Study to Assess the Efficacy and Safety of Emapalumab in Primary Haemophagocytic Lymphohistiocytosis

NCT03312751 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: NI-0501-09
• Study Type: interventional
• Target: 35
• Locations: 8 countries
• Sites: 27

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).

Conditions

Primary Hemophagocytic Lymphohistiocytosis

Keywords

Interferon-gamma; NI-0501; primary HLH; emapalumab

Outcome Measures

Primary Outcomes (1)

• 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).

  Up to Week 8

Secondary Outcomes (14)

• Overall Survival at End of Study

  Up to 18 months

• 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

• Overall Survival for Patients Receiving HSCT

  Up to 1 year post HSCT

• Event-free Survival

  Up to 1 year post HSCT

• Overall Response at Start of Conditioning

  Up to 6 months

Other Outcomes (3)

• Serum Concentrations of Emapalumab

  Up to Week 8, with data presented at Baseline and EOT/W8

• Change in Pharmacodynamic Parameters

  Up to 18 months with data presented at Baseline and EOT/W8

• Number of Patients Who Demonstrated a Presence of Circulating Antibodies Against Emapalumab to Determine Immunogenicity

  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.

Study Arms (1)

Emapalumab

EXPERIMENTAL

Drug: Emapalumab

Interventions

Emapalumab DRUG

Emapalumab will be administered by intravenous infusion, twice weekly.

Emapalumab

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Swedish Orphan Biovitrum: lead

Study Sites (27)

Phoenix Children Hospital

Phoenix, Arizona, 85016, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045-7106, United States

Location

Alfred I. duPont Hospital for Children - Nemours Center for Cancer and Blood Disorders - Division of Pediatric Hematology Oncology

Wilmington, Delaware, 19803, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30329, United States

Location

Dana-Farber Cancer Institute (DFCI)

Boston, Massachusetts, 02215, United States

Location

Spectrum Health Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Texas Children's Hospital - Feigin Center

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98109, United States

Location

Hopital Ste-Justine Research Center

Montreal, QC H3T 1C5, Canada

Location

Hospital for Sick Children

Toronto, ON M5G 1X8, Canada

Location

Children's and Women's Health Centre of British Columbia

Vancouver, V6H 3V4, Canada

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Medical Center- University of Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Universitätsklinikum Eppendorf

Hamburg, 20246, Germany

Location

Istituto Giannina Gaslini

Genova, 16147, Italy

Location

Fondazione MBBM, Ospedale San Gerardo

Monza, 20900, Italy

Location

Ospedale Pediatrico Bambino Gesù

Rome, 00165, Italy

Location

Ospedale della Donna e del Bambino

Verona, 37126, Italy

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Niño Jesús

Madrid, 28009, Spain

Location

Karolinska University Hospital Huddinge

Stockholm, 14186, Sweden

Location

University Children's Hospital Zurich

Zurich, CH-8032, Switzerland

Location

Leeds Children's Hospital

Leeds, LS1 3EX, United Kingdom

Location

Great Ormond Street Hospital

London, WC1N 3JH, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, M13 9WL, United Kingdom

Location

MeSH Terms

Conditions

Lymphohistiocytosis, Hemophagocytic

Interventions

Emapalumab

Condition Hierarchy (Ancestors)

Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Radmila Kanceva, MD, Medicine Development Lead
• Organization: Swedish Orphan Biovitrum AG

Radmila.Kanceva@sobi.com

+41 793048899

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2017
• First Posted: October 18, 2017
• Study Start: February 6, 2019
• Primary Completion: August 18, 2021
• Study Completion: September 14, 2022
• Last Updated: March 12, 2024
• Results First Posted: March 12, 2024

Record last verified: 2024-03

Locations

GB (3); SE (1); CH (1); ES (2); IT (4); DE (3); US (10); CA (3)