A Study of Emicizumab Administered Subcutaneously (SC) in Pediatric Participants With Hemophilia A and Factor VIII (FVIII) Inhibitors

NCT ID: NCT02795767

Last Updated: 2021-06-02

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

88 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-07-22

Study Completion Date

2020-11-11

Brief Summary

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This non-randomized, multicenter, open-label, Phase III clinical study will evaluate the efficacy, safety, and pharmacokinetics of emicizumab administered subcutaneously initially once weekly (QW) in pediatric participants with hemophilia A with FVIII inhibitors. This study will open two additional non-randomized cohorts to investigate once every 2 weeks (Q2W) and once every 4 weeks (Q4W) regimens in pediatric participants.

Detailed Description

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Conditions

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Hemophilia A

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort A: 1.5 mg/kg Emicizumab QW

Participants will receive emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurs first.

Group Type EXPERIMENTAL

Emicizumab

Intervention Type DRUG

Emicizumab will be administered as per the schedule specified in the respective arm.

Cohort B: 3 mg/kg Emicizumab Q2W

Participants will receive emicizumab at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 3 mg/kg every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurs first.

Group Type EXPERIMENTAL

Emicizumab

Intervention Type DRUG

Emicizumab will be administered as per the schedule specified in the respective arm.

Cohort C: 6 mg/kg Emicizumab Q4W

Participants will receive emicizumab at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 6 mg/kg every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurs first.

Group Type EXPERIMENTAL

Emicizumab

Intervention Type DRUG

Emicizumab will be administered as per the schedule specified in the respective arm.

Interventions

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Emicizumab

Emicizumab will be administered as per the schedule specified in the respective arm.

Intervention Type DRUG

Other Intervention Names

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Hemlibra RO5534262 RG6013 ACE910

Eligibility Criteria

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Inclusion Criteria

* Children less than (\<) 12 years of age, with allowance for participants 12 to 17 years of age who weigh \<40 kilograms (kg) (Cohort A only); and participants \<2 years of age will be allowed to participate only after the protocol-defined interim data review criteria are met (Cohort A only)
* Diagnosis of congenital hemophilia A of any severity and documented history of high-titer inhibitor (that is \[i.e.\], greater than or equal to \[\>/=\] 5 bethesda units \[BU\])
* Requires treatment with bypassing agents
* Adequate hematologic, hepatic, and renal function

Exclusion Criteria

* Inherited or acquired bleeding disorder other than hemophilia A
* Ongoing (or planning to receive during the study) immune tolerance induction (ITI) therapy or prophylaxis treatment with FVIII
* Previous (in the past 12 months) or current treatment for thromboembolic disease or signs of thromboembolic disease
* Other disease that may increase risk of bleeding or thrombosis
* History of clinically significant hypersensitivity associated with monoclonal antibody therapy or components of the emicizumab injection
* Known infection with human immunodeficiency virus (HIV) or hepatitis B or C virus
* Use of systemic immunomodulators at enrollment or planned use during the study period
* Planned surgery (excluding minor procedures such as tooth extraction or incision and drainage) during the study
* Inability (or unwillingness by caregiver) to receive (allow receipt of) blood or blood products (or any standard-of-care treatment for a life-threatening condition)
* Participants who are at high risk for thrombotic microangiopathy (TMA) (e.g., have a previous medical or family history of TMA), in the investigator's judgement
Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Chugai Pharmaceutical

INDUSTRY

Sponsor Role collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

University of Colorado Denver, Children's Hospital

Aurora, Colorado, United States

Site Status

Children'S Healthcare of Atlanta

Atlanta, Georgia, United States

Site Status

Rush Medical Center

Chicago, Illinois, United States

Site Status

Children's Hospital of Michigan; Pediatrics

Detroit, Michigan, United States

Site Status

North Shore/Long Island Jewish PRIME; Pediatric Hematology/Oncology & Stem Cell Transplantation

