Brief Title
Efficacy, Safety, and Pharmacokinetic Study of Prophylactic Emicizumab Versus No Prophylaxis in Hemophilia A Participants
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
Brief Summary
This multicenter, open-label, Phase 3 study with randomized and non-randomized arms is
designed to investigate the efficacy, safety, and pharmacokinetics of emicizumab in
participants with hemophilia A regardless of factor VIII (FVIII) inhibitor status.
Participants greater than or equal to (≥)12 years old who received episodic therapy with
FVIII or bypassing agents prior to study entry and experienced at least 5 bleeds over the
prior 24 weeks will be randomized in a 2:2:1 ratio to the following regimens: Arm A:
Emicizumab prophylaxis at 3 milligrams per kilogram (mg/kg) once every week (QW)
subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg QW SC; Arm B: Emicizumab prophylaxis
at 3 mg/kg QW SC for 4 weeks, followed by 6 mg/kg once every 4 weeks (Q4W) SC; and Arm C: No
prophylaxis (control arm). In addition, pediatric participants less than (<)12 years old with
hemophilia A and FVIII inhibitors who received episodic therapy with bypassing agents prior
to study entry will be enrolled to Arm D: Emicizumab prophylaxis at 3 mg/kg QW SC for 4
weeks, followed by 1.5 mg/kg QW SC.
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Model-Based Annualized Bleeding Rate for Treated Bleeds
Secondary Outcome
Model-Based Annualized Bleeding Rate for All Bleeds (Whether Treated or Not Treated With Coagulation Factors)
Condition
Hemophilia A
Intervention
Emicizumab
Study Arms / Comparison Groups
Arm A: Emicizumab Prophylaxis at 1.5 mg/kg QW
Description: Participants ≥12 years old with hemophilia A (with or without FVIII inhibitors) who are randomized to Arm A will receive prophylactic emicizumab at a dose of 3 mg/kg via SC injection QW for first 4 weeks, followed by 1.5 mg/kg via SC injection QW for at least 24 weeks. After 24 weeks treatment, participants will be allowed to continue emicizumab until marketing authorization as part of this study or a separate extension study, as long as they derive clinical benefit. Participants will continue to receive standard-of-care treatments on an episodic basis for the treatment of breakthrough bleeds during the study.
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
85
Start Date
April 26, 2018
Completion Date
March 9, 2022
Primary Completion Date
March 9, 2021
Eligibility Criteria
Inclusion Criteria:
Inclusion Criteria for Arms A, B, and C:
- Diagnosis of severe congenital hemophilia A or hemophilia A with FVIII inhibitors
- Aged 12 years or older at the time of informed consent
- Body weight ≥40 kilograms (kg) at the time of screening
- Participants without FVIII inhibitors (<0.6 Bethesda unit per milliliter [BU/mL]) who
completed successful immune tolerance induction (ITI) must have done so at least 5
years before screening and have no evidence of inhibitor recurrence (permanent or
temporary)
- Documentation of the details of episodic therapy (FVIII or bypassing agents) and of
number of bleeding episodes for at least the last 24 weeks and ≥5 bleeds in the last
24 weeks prior to study entry
- Adequate hematologic, hepatic, and renal function
- For women of child bearing potential: agreement to remain abstinent or use a protocol
defined contraceptive measure during the treatment period and for at least 5
elimination half-lives (24 weeks) after the last dose of study drug
Inclusion Criteria for Arm D:
- Diagnosis of congenital hemophilia A of any severity and documented history of
high-titer inhibitor (i.e., ≥5 BU/mL)
- Children <12 years old at time of informed consent
- Body weight >3 kg at time of informed consent
- Requires treatment with bypassing agents
- Adequate hematologic, hepatic, and renal function
- For female participants who are of childbearing potential, follow the same
contraception criteria as listed above for Arms A, B, and C
Exclusion Criteria:
Exclusion Criteria for Arms A, B, and C:
- Inherited or acquired bleeding disorder other than hemophilia A
- At high risk for thrombotic microangiopathy, in the investigator's judgment
- History of illicit drug or alcohol abuse within 48 weeks prior to screening, in the
investigator's judgment
- Previous (in the past 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 that may increase risk of bleeding or thrombosis
- History of clinically significant hypersensitivity associated with monoclonal antibody
therapies or components of the emicizumab injection
- Known human immuno-deficiency virus (HIV) infection with cluster of differentiation 4
(CD4) count <200 cells/microliter (cells/mcL) within 24 weeks prior to screening.
Participants with HIV infection who have CD4 >200 cells/mcL and meet all other
criteria are eligible
- Use of systemic immunomodulators at enrollment or planned use during the study, with
the exception of anti-retroviral therapy
- Concurrent disease, treatment, or abnormality in clinical laboratory tests that could
interfere with the conduct of the study, may pose additional risk, or would, in the
opinion of the investigator, preclude the participant's safe participation in and
completion of the study
- 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 concurrently, within
last 30 days or 5 half-lives, whichever is shorter
- Pregnant or lactating, or intending to become pregnant during the study
Exclusion Criteria for Arm D:
- Inherited or acquired bleeding disorder other than hemophilia A
- Ongoing (or plan to receive during the study) ITI therapy or prophylaxis treatment
with FVIII
- Previous (in the past 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 diseases that may increase risk of bleeding or thrombosis
- History of clinically significant hypersensitivity associated with monoclonal antibody
therapies or components of the emicizumab injection
- Known infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV)
- At high risk for thrombotic microangiopathy, in the investigator's judgment
- Use of systemic immunomodulators at enrollment or planned use during the study
- 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)
- 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 concurrently, within
last 30 days or 5 half-lives, whichever is shorter
- Concurrent disease, treatment, or abnormality in clinical laboratory tests that could
interfere with the conduct of the study, may pose additional risk, or would, in the
opinion of the investigator, preclude the participant's safe participation in and
completion of the study
- Pregnant or lactating, or intending to become pregnant during the study
Gender
All
Ages
N/A - N/A
Accepts Healthy Volunteers
No
Contacts
Clinical Trials, ,
Location Countries
China
Location Countries
China
Administrative Informations
NCT ID
NCT03315455
Organization ID
YO39309
Responsible Party
Sponsor
Study Sponsor
Hoffmann-La Roche
Study Sponsor
Clinical Trials, Study Director, Hoffmann-La Roche
Verification Date
December 2020