Study to Investigate Safety, Efficacy of an Anti-IFNγ mAb in Children With Primary Haemophagocytic Lymphohistiocytosis

NCT01818492 | Completed Phase 2 Results DMC

• 2 other identifiers: NI-0501-042012-003632-23
• Study Type: interventional
• Target: 45
• Locations: 6 countries
• Sites: 20

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.

Conditions

Primary Haemophagocytic Lymphohistiocytosis

Keywords

Emapalumab

Outcome Measures

Primary Outcomes (4)

• Overall Response Rate (ORR) Second Line

  Achievement of either Complete (CR) or Partial Response (PR), or HLH Improvement (HI) at End of Treatment of Study NI 0501-04 (EOT 04), based on pre-specified algorithm. CR: no fever, normal spleen size, no cytopenia (ANC ≥ 1.0x109/L and platelet count ≥ 100x109/L), no hyperferritinemia (serum ferritin \<2000 μg), no coagulopathy (normal D-dimer and/or fibrinogen \>150 mg/dL), no neurological and CSF abnormalities attributed to HLH, no sustained worsening of sCD25. PR: at least 3 HLH clinical and laboratory criteria (including CNS abnormalities) met the CR criteria, no progression of other aspects of HLH disease pathology. HI: improvement (\>50% change from baseline) of at least 3 HLH clinical and laboratory criteria (including CNS involvement).

  End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks)

• Overall Response Rate (ORR) All Treated

  Achievement of either Complete (CR) or Partial Response (PR), or HLH Improvement (HI) at End of Treatment of Study NI 0501-04 (EOT 04), based on pre-specified algorithm. CR: no fever, normal spleen size, no cytopenia (ANC ≥ 1.0x109/L and platelet count ≥ 100x109/L), no hyperferritinemia (serum ferritin \<2000 μg), no coagulopathy (normal D-dimer and/or fibrinogen \>150 mg/dL), no neurological and CSF abnormalities attributed to HLH, no sustained worsening of sCD25. PR: at least 3 HLH clinical and laboratory criteria (including CNS abnormalities) met the CR criteria, no progression of other aspects of HLH disease pathology. HI: improvement (\>50% change from baseline) of at least 3 HLH clinical and laboratory criteria (including CNS involvement).

  End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks)

• Overall Response Rate (ORR) Follow-on Analysis Set:

  Achievement of either Complete (CR) or Partial Response (PR), or HLH Improvement (HI) at End of Treatment of Study NI 0501-04 (EOT 04), based on pre-specified algorithm. CR: no fever, normal spleen size, no cytopenia (ANC ≥ 1.0x109/L and platelet count ≥ 100x109/L), no hyperferritinemia (serum ferritin \<2000 μg), no coagulopathy (normal D-dimer and/or fibrinogen \>150 mg/dL), no neurological and CSF abnormalities attributed to HLH, no sustained worsening of sCD25. PR: at least 3 HLH clinical and laboratory criteria (including CNS abnormalities) met the CR criteria, no progression of other aspects of HLH disease pathology. HI: improvement (\>50% change from baseline) of at least 3 HLH clinical and laboratory criteria (including CNS involvement).

  End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks)

• Overall Response Rate (ORR) at End of Treatment in Study NI-0501-04 (EOT 04) Follow-on Analysis Set: All Treated

  Achievement of either Complete (CR) or Partial Response (PR), or HLH Improvement (HI) at End of Treatment of Study NI 0501-04 (EOT 04), based on pre-specified algorithm. CR: no fever, normal spleen size, no cytopenia (ANC ≥ 1.0x109/L and platelet count ≥ 100x109/L), no hyperferritinemia (serum ferritin \<2000 μg), no coagulopathy (normal D-dimer and/or fibrinogen \>150 mg/dL), no neurological and CSF abnormalities attributed to HLH, no sustained worsening of sCD25. PR: at least 3 HLH clinical and laboratory criteria (including CNS abnormalities) met the CR criteria, no progression of other aspects of HLH disease pathology. HI: improvement (\>50% change from baseline) of at least 3 HLH clinical and laboratory criteria (including CNS involvement).

  End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks)

Secondary Outcomes (7)

• Time to Response

  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)

• Durability of First Response

  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)

• Overall Survival

  Time from the date of first dose to last dose, or 8 weeks after first dose.

• Number of Patients Able to Reduce Glucocorticoids

  End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks.

• Cumulative Duration of Response

  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)

Study Arms (1)

NI-0501

EXPERIMENTAL

NI-0501 administered by IV infusion at a starting dose of 1 mg/kg.

Biological: NI-0501

Interventions

NI-0501 BIOLOGICAL

NI-0501

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Swedish Orphan Biovitrum: lead
• Seventh Framework Programme: collaborator

Study Sites (20)

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, 02115, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Cincinnati Children's Hospital - Division of Immunobiology - Department of Pediatrics

Cincinnati, Ohio, 45229-3039, United States

Location

Texas Children's Cancer Center

Houston, Texas, 77030, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

University Children's Hospital

Münster, 48149, Germany

Location

Azienda Ospedaliero Universitaria Meyer

Florence, 50139, Italy

Location

Istituto Giannina Gaslini

Genoa, 16147, Italy

Location

Azienda Ospedaliera San Gerardo

Monza, 20900, Italy

Location

Azienda Ospedaliera Padova - Clinica di Oncoematologia Pediatrica

Padua, 35128, Italy

Location

Ospedale Pediatrico Bambino Gesu'

Roma, 00165, Italy

Location

Ospedale Donna Bambino - U.O.C. Oncoematologia Pediatrica

Verona, 37126, Italy

Location

Hospital Sant Joan de Déu

Barcelona, 08950, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 119-129, Spain

Location

Hospital Universitario Niño Jesús

Madrid, 28009, Spain

Location

Karolinska University Hospital

Stockholm, 17176, Sweden

Location

Great Ormond Street Hospital - Department of Haematology

London, WC1N 3JH, United Kingdom

Location

Related Publications (2)

• Brossard P, Laveille C. Population Pharmacokinetics of the Anti-Interferon-Gamma Monoclonal Antibody Emapalumab: An Updated Analysis. Rheumatol Ther. 2024 Jun;11(3):869-880. doi: 10.1007/s40744-024-00669-y. Epub 2024 Apr 25.

  PMID: 38662147 DERIVED

• 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.

  PMID: 32374962 DERIVED

Related Links

• NI-0501-05, long-term follow-up study description on clinicaltrials.gov

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: Carl Johan Treutiger
• Organization: Sobi AB

CarlJohan.Treutiger@sobi.com

46 76 00 11 815

Study Officials

• Radmila Kanceva, MD

  Swedish Orphan Biovitrum

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2013
• First Posted: March 26, 2013
• Study Start: July 1, 2013
• Primary Completion: January 1, 2019
• Study Completion: January 1, 2019
• Last Updated: February 21, 2023
• Results First Posted: September 4, 2020

Record last verified: 2021-04

Locations

DE (1); US (8); ES (3); SE (1); GB (1); IT (6)