A Multicenter, Open-Label Study to Evaluate the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Emicizumab in Patients with Mild or Moderate Hemophilia A without FVIII Inhibitors
- Conditions
- Bleeding disorderHemophilia A10064477
- Registration Number
- NL-OMON48013
- Lead Sponsor
- Roche Nederland B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 3
• Signed Informed Consent Form (signed by patient*s legally authorized
representative for patients who have not attained the age of majority)
• Signed Assent Form when appropriate, as determined by patient's age and
individual site and country standards
• Willingness and ability to comply with schedules visits, treatment plans,
laboratory tests and other study procedures
• Diagnosis of mild (FVIII level between >5% and <40%) or moderate (FVIII level
between >= 1% and <= 5%) congenital Hemophilia A without FVIII inhibitors
• Weight >= 3 kg
• Need for prophylaxis based on investigator assessment
• A negative test for inhibitor (i.e., < 0.6 BU/mL) within 8 weeks prior to
enrollment
• No documented inhibitor (i.e., < 0.6 BU/mL), FVIII half-life < 6 hours, or
FVIII recovery < 66% in the last 5 years
• Patients who completed successful immune tolerance induction (ITI) at least 5
years before screening are eligible, provided they have had no evidence of
inhibitor recurrence (permanent or temporary) as may be indicated by a
detection of an inhibitor, FVIII half-life <6 hours or FVIII recovery <66%
since completing ITI.
• Documentation of the details of prophylactic or episodic FVIII treatment and
of number of bleeding episodes for at least the last 24 weeks prior to
enrollment
• Adequate hematologic function, defined as platelet count >= 100,000 cells/µL
and hemoglobin >= 8 g/dL (4.97 mmol/L) at the time of screening
• Adequate hepatic function defined as total bilirubin <= 1.5 X age-adapted
upper limit of normal (ULN) (excluding Gilbert syndrome) and both AST and ALT <=
3 x age-adapted ULN at the time of screening, and no clinical signs or known
laboratory/radiographic evidence consistent with cirrhosis
• Adequate renal function, defined as serum creatinine <= 2.5x age-adapted ULN
and creatinine clearance >= 30 mL/min by Cockroft-Gault formula
• For women of childbearing potential: agreement to remain abstinent (refrain
from heterosexual intercourse) or use contraception as defined in section 4.1.1
of the Clinical Protocol
• Inherited or acquired bleeding disorder other than mild (FVIII level between
> 5% and < 40%) or moderate (FVIII level between >= 1% and <= 5%) congenital
hemophilia A
• History of illicit drug or alcohol abuse within 48 weeks prior to screening,
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 (e.g., 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
• Planned surgery during the emicizumab loading dose phase (surgeries in
patients on emicizumab from Week 5 onwards are allowed)
• Known HIV infection with CD4 counts < 200 cells/µL
• Concomitant disease, condition, significant abnormality on screening
evaluation 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 patient
• Receipt of any of the following
o An investigational drug to treat or reduce the risk of hemophilic bleeds
within 5 half-lives of last drug administration with the exception of prior
emicizumab prophylaxis (prior investigational or commercial emicizumab use is
not an exclusion criterion)
o A non-hemophilia-related investigational drug within last 30 days or 5
half-lives, whichever is shorter
o Any other investigational drug currently being administered or planned to be
administered
• Inability to comply with the study protocol in the opinion of the investigator
• Pregnant or breastfeeding, or intending to become pregnant during the study
(women of childbearing potential must have a negative serum pregnancy test
result within 7 days prior to initiation of study drug)
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Safety endpoints:<br /><br>• Incidence and severity of adverse events, with severity determined according<br /><br>to WHO Toxicity Grading Scale<br /><br>• Incidence of thromboembolic events<br /><br>• Incidence of thrombotic microangiopathy (TMA)<br /><br>• Change from baseline in physical examination findings<br /><br>• Change from baseline in and vital signs<br /><br>• Change from baseline in ECG parameters<br /><br>• Incidence of laboratory abnormalities<br /><br>• Incidence and severity of injection-site reactions<br /><br>• Incidence of adverse events leading to drug discontinuation<br /><br>• Incidence of severe hypersensitivity, anaphylaxis, and anaphylactoid events<br /><br>• Incidence and significance of anti-emicizumab antibodies<br /><br>• Incidence of de novo development of FVIII inhibitors<br /><br><br /><br>Efficacy endpoints:<br /><br>• Number of treated bleeds over time (i.e., bleed rate)</p><br>
- Secondary Outcome Measures
Name Time Method