP/Postal Code
CH-8032
Country
Switzerland
Facility Name
Leeds Children Hospital
City
Leeds
ZIP/Postal Code
LS13EX
Country
United Kingdom
Facility Name
Great Ormond Street Hospital
City
London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
Facility Name
Royal Manchester Children's Hospital
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Study to Assess the Efficacy and Safety of Emapalumab in Primary Haemophagocytic Lymphohistiocytosis
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