Clinical trial NCT01818492: Study to Investigate Safety, Efficacy of an Anti-IFNγ mAb in Children With Primary Haemophagocytic Lymphohistiocytosis
Official title: A Phase 2/3 Open-label Single Arm Multicentre Study to Assess Safety Tolerability Pharmacokinetics and Efficacy of i.v. Administrations of NI-0501 an Anti-IFNγ mAb in Paediatric Patients With Primary Haemophagocytic Lymphohistiocytosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Primary Haemophagocytic Lymphohistiocytosis
Keywords: Emapalumab
Lead sponsor: Swedish Orphan Biovitrum
Sponsor class: INDUSTRY
Collaborators: name: Seventh Framework Programme
First posted: 2013-03-26
Enrollment: 45
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 assess the safety, tolerability and efficacy of a new drug aimed at controlling disease activity in patients diagnosed with primary haemophagocytic lymphohistiocytosis. The new drug 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 current standard of care. Administration will be on top of a glucocorticosteroid, which is usually part of the current recommended treatment.

Detailed description: The purpose of this study is to assess the safety, tolerability and efficacy of a new drug aimed at controlling disease activity in patients diagnosed with primary haemophagocytic lymphohistiocytosis. The new drug 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 current standard of care. Administration will be on top of a glucocorticosteroid, which is usually part of the current recommended treatment.

All participants in the NI-0501-04 study (NCT01818492) were invited to participate in the long-term follow-up study NI-0501-05 (NCT02069899). For the primary completion date, mentioned here, we refer to the NI-0501-04 study, even though in accordance with the NI-0501-04 study objectives, namely the assessment of long-term efficacy and safety endpoints, the study analyses also included data collected in the long-term follow-up study NI-0501-05. Hence these data are reported together. Study NI-0501-05 accepts patients from NI-0501-04 and NI-0501-06. Data collection for the patients from NI-0501-04 is completed.

The primary efficacy and safety analyses are based on the regulatory cut-off date of 20 July 2017. Refer to the publication in N Engl J Med 2020 May 7; 382 (19):1811-1822. Follow-on analyses have been conducted on all patients enrolled in the study, i.e. including the patients enrolled after the cut-off date of 20 July 2017. The results reported here refer to the totality of the 45 patients enrolled.

Eligibility criteria: Inclusion Criteria:

* Gender: male and female
* Age: up to and including 18 years at diagnosis of Haemophagocytic Lymphohistiocytosis
* Primary HLH patients
* Patient (if ≥ 18 years old), or patient's legal representative(s) must have signed informed consent

Exclusion Criteria:

* Diagnosis of secondary Haemophagocytic Lymphohistiocytosis consequent to a proven rheumatic or neoplastic disease.
* Body weight \< 3 kg.
* Patients treated with biologics within a specific timeframe
* Active Mycobacteria, Histoplasma Capsulatum, Shigella, Salmonella, Campylobacter and Leishmania infections.
* Presence of malignancy.
* Concomitant disease or malformation severely affecting the cardiovascular, pulmonary, liver or renal function

Primary outcomes:
measure: Overall Response Rate (ORR) Second Line
timeFrame: End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks)
measure: Overall Response Rate (ORR) All Treated
timeFrame: End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks)
measure: Overall Response Rate (ORR) Follow-on Analysis Set:
timeFrame: End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks)
measure: Overall Response Rate (ORR) at End of Treatment in Study NI-0501-04 (EOT 04) Follow-on Analysis Set: All Treated
timeFrame: End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks)
Secondary outcomes:
measure: Time to Response
timeFrame: Assessed up to End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks)
measure: Durability of First Response
timeFrame: Assessed up to End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks)
measure: Overall Survival
timeFrame: Time from the date of first dose to last dose, or 8 weeks after first dose.
measure: Number of Patients Able to Reduce Glucocorticoids
timeFrame: End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks.
measure: Cumulative Duration of Response
timeFrame: up to start of HSCT conditioning, whenever HSCT conditioning is scheduled (at least 4 weeks after treatment start), or End of Treatment 04/05 (if the patient did not have HSCT performed)
measure: Survival Pre-HSCT
timeFrame: Assessed up to HSCT, whenever HSCT occurred (up to approximately 6 months after treatment initiation)
measure: Survival Post-HSCT
timeFrame: Assessed up to Last Observation (up to 1 year after transplant, or up to approximately 18 months after treatment initiation)
Other outcomes:
Locations:
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: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital - Division of Immunobiology - Department of Pediatrics
state: Ohio
city: Houston
country: United States
facility: Texas Children's Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Münster
country: Germany
facility: University Children's Hospital
city: Florence
country: Italy
facility: Azienda Ospedaliero Universitaria Meyer
city: Genoa
country: Italy
facility: Istituto Giannina Gaslini
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo
city: Padua
country: Italy
facility: Azienda Ospedaliera Padova - Clinica di Oncoematologia Pediatrica
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesu'
city: Verona
country: Italy
facility: Ospedale Donna Bambino - U.O.C. Oncoematologia Pediatrica
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Déu
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
city: London
country: United Kingdom
facility: Great Ormond Street Hospital - Department of Haematology
Study officials:
affiliation: Swedish Orphan Biovitrum
name: Radmila Kanceva, MD
role: STUDY_DIRECTOR
References:
citation: Locatelli F, Jordan MB, Allen C, Cesaro S, Rizzari C, Rao A, Degar B, Garrington TP, Sevilla J, Putti MC, Fagioli F, Ahlmann M, Dapena Diaz JL, Henry M, De Benedetti F, Grom A, Lapeyre G, Jacqmin P, Ballabio M, de Min C. Emapalumab in Children with Primary Hemophagocytic Lymphohistiocytosis. N Engl J Med. 2020 May 7;382(19):1811-1822. doi: 10.1056/NEJMoa1911326.