A Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Emicizumab Given Every 4 Weeks in Participants With Hemophilia A

NCT ID: NCT03020160

Last Updated: 2023-01-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-30
• Study Completion Date: 2022-06-29

Brief Summary

This multicenter, open-label, non-randomized study will assess the efficacy, safety, pharmacokinetics, and pharmacodynamics of emicizumab administered at a dose of 6 milligrams per kilogram (mg/kg) every 4 weeks in participants with hemophilia A with or without inhibitors against factor VIII (FVIII). The study consists of 2 parts: a pharmacokinetic (PK) run-in part followed by an expansion part.

Conditions

Hemophilia A

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Emicizumab: PK Run-in Cohort

Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks, with no loading dose, for at least 24 weeks.

Group Type: EXPERIMENTAL

Emicizumab

Intervention Type: DRUG

Emicizumab will be administered according to dose and schedule described in respective arms. After at least 24 weeks on prophylactic emicizumab, individuals who experienced suboptimal bleeding control on emicizumab (according to protocol-defined criteria) had the opportunity to increase their dose to 3 mg/kg weekly. Upon implementation of protocol Version 5 (20-Dec-2019), treatment duration was extended. During this study prolongation, participants had the opportunity to switch to a preferred emicizumab dosing regimen (1.5 mg/kg weekly, 3 mg/kg every 2 weeks, or 6 mg/kg every 4 weeks) in order to provide them the same flexibility as with commercial product.

Emicizumab: Expansion Cohort

Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks for at least 24 weeks.

Group Type: EXPERIMENTAL

Emicizumab

Intervention Type: DRUG

Emicizumab will be administered according to dose and schedule described in respective arms. After at least 24 weeks on prophylactic emicizumab, individuals who experienced suboptimal bleeding control on emicizumab (according to protocol-defined criteria) had the opportunity to increase their dose to 3 mg/kg weekly. Upon implementation of protocol Version 5 (20-Dec-2019), treatment duration was extended. During this study prolongation, participants had the opportunity to switch to a preferred emicizumab dosing regimen (1.5 mg/kg weekly, 3 mg/kg every 2 weeks, or 6 mg/kg every 4 weeks) in order to provide them the same flexibility as with commercial product.

Interventions

Emicizumab

Emicizumab will be administered according to dose and schedule described in respective arms. After at least 24 weeks on prophylactic emicizumab, individuals who experienced suboptimal bleeding control on emicizumab (according to protocol-defined criteria) had the opportunity to increase their dose to 3 mg/kg weekly. Upon implementation of protocol Version 5 (20-Dec-2019), treatment duration was extended. During this study prolongation, participants had the opportunity to switch to a preferred emicizumab dosing regimen (1.5 mg/kg weekly, 3 mg/kg every 2 weeks, or 6 mg/kg every 4 weeks) in order to provide them the same flexibility as with commercial product.

Intervention Type: DRUG

Other Intervention Names

Hemlibra; RO5534262; ACE910

Eligibility Criteria

Inclusion Criteria

• Body weight greater than or equal to (>/=) 40 kilograms (kg) at screening
• Diagnosis of severe congenital hemophilia A or hemophilia A with FVIII inhibitors
• Participants using rFVIIa or willing to switch to recombinant activated factor VII (rFVIIa) as primary bypassing agent for the treatment of breakthrough bleeds
• FVIII inhibitor test during screening with titer results available prior to first administration of study drug
• Participants without FVIII inhibitors, that is with less than (<) 0.6 Bethesda unit per milliliter [BU/mL];< 1.0 BU/mL only for laboratories with an historical sensitivity cutoff for inhibitor detection of 1.0 BU/mL, who completed successful immune tolerance induction (ITI) must have done so at least 5 years before screening and must have no evidence of inhibitor recurrence (permanent or temporary) indicated by detection of an inhibitor greater than (>) 0.6 BU/mL (> 1.0 BU/mL only for laboratories with an historical sensitivity cutoff for inhibitor detection of 1.0 BU/mL) since ITI
• Adequate hematologic, hepatic, and renal function

Exclusion Criteria

• Inherited or acquired bleeding disorder other than hemophilia A
• Ongoing or planned ITI therapy; participants in whom ITI has failed will be eligible with a 72-hour washout period prior to the first emicizumab administration
• History of illicit drug or alcohol abuse within 48 weeks prior to screening, in the investigator's judgment
• Participants who are at high risk for thrombotic microangiopathy (TMA) (for example, have a previous medical or family history of TMA), in the investigator's judgment
• Previous (within the last 12 months) or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing) or signs of thromboembolic disease
• Other conditions (for example, certain autoimmune diseases) that may currently increase the risk of bleeding or thrombosis
• History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
• Known HIV infection with cluster of differentiation (CD) 4 cells counts <200 cells per microliter (cells/mcL)
• Use of systemic immunomodulators (for example, interferon) at enrollment or planned use during the study, with the exception of anti-retroviral therapy
• Concomitant disease, condition, significant abnormality on screening evaluations or laboratory tests, or treatment that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an additional unacceptable risk in administering study drug to the participant
• Pregnancy or lactation or intention to become pregnant during the study
• Women with a positive serum pregnancy test result within 7 days prior to initiation of study drug

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chugai Pharmaceutical

INDUSTRY

Sponsor Role: collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

University of California Davis

Sacramento, California, United States

Indiana Hemophilia & Thrombosis center

Indianapolis, Indiana, United States

University of Michigan, C.S. Mott Children's Hospital

Ann Arbor, Michigan, United States

Univ of N Carolina Chapel Hill; Hematology/Oncology

Chapel Hill, North Carolina, United States

Royal Brisbane Hospital; Clinical Haematology

Brisbane, Queensland, Australia

Royal Adelaide Hospital; Haematology Clinical Trials

Adelaide, South Australia, Australia

Cliniques Universitaires St-Luc

Brussels, , Belgium

UZ Leuven Gasthuisberg

Leuven, , Belgium

Hokkaido University Hospital

Hokkaido, , Japan

Nara Medical University Hospital

Nara, , Japan

National Center for Child Health and Development

Tokyo, , Japan

Tokyo Medical University Hospital

Tokyo, , Japan

Instytut Hematologii i Transfuzjologii; Klinika Zaburzeń Hemostazy i Chorób Wewnętrznych

Warsaw, , Poland

Uniwersytecki Szpital Kliniczny; Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku

Wroclaw, , Poland

Hospital Universitario la Paz; Servicio de Hematologia

Madrid, , Spain

Hospital Universitario Virgen del Rocio; Servicio de Hematologia

Seville, , Spain

Hospital Universitario la Fe; Servicio de Hematologia

Valencia, , Spain

Countries

United States; Australia; Belgium; Japan; Poland; Spain

References

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)

Pipe SW, Shima M, Lehle M, Shapiro A, Chebon S, Fukutake K, Key NS, Portron A, Schmitt C, Podolak-Dawidziak M, Selak Bienz N, Hermans C, Campinha-Bacote A, Kiialainen A, Peerlinck K, Levy GG, Jimenez-Yuste V. Efficacy, safety, and pharmacokinetics of emicizumab prophylaxis given every 4 weeks in people with haemophilia A (HAVEN 4): a multicentre, open-label, non-randomised phase 3 study. Lancet Haematol. 2019 Jun;6(6):e295-e305. doi: 10.1016/S2352-3026(19)30054-7. Epub 2019 Apr 16.

Reference Type: DERIVED

PMID: 31003963 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-001094-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BO39182

Identifier Type: -

Identifier Source: org_study_id