New Hyde Park, New York, United States

Site Status

Oregon Health & Science Uni ; Dept of Pediatrics

Portland, Oregon, United States

Site Status

Bloodworks Northwest (formerly Puget Sound Blood Center); Hemophilia

Seattle, Washington, United States

Site Status

ICIC

San José, , Costa Rica

Site Status

Hopital Cardio-vasculaire Louis Pradel; Hemostase clinique

Bron, , France

Site Status

CH de Bicetre; Centre de Traitement d' Hemophilie

Le Kremlin-Bicêtre, , France

Site Status

Groupe Hospitalier Necker Enfants Malades

Paris, , France

Site Status

Universitätsklinikum Bonn; Institut für Experimentelle Hämatologie und Transfusionsmedizin

Bonn, , Germany

Site Status

IRCCS Ca' Granda Ospedale Maggiore Policlinico; Centro Emofilia e Trombosi "Angelo Bianchi e Bonomi"

Milan, Lombardy, Italy

Site Status

Nagoya University Hospital

Aichi, , Japan

Site Status

Hospital of the University of Occupational and Environmental Health,Japan

Kitakyushu-shi, , Japan

Site Status

Nara Medical University Hospital

Nara, , Japan

Site Status

Shizuoka Children's Hospital

Shizuoka, , Japan

Site Status

Ogikubo Hospital

Tokyo, , Japan

Site Status

Charlotte Maxeke Johannesburg Hospital; Haemophilia Comprehensive Care Center

Johannesburg, , South Africa

Site Status

Hospital Universitario la Paz; Servicio de Hematologia

Madrid, , Spain

Site Status

Hospital Universitario Virgen del Rocio; Servicio de Hematologia

Seville, , Spain

Site Status

Hospital Universitario la Fe; Servicio de Hematologia

Valencia, , Spain

Site Status

Adana Acibadem Hospital; Pediatric Hematology

Adana, , Turkey (Türkiye)

Site Status

Istanbul Uni Istanbul Medical Faculty

Istanbul, , Turkey (Türkiye)

Site Status

Istanbul University, Cerrahpasa Medical Faculty; Pediatrics Department

Istanbul, , Turkey (Türkiye)

Site Status

Ege University, School of Medicine; Pediatrics Department

Izmir, , Turkey (Türkiye)

Site Status

Great Ormond street Hospital for Children NHS Foundation Trust; Haemophilia Centre

London, , United Kingdom

Site Status

Countries

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United States Costa Rica France Germany Italy Japan South Africa Spain Turkey (Türkiye) United Kingdom

References

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Kruse-Jarres R, Peyvandi F, Oldenburg J, Chang T, Chebon S, Doral MY, Croteau SE, Lambert T, Kempton CL, Pipe SW, Ko RH, Trzaskoma B, Dhalluin C, Bienz NS, Niggli M, Lehle M, Paz-Priel I, Young G, Jimenez-Yuste V. Surgical outcomes in people with hemophilia A taking emicizumab prophylaxis: experience from the HAVEN 1-4 studies. Blood Adv. 2022 Dec 27;6(24):6140-6150. doi: 10.1182/bloodadvances.2022007458.

Reference Type DERIVED
PMID: 35939785 (View on PubMed)

Young G, Liesner R, Chang T, Sidonio R, Oldenburg J, Jimenez-Yuste V, Mahlangu J, Kruse-Jarres R, Wang M, Uguen M, Doral MY, Wright LY, Schmitt C, Levy GG, Shima M, Mancuso ME. A multicenter, open-label phase 3 study of emicizumab prophylaxis in children with hemophilia A with inhibitors. Blood. 2019 Dec 12;134(24):2127-2138. doi: 10.1182/blood.2019001869.

Reference Type DERIVED
PMID: 31697801 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2016-000073-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BH29992

Identifier Type: -

Identifier Source: org_study_id

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