A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Prophylactic Emicizumab Versus no Prophylaxis in Hemophilia A Participants With Inhibitors

Brief Title

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Prophylactic Emicizumab Versus no Prophylaxis in Hemophilia A Participants With Inhibitors

Official Title

A Randomized, Multicenter, Open-Label, Phase III Clinical Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of Prophylactic Emicizumab Versus no Prophylaxis in Hemophilia A Patients With Inhibitors

Brief Summary

      This multicenter, open-label study will evaluate the safety, efficacy and pharmacokinetics of
      prophylactic emicizumab treatment in participants previously treated with episodic or
      prophylactic bypassing agents. Episodic bypassing agent participants will be randomized in a
      2:1 fashion to receive emicizumab prophylaxis (Arm A) versus no prophylaxis (Arm B) and will
      be stratified across Arms A and B according to the number of bleeds they experienced over the
      last 24 weeks prior to study entry (less than [<] 9 or greater than or equal to [>/=] 9
      bleeds); Arm B participants will have the opportunity to switch to emicizumab prophylaxis
      after at least 24 weeks on-study. Prophylactic bypassing agent participants will switch to
      emicizumab prophylaxis (Arm C) from the start of the trial; enrollment will be extended for
      24 weeks after the last participant has enrolled in Arms A or B or until approximately 50
      participants have enrolled in Arm C, whichever occurs first. Episodic bypassing agent
      participants who previously participated in the non-interventional study BH29768
      (NCT02476942) who were unable to enroll in Arms A or B, or participants on prophylactic
      bypassing agents who were unable to enroll in Arm C, prior to their closure will have the
      opportunity to enroll in Arm D. Like participants in Arms A and C, Arm D participants will
      receive emicizumab prophylaxis from the start of the trial. All participants will continue to
      receive episodic bypassing agent therapy to treat breakthrough bleeds, preferably with
      recombinant activated factor VII (rFVIIa).

Study Phase

Phase 3

Study Type

Interventional

Primary Outcome

Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis

Secondary Outcome

 Model-Based Annualized Bleed Rate (ABR) for All Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis

Condition

Hemophilia A

Intervention

Emicizumab

Study Arms / Comparison Groups

 Arm A: 1.5 mg/kg Emicizumab QW

Description:  Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Drug

Estimated Enrollment

Start Date

November 18, 2015

Completion Date

December 1, 2020

Primary Completion Date

October 25, 2016

Eligibility Criteria

        Inclusion Criteria:

          -  Body weight >/= 40 kilograms (kg) at the time of screening

          -  Diagnosis of congenital hemophilia A of any severity and documented history of
             high-titer inhibitor ( that is [i.e.], >/= 5 Bethesda Units [BU])

          -  Documentation of treatment with episodic or prophylactic bypassing agents for at least
             the last 24 weeks

          -  >/= 6 bleeds in the last 24 weeks prior to screening (if on an episodic bypassing
             agent regimen) or >/=2 bleeds in the last 24 weeks prior to screening (if on a
             prophylactic bypassing agent regimen)

          -  Adequate hematologic, hepatic and renal function

          -  For women who are not postmenopausal or surgically sterile: agreement to remain
             abstinent or use single or combined highly effective contraceptive methods

        Exclusion Criteria:

          -  Participants with inherited or acquired bleeding disorder other than hemophilia A

          -  Participants with ongoing (or plan to receive during the study) immune tolerance
             induction therapy or prophylaxis with Factor VIII (FVIII), with the exception of
             participants who have received a treatment regimen of FVIII prophylaxis with
             concurrent bypassing agent prophylaxis

          -  Previous (in the past 12 months) or current treatment for thromboembolic disease (with
             the exception of previous catheter-associated thrombosis for which antithrombotic
             treatment is not currently ongoing) or current signs of thromboembolic disease

          -  Participants with other conditions (for example [e.g.], certain autoimmune diseases)
             that may increase the risk of bleeding or thrombosis

          -  History of clinically significant hypersensitivity associated with monoclonal antibody
             therapies or components of the emicizumab injection

          -  Known human immunodeficiency virus (HIV) infection with cluster of differentiation 4
             (CD4) count < 200 cells per microliter (cells/mcL) within 24 weeks prior to screening

          -  Use of systemic immunomodulators (e.g., interferon or rituximab) at enrolment or
             planned use during the study, with the exception of antiretroviral therapy

          -  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 judgment

          -  Concurrent disease, treatment, or abnormality in clinical laboratory tests that could
             interfere with the conduct of the study or that would, in the opinion of the
             investigator or Sponsor, preclude the participant's safe participation in and
             completion of the study or interpretation of the study results

          -  Planned surgery (excluding minor procedures such as tooth extraction or incision and
             drainage) during the study

          -  Receipt of emicizumab in a prior investigational study; An investigational drug to
             treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug
             administration; A non-hemophilia-related investigational drug within last 30 days or 5
             half-lives, whichever is shorter; An investigational drug concurrently

          -  Unwillingness to use highly effective contraception methods for the specified duration
             in the protocol (females only, unless required otherwise by the local health
             authority)

          -  Clinically significant abnormality on screening evaluations or laboratory tests that,
             in the opinion of the investigator, may pose an additional risk in administering study
             drug to the participant

          -  Pregnancy or lactation, or intent to become pregnant during the study

Gender

All

Ages

12 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Clinical Trials, ,

Location Countries

Australia

Location Countries

Australia

Administrative Informations

NCT ID

NCT02622321

Organization ID

BH29884

Secondary IDs

2015-002866-21

Responsible Party

Sponsor

Study Sponsor

Hoffmann-La Roche

Collaborators

 Chugai Pharmaceutical

Study Sponsor

Clinical Trials, Study Director, Hoffmann-La Roche

Verification Date

May 2021