A Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Emicizumab in Participants From Birth to 12 Months of Age With Hemophilia A Without Inhibitors

NCT ID: NCT04431726

Last Updated: 2025-10-20

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-04
• Study Completion Date: 2030-05-18

Brief Summary

This is a Phase IIIb, multicenter, open-label, single-arm study of prophylactic emicizumab in previously untreated and minimally treated patients at study enrollment from birth to ≤12 months of age with severe hemophilia A (intrinsic factor VIII [FVIII] level <1%) without FVIII inhibitors. The study is designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of emicizumab administered at 3 milligrams per kilogram of body weight (mg/kg) once every 2 weeks (Q2W) for 52 weeks. After 1 year of treatment, participants will continue to receive emicizumab (1.5 mg/kg once every week [QW], 3 mg/kg Q2W or 6 mg/kg once every 4 weeks [Q4W]) over a 7-year long-term follow-up period under this study frame.

Conditions

Severe Hemophilia A

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Emicizumab

Group Type: EXPERIMENTAL

Emicizumab

Intervention Type: DRUG

Initially, all participants will receive 4 loading doses of 3 milligrams per kilogram (mg/kg) emicizumab subcutaneously (SC) once every week (QW) for 4 weeks followed by the maintenance dosing regimen 3 mg/kg emicizumab SC once every 2 weeks (Q2W) for a total of 52 weeks. Starting from Week 17 of treatment, individual participants may have their dose up-titrated to 3 mg/kg SC QW if they experience suboptimal bleeding control.

At the Week 53 clinic visit following consultation with the treating physician, parents/caregivers may elect for their child to continue with the maintenance 3-mg/kg SC Q2W dosing regimen or to switch to the maintenance 1.5-mg/kg SC QW or 6-mg/kg SC once every 4 weeks (Q4W) dosing regimen for the subsequent 7-year long-term follow-up period.

During the study, participants will be treated with emicizumab until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria specified in the protocol, whichever occurs first.

Interventions

Emicizumab

Initially, all participants will receive 4 loading doses of 3 milligrams per kilogram (mg/kg) emicizumab subcutaneously (SC) once every week (QW) for 4 weeks followed by the maintenance dosing regimen 3 mg/kg emicizumab SC once every 2 weeks (Q2W) for a total of 52 weeks. Starting from Week 17 of treatment, individual participants may have their dose up-titrated to 3 mg/kg SC QW if they experience suboptimal bleeding control.

At the Week 53 clinic visit following consultation with the treating physician, parents/caregivers may elect for their child to continue with the maintenance 3-mg/kg SC Q2W dosing regimen or to switch to the maintenance 1.5-mg/kg SC QW or 6-mg/kg SC once every 4 weeks (Q4W) dosing regimen for the subsequent 7-year long-term follow-up period.

During the study, participants will be treated with emicizumab until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria specified in the protocol, whichever occurs first.

Intervention Type: DRUG

Other Intervention Names

Hemlibra; RO5534262; RG6013; ACE910

Eligibility Criteria

Inclusion Criteria

• Age from birth to ≤12 months at time of informed consent
• Body weight ≥3 kilograms (kg) at time of informed consent. Patients with a lower body weight can be enrolled after they have reached a body weight of 3 kg. Premature babies (gestational age <38 weeks) may be enrolled as long as they have reached a body weight of 3 kg. For premature babies, the corrected gestational age should be reported.
• Mandatory receipt of vitamin K prophylaxis according to local standard practice
• Diagnosis of severe congenital hemophilia A (intrinsic FVIII level <1%)
• A negative test for FVIII inhibitor (i.e., <0.6 Bethesda units [BU]/mL) locally assessed during the 2-week screening period
• No history of documented FVIII inhibitor (i.e., <0.6 BU/mL), FVIII drug-elimination half-life <6 hours, or FVIII recovery <66%
• Previously untreated patients or minimally treated patients (i.e., up to 5 days of exposure with hemophilia-related treatments, such as plasma-derived FVIII, recombinant FVIII, fresh frozen plasma, cryoprecipitate, or whole blood products)
• Documentation of the details of the hemophilia-related treatments received since birth
• Documentation of the details of the bleeding episodes since birth
• For patients from birth to <3 months of age at the time of study entry: no evidence of active intracranial hemorrhage, as confirmed by a negative cranial ultrasound at screening irrespective of delivery mode
• Adequate hematologic, hepatic, and renal function, as defined in the protocol
• For parents/caregivers: willingness and ability to comply with the study protocol requirements, scheduled visits, treatment plans, laboratory tests, completion of applicable questionnaires, and other study procedures

