Brief Title
A Study to Evaluate the Safety and Tolerability of Prophylactic Emicizumab in Hemophilia A Patients With Inhibitors
Official Title
A Single-Arm, Multicenter Phase IIIB Clinical Trial to Evaluate the Safety and Tolerability of Prophylactic Emicizumab in Hemophilia A Patients With Inhibitors
Brief Summary
This is a phase IIIb, single arm, open-label, multi-center study to evaluate the safety and
tolerability of emicizumab in participants with congenital hemophilia A who have documented
inhibitors against Factor VIII (FVIII) at enrollment. Approximately 200 participants, aged 12
or older, will be enrolled in this study and are expected to be enrolled at approximately 85
sites globally. Participants will receive an initial weekly dose of prophylactic emicizumab
subcutaneously for 4 weeks, followed by a weekly maintenance dose subcutaneously for the
remainder of the 2-year treatment period.
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Incidence and severity of all adverse events (AEs) including thromboembolic events, microangiopathic hemolytic anemia or TMA (e.g. hemolytic uremic syndrome), systemic hypersensitivity, anaphylaxis, and anaphylactoid events
Secondary Outcome
Numbers of bleeds over time
Condition
Hemophilia A
Intervention
Emicizumab
Study Arms / Comparison Groups
Emicizumab
Description: Participants will receive initial weekly doses of prophylactic emicizumab subcutaneously for 4 weeks, followed by maintenance doses consisting of half the initial dose, administered subcutaneously for the remainder of the 2-year treatment period
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
195
Start Date
September 5, 2017
Completion Date
November 19, 2020
Primary Completion Date
November 19, 2020
Eligibility Criteria
Inclusion Criteria:
- As per investigator's judgement, a willingness and ability to comply with scheduled
visits, treatment plans, laboratory tests, and other study procedures, including the
patient-reported outcome (PRO) questionnaires and bleed diaries through the use of an
electronic device or paper
- Aged 12 years or older at the time of informed consent
- Diagnosis of congenital hemophilia A with persistent inhibitors against FVIII
- Documented treatment with bypassing agents or FVIII concentrates in the last 6 months
(on-demand or prophylaxis). Prophylaxis needs to be discontinued the latest by a day
before starting emicizumab
- Adequate hematologic, hepatic, and renal function
- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use a highly effective contraceptive method with a
failure rate of <1% per year during the treatment period and for at least five
elimination half-lives (24 weeks) after the last dose of emicizumab
Exclusion Criteria:
- Inherited or acquired bleeding disorder other than hemophilia A
- Ongoing (or plan to receive during the study) immune tolerance induction (ITI) therapy
(prophylaxis regimens with FVIII and/or bypassing agents must be discontinued prior to
enrollment). Patients receiving ITI therapy will be eligible following the completion
of a 72-hour washout period prior to the first emicizumab administration
- History of illicit drug or alcohol abuse within 12 months prior to screening, as per
the investigator's judgment
- High risk for thrombotic microangiopathy (TMA) (e.g., have a previous medical or
family history of TMA), as per 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 antithrombotic
treatment is not currently ongoing) or current signs of thromboembolic disease
- Other conditions (e.g., certain autoimmune diseases) that may increase the risk of
bleeding or thrombosis
- History of clinically significant hypersensitivity reaction associated with monoclonal
antibody therapies or components of the emicizumab injection
- Known human immunodeficiency virus (HIV) infection with CD4 count <200 cells/μL within
6 months prior to screening
- Use of systemic immunomodulators (e.g., interferon or rituximab) at enrollment or
planned use during the study, with the exception of antiretroviral therapy
- 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 patient's safe participation in and completion
of the study or interpretation of the study results
- Receipt of: Emicizumab in a prior investigational study; An investigational drug to
treat or reduce the risk of hemophilic bleeds within five half-lives of last drug
administration; A non-hemophilia-related investigational drug within last 30 days or
five half-lives, whichever is shorter; or, Any concurrent investigational drug.
- Pregnancy or lactation, or intent to become pregnant during the study
- Positive serum pregnancy test result within 7 days prior to initiation of emicizumab
(females only)
Gender
All
Ages
12 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Clinical Trials, ,
Location Countries
Australia
Location Countries
Australia
Administrative Informations
NCT ID
NCT03191799
Organization ID
MO39129
Secondary IDs
2016-004366-25
Responsible Party
Sponsor
Study Sponsor
Hoffmann-La Roche
Study Sponsor
Clinical Trials, Study Director, Hoffmann-La Roche
Verification Date
December 2020