A PHASE IIIb, MULTICENTER, OPEN-LABEL, SINGLE-ARM STUDY TO EVALUATE THE EFFICACY, SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF SUBCUTANEOUS EMICIZUMAB IN PATIENTS FROM BIRTH TO 12 MONTHS OF AGE WITH HEMOPHILIA A WITHOUT INHIBITORS
- Conditions
- Hemophilia A10064477
- Registration Number
- NL-OMON51172
- Lead Sponsor
- Roche Nederland B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 2
* Age from birth to <<= 12 months at time of informed consent
* Body weight ><= 3 kg at time of informed consent
* Mandatory receipt of vitamin K prophylaxis according to local standard
practice
* Diagnosis of severe congenital hemophilia A (intrinsic FVIII level < 1%)
* A negative test for FVIII inhibitor (i.e., < 0.6 Bethesda units [BU]/mL)
locally assessed during the 2-week screening period for all patients
* For PUPs or MTPs, up to 5 days of exposure with hemophilia-related
treatments, such as plasma-derived FVIII, recombinant FVIII, fresh frozen
plasma, cryoprecipitate, or whole blood products
* Documentation of the details of the hemophilia-related treatments received
since birth
* Documentation of the details of the bleeding episodes since birth
* For patients from birth to < 3 months of age at the time of study entry: no
evidence of active ICH, as confirmed by a negative cranial ultrasound at
screening irrespective of delivery mode
* Adequate hematologic, hepatic, and renal function
Exclusion criteria
* Inherited or acquired bleeding disorder other than severe hemophilia A
* Use of systemic immunomodulators (e.g., interferon) at enrollment or planned
use during the study
* Receipt of any of the following:
* An investigational drug to treat or reduce the risk of hemophilic bleeds
within 5 drug-elimination half-lives of last drug administration
* A non-hemophilia-related investigational drug within the last 30 days or 5
drug-elimination half-lives, whichever is shorter
* An investigational drug concurrently
* Current active severe bleed, such as ICH
* Planned surgery during the study
* History of clinically significant hypersensitivity associated with monoclonal
antibody therapies or components of the emicizumab injection
* Previous or current treatment for thromboembolic disease or signs of
thromboembolic disease
* Any hereditary or acquired maternal condition that may predispose the patient
to thrombotic events
* Other diseases (e.g., certain autoimmune diseases) that may increase risk of
bleeding or thrombosis
* Known infection with HIV, hepatitis B virus, or hepatitis C virus
* Serious infection requiring antibiotics or antiviral treatments within 14
days prior to screening
* Concurrent disease, treatment, abnormality in clinical laboratory tests,
vital signs measurements, or physical examination findings 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
* Unwillingness of the parent or caregiver to allow receipt of blood or blood
products, or any standard-of-care treatment for a life-threatening condition
* Any other medical, social, or other condition that may prevent adequate
compliance with the study protocol in the opinion of the investigator
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The efficacy objective for this study is to evaluate the efficacy of emicizumab<br /><br>on the basis of the following endpoints:<br