The study will investigate the safety and efficacy of emicizumab in patients with hemophilia A with inhibitors against FVIII.
ID
Source
Brief title
Condition
- Blood and lymphatic system disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of this study is to evaluate the overall safety and
tolerability of prophylactic administration of emicizumab in patients with
hemophilia A. The specific focus will be to characterize any thromboembolic
events, microangiopathic hemolytic anemia, thrombotic microangiopathy (TMA)
(e.g. hemolytic uremic syndrome), and hypersensitivity reactions that may occur
in patients with hemophilia A treated with emicizumab.
Secondary outcome
The secondary objective of this study is to evaluate the efficacy of
prophylactic administration of emicizumab. As part of this objective, the
number of bleeds over time will be recorded for all of the enrolled patients.
Background summary
Hemophilia A is a rare bleeding disorder that is attributable to a congenital
absence or hypofunctioning of Factor VIII (FVIII). The gene that encodes FVIII
is located on the X chromosome. Genetic defects are expressed through X-linked
recessive inheritance or de novo FVIII mutations, and more than 99% of
hemophilia patients are males.
The absence or functional deficiency of FVIII leads to a lifelong bleeding
tendency. Common clinical signs of hemophilia A include easy bruising;
prolonged bleeding after trauma or surgery; spontaneous bleeding into joints,
muscles, or soft tissues; and intracranial hemorrhage.
For patients with hemophilia A who are diagnosed with inhibitors, permanent
eradication of these inhibitors is currently the ultimate aim of therapy. This
can be achieved by means of intensive FVIII administration over many months
with immune tolerance induction (ITI), and for those patients with inhibitors
who are unable to eradicate their inhibitors or are not candidates for ITI,
bypassing agents are required to treat or prevent bleeds.
Given the hemostatic management challenges with the current treatment options
in adults and children with inhibitors, there is a clinical need for
therapeutics that have a lower treatment burden, more reliable efficacy, and an
extended t1/2 that can be used for preventing bleeding in patients with
hemophilia A.
Study objective
The study will investigate the safety and efficacy of emicizumab in patients
with hemophilia A with inhibitors against FVIII.
Study design
Single-arm, multicenter, open label Phase IIIb clinical study
Intervention
Patients will receive treatment with emicizumab during this study. Emicizumab
is administered through the use of an injection just beneath the surface of the
skin. You will receive one dose of emicizumab every week. You will initially
receive a dose of 3 mg per kilogram of body weight (so a 70 kg person would
receive 210 mg of emicizumab), for a total of 4 doses. After 4 weeks, your dose
will be halved to 1.5 mg per kilogram of body weight (a 70 kg person would
receive 105 mg of emicizumab). You will then receive the same dose of
emicizumab every week for the rest of the 2-year treatment period, unless you
are told otherwise by your doctor.
Study burden and risks
Emicizumab is not approved, and clinical development is ongoing. Thus, the
complete safety profile is not known at this time. The safety plan for patients
in this study is based on clinical experience with emicizumab in completed and
ongoing studies. The anticipated important safety risks for emicizumab are
outlined in protocol section 5.1. Please refer to the emicizumab Investigator's
Brochure for a complete summary of safety information.
Beneluxlaan 2a
Woerden 3446 GR
NL
Beneluxlaan 2a
Woerden 3446 GR
NL
Listed location countries
Age
Inclusion criteria
- As per the investigator's judgment, 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
- Body weight ><=40 kg at the time of screening
- 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/*L 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
*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)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-004366-25-NL |
| CCMO | NL61146.041.17 |