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

NCT ID: NCT01818492

Last Updated: 2023-02-21

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-07-31

Study Completion Date

2019-01-31

Brief Summary

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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

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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.

Conditions

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Primary Haemophagocytic Lymphohistiocytosis

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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NI-0501

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

Group Type EXPERIMENTAL

NI-0501

Intervention Type BIOLOGICAL

Interventions

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NI-0501

Intervention Type BIOLOGICAL

Eligibility Criteria

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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
Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Seventh Framework Programme

OTHER

Sponsor Role collaborator

Swedish Orphan Biovitrum

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Radmila Kanceva, MD

Role: STUDY_DIRECTOR

Swedish Orphan Biovitrum

Locations

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Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

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

Wilmington, Delaware, United States

Site Status

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Site Status

Dana-Farber Cancer Institute (DFCI)

Boston, Massachusetts, United States

Site Status

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

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

Cincinnati, Ohio, United States

Site Status

Texas Children's Cancer Center

Houston, Texas, United States

Site Status

Primary Children's Hospital

Salt Lake City, Utah, United States

Site Status

University Children's Hospital

Münster, , Germany

Site Status

Azienda Ospedaliero Universitaria Meyer

Florence, , Italy

Site Status

Istituto Giannina Gaslini

Genoa, , Italy

Site Status

Azienda Ospedaliera San Gerardo

Monza, , Italy

Site Status

Azienda Ospedaliera Padova - Clinica di Oncoematologia Pediatrica

Padua, , Italy

Site Status

Ospedale Pediatrico Bambino Gesu'

Roma, , Italy

Site Status

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

Verona, , Italy

Site Status

Hospital Sant Joan de Déu

Barcelona, , Spain

Site Status

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Universitario Niño Jesús

Madrid, , Spain

Site Status

Karolinska University Hospital

Stockholm, , Sweden

Site Status

Great Ormond Street Hospital - Department of Haematology

London, , United Kingdom

Site Status

Countries

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United States Germany Italy Spain Sweden United Kingdom

References

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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.

Reference Type DERIVED
PMID: 38662147 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32374962 (View on PubMed)

Provided Documents

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Document Type: Study Protocol: US protocol

View Document

Document Type: Study Protocol: EU protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://www.clinicaltrials.gov/ct2/show/NCT02069899

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

Other Identifiers

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2012-003632-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NI-0501-04

Identifier Type: -

Identifier Source: org_study_id

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