Clinical trial NCT03312751: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Hemophagocytic Lymphohistiocytosis
Keywords: Interferon-gamma
NI-0501
primary HLH
emapalumab
Lead sponsor: Swedish Orphan Biovitrum
Sponsor class: INDUSTRY
First posted: 2017-10-18
Enrollment: 35
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Overall Response at Week 8 or End of Treatment (if Earlier)
timeFrame: Up to Week 8
Secondary outcomes:
measure: Overall Survival at End of Study
timeFrame: Up to 18 months
measure: Overall Survival to HSCT
timeFrame: From start of treatment to HSCT or from start of treatment until 1 year after EOT for patient who did not undergo HSCT
measure: Overall Survival for Patients Receiving HSCT
timeFrame: Up to 1 year post HSCT
measure: Event-free Survival
timeFrame: Up to 1 year post HSCT
measure: Overall Response at Start of Conditioning
timeFrame: Up to 6 months
measure: Duration of Response
timeFrame: Up to 18 months
measure: Time to Response
timeFrame: Up to 18 months
measure: Number of Patients Reducing Glucocorticoids by 50% or More of the Baseline Dose During Emapalumab Treatment
timeFrame: Up to 6 months
measure: Number of Patients Proceeding to HSCT
timeFrame: Up to 18 months
measure: Quality of Life Assessed Through PedsQL™, Pediatric Quality of Life Inventory™
timeFrame: Up to 6 months
measure: Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES)
timeFrame: Up to 6 months
measure: Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious)
timeFrame: Up to 18 months
measure: Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8
timeFrame: To Week 8 or End of treatment if before Week 8.
measure: Number of Patients Who Discontinued Emapalumab Treatment
timeFrame: Up to 6 months
Other outcomes:
measure: Serum Concentrations of Emapalumab
timeFrame: Up to Week 8, with data presented at Baseline and EOT/W8
measure: Change in Pharmacodynamic Parameters
timeFrame: Up to 18 months with data presented at Baseline and EOT/W8
measure: Number of Patients Who Demonstrated a Presence of Circulating Antibodies Against Emapalumab to Determine Immunogenicity
timeFrame: 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.
Locations:
city: Phoenix
country: United States
facility: Phoenix Children Hospital
state: Arizona
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Wilmington
country: United States
facility: Alfred I. duPont Hospital for Children - Nemours Center for Cancer and Blood Disorders - Division of Pediatric Hematology Oncology
state: Delaware
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Boston
country: United States
facility: Dana-Farber Cancer Institute (DFCI)
state: Massachusetts
city: Grand Rapids
country: United States
facility: Spectrum Health Helen DeVos Children's Hospital
state: Michigan
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Houston
country: United States
facility: Texas Children's Hospital - Feigin Center
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Montréal
country: Canada
facility: Hopital Ste-Justine Research Center
city: Toronto
country: Canada
facility: Hospital for Sick Children
city: Vancouver
country: Canada
facility: Children's and Women's Health Centre of British Columbia
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Freiburg
country: Germany
facility: Medical Center- University of Freiburg
city: Hamburg
country: Germany
facility: Universitätsklinikum Eppendorf
city: Genova
country: Italy
facility: Istituto Giannina Gaslini
city: Monza
country: Italy
facility: Fondazione MBBM, Ospedale San Gerardo
city: Rome
country: Italy
facility: Ospedale Pediatrico Bambino Gesù
city: Verona
country: Italy
facility: Ospedale della Donna e del Bambino
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Niño Jesús
city: Stockholm
country: Sweden
facility: Karolinska University Hospital Huddinge
city: Zürich
country: Switzerland
facility: University Children's Hospital Zurich
city: Leeds
country: United Kingdom
facility: Leeds Children's Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
Study officials:
References: