Primary Hemophagocytic LymphohistiocytosisPhase 3NCT03312751
Study to Assess the Efficacy and Safety of Emapalumab in Primary Haemophagocytic Lymphohistiocytosis
A Phase 3 study testing Emapalumab in people with Primary Hemophagocytic Lymphohistiocytosis, run by Swedish Orphan Biovitrum at 27 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Primary Hemophagocytic Lymphohistiocytosis
- What is being tested?
- Emapalumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 27 sitesin 8 countries
- Study dates
- 6 Feb 2019to 14 Sep 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
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.
Trial locations and contacts
27 sites in 8 countries.
27 sites in 8 countries
United States10 sites
Children's Healthcare of Atlanta
Atlanta, Georgia, 30329
Children's Hospital Colorado
Aurora, Colorado, 80045-7106
Dana-Farber Cancer Institute (DFCI)
Boston, Massachusetts, 02215
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229
Spectrum Health Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503
Texas Children's Hospital - Feigin Center
Houston, Texas, 77030
Children's Hospital Los Angeles
Los Angeles, California, 90027
Phoenix Children Hospital
Phoenix, Arizona, 85016
Seattle Children's Hospital
Seattle, Washington, 98109
Alfred I. duPont Hospital for Children - Nemours Center for Cancer and Blood Disorders - Division of Pediatric Hematology Oncology
Wilmington, Delaware, 19803
Italy4 sites
Istituto Giannina Gaslini
Genova, 16147
Fondazione MBBM, Ospedale San Gerardo
Monza, 20900
Ospedale Pediatrico Bambino Gesù
Rome, 00165
Ospedale della Donna e del Bambino
Verona, 37126
Canada3 sites
Hopital Ste-Justine Research Center
Montreal, QC H3T 1C5
Hospital for Sick Children
Toronto, ON M5G 1X8
Children's and Women's Health Centre of British Columbia
Vancouver, V6H 3V4
Germany3 sites
Universitätsklinikum Essen
Essen, 45147
Medical Center- University of Freiburg
Freiburg im Breisgau, 79106
Universitätsklinikum Eppendorf
Hamburg, 20246
United Kingdom3 sites
Leeds Children's Hospital
Leeds, LS1 3EX
Great Ormond Street Hospital
London, WC1N 3JH
Royal Manchester Children's Hospital
Manchester, M13 9WL
Spain2 sites
Hospital Universitario Vall d'Hebron
Barcelona, 08035
Hospital Universitario Niño Jesús
Madrid, 28009
About this study
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
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).
- Being tested
- Emapalumab
- Keywords
- Interferon-gamma, NI-0501, primary HLH, emapalumab
- Medical subject headings
- Lymphohistiocytosis, Hemophagocytic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EmapalumabDrug
Emapalumab will be administered by intravenous infusion, twice weekly.
| Study group | Role | What they receive |
|---|---|---|
| Emapalumab | Experimental | Not described Receives: Drug: Emapalumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Up to Week 8
Secondary outcomes (14)
Overall Survival at End of Study
Number of patients surviving to the end of the study.
Measured: Up to 18 months
Overall Survival to HSCT
Number of patients surviving to HSCT.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: Up to 18 months
Time to Response
Time to first response at any time during the study.
Measured: 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.
Measured: Up to 6 months
Number of Patients Proceeding to HSCT
Number of patients able to proceed to HSCT when deemed indicated.
Measured: 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.
Measured: 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)
Measured: 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
Measured: 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
Measured: 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.
Measured: Up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2017
- Study start6 Feb 2019
- Primary completion18 Aug 2021
- Study completion14 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Primary Hemophagocytic LymphohistiocytosisStudies of the same condition, open and under way.
- More trials run by Swedish Orphan BiovitrumThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Swedish Orphan Biovitrum
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03312751
- Sponsor's protocol ID
- NI-0501-09
- Status last verified
- Mar 2024
- First submitted
- 5 Oct 2017
- Last updated
- 12 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03312751
- Acronym / sponsor ID
- NI-0501-09
- Keywords
- Interferon-gamma, NI-0501, primary HLH, emapalumab
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Swedish Orphan BiovitrumIndustry (pharma, biotech, devices)
- Study start
- 6 Feb 2019 (actual)
- Primary completion
- 18 Aug 2021 (actual)
- Study completion
- 14 Sep 2022 (actual)
- First posted
- 18 Oct 2017 (actual)
- Results
- Posted 12 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Emapalumab | Experimental | Drug: Emapalumab |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EmapalumabEmapalumab will be administered by intravenous infusion, twice weekly. | Drug | Emapalumab |
Primary outcome
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).
14 secondary outcomes
Overall Survival at End of Study
Time frame: Up to 18 months
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
Overall Survival for Patients Receiving HSCT
Time frame: Up to 1 year post HSCT
Event-free Survival
Time frame: Up to 1 year post HSCT
Overall Response at Start of Conditioning
Time frame: Up to 6 months
Duration of Response
Time frame: Up to 18 months
Time to Response
Time frame: Up to 18 months
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 Proceeding to HSCT
Time frame: Up to 18 months
Quality of Life Assessed Through PedsQL™, Pediatric Quality of Life Inventory™
Time frame: Up to 6 months
Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES)
Time frame: Up to 6 months
Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious)
Time frame: Up to 18 months
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 Who Discontinued Emapalumab Treatment
Time frame: Up to 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
27 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Emapalumab in people with Primary Hemophagocytic Lymphohistiocytosis, run by Swedish Orphan Biovitrum at 27 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States, Italy, Canada, Germany, United Kingdom and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response at Week 8 or End of Treatment (if Earlier) (time frame: Up to Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2024; AzTrials last refreshed its copy on 8 Nov 2026.