Exclusion Criteria

• Inherited or acquired bleeding disorder other than severe hemophilia A
• Use of systemic immunomodulators (e.g., interferon) at enrollment or planned use during the study
• Receipt of any of the following: Prior use of emicizumab prophylaxis including investigational or commercial emicizumab; An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 drug-elimination half-lives of last drug administration; A non-hemophilia-related investigational drug within the last 30 days or 5 drug-elimination half-lives, whichever is shorter; An investigational drug concurrently
• Current active severe bleed, such as intracranial hemorrhage
• Planned surgery (excluding minor procedures, e.g., circumcision, CVAD placement) during the study
• History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
• Patients who are at high risk for thrombotic microangiopathy (TMA) (e.g., have a previous medical or family history of TMA, such as thrombotic thrombocytopenic purpura, atypical hemolytic uremic syndrome) in the investigator's judgment
• Previous or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis in patients for whom anti-thrombotic treatment is not currently ongoing) or signs of thromboembolic disease
• Any hereditary or acquired maternal condition that may predispose the patient to thrombotic events (e.g., inherited thrombophilias antiphospholipid syndrome)
• Other diseases (e.g., certain autoimmune diseases) that may increase risk of bleeding or thrombosis
• Known infection with HIV, hepatitis B virus, or hepatitis C virus
• Serious infection requiring antibiotics or antiviral treatments within 14 days prior to screening
• Concurrent disease, treatment, abnormality in clinical laboratory tests, vital signs measurements, or physical examination findings that could interfere with the conduct of the study or that would, in the opinion of the investigator or Sponsor, preclude the patient's safe participation in and completion of the study or interpretation of the study results
• Unwillingness of the parent or caregiver to allow receipt of blood or blood products, or any standard-of-care treatment for a life-threatening condition
• Any other medical, social, or other condition that may prevent adequate compliance with the study protocol in the opinion of the investigator

• Minimum Eligible Age: 0 Months
• Maximum Eligible Age: 12 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Phoenix Children's Hospital

Phoenix, Arizona, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

University of Colorado Denver, Children's Hospital

Aurora, Colorado, United States

Tulane University Health Sciences Center

New Orleans, Louisiana, United States

University of Michigan

Ann Arbor, Michigan, United States

Seattle Children's Hospital

Seattle, Washington, United States

The Children's Hospital at Westmead

Westmead, New South Wales, Australia

Royal Children's Hospital

Parkville, Victoria, Australia

Perth Children's Hospital

Nedlands, Western Australia, Australia

Medizinische Universität Wien

Vienna, , Austria

Cliniques Universitaires St-Luc

Brussels, , Belgium

UZ Leuven Gasthuisberg

Leuven, , Belgium

Hospital das Clínicas Faculdades Médicas de Ribeirão Preto

Ribeirão Preto, São Paulo, Brazil

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

The Hospital for Sick Children

Toronto, Ontario, Canada

Groupe Hospitalier Necker Enfants Malades

Paris, , France

Universitätsklinikum Bonn

Bonn, , Germany

Hämophilie-Zentrum Rhein Main GmbH

Mörfelden-Walldorf, , Germany

Sheba Medical Center - National Hemophilia Center

Tel Litwinsky, , Israel

AORN Santobono Pausilipon

Napoli, Campania, Italy

AOU di Parma

Parma, Emilia-Romagna, Italy

AOU Careggi

Florence, Tuscany, Italy

Charlotte Maxeke Johannesburg Hospital

Johannesburg, , South Africa

Hospital Sant Joan de Deu

Esplugues de Llobregat, Barcelona, Spain

Hospital Universitario la Paz

Madrid, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Adana Acibadem Hospital

Adana, , Turkey (Türkiye)

Hacettepe University Medical Faculty

Ankara, , Turkey (Türkiye)

Ege University, School of Medicine

Izmir, , Turkey (Türkiye)

Ondokuz Mayis Univ. Med. Fac.

Samsun, , Turkey (Türkiye)

Queen Elizabeth University Hospital

Glasgow, , United Kingdom

Countries

United States; Australia; Austria; Belgium; Brazil; Canada; France; Germany; Israel; Italy; South Africa; Spain; Turkey (Türkiye); United Kingdom

References

Pipe SW, Collins P, Dhalluin C, Kenet G, Schmitt C, Buri M, Jimenez-Yuste V, Peyvandi F, Young G, Oldenburg J, Mancuso ME, Kavakli K, Kiialainen A, Deb S, Niggli M, Chang T, Lehle M, Fijnvandraat K. Emicizumab prophylaxis in infants with hemophilia A (HAVEN 7): primary analysis of a phase 3b open-label trial. Blood. 2024 Apr 4;143(14):1355-1364. doi: 10.1182/blood.2023021832.

Reference Type: DERIVED

PMID: 38127586 (View on PubMed)

Lopez-Jaime FJ, Benitez O, Diaz Jordan BL, Montano A, Coll J, Quintana Paris L, Gomez-Del Castillo Solano MDC. Expert opinion paper on the treatment of hemophilia a with emicizumab. Hematology. 2023 Dec;28(1):2166334. doi: 10.1080/16078454.2023.2166334.

Reference Type: DERIVED

PMID: 36636993 (View on PubMed)

Hart DP. Commentary on "Development of a novel fully functional coagulation factor VIII with reduced immunogenicity utilizing an in silico prediction and deimmunization approach" - Will we ever be able to avoid inhibitor formation in hemophilia A? J Thromb Haemost. 2021 Sep;19(9):2125-2126. doi: 10.1111/jth.15404. No abstract available.

Reference Type: DERIVED

PMID: 34435432 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-001733-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-505964-13-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

MO41787

Identifier Type: -

Identifier Source: org_study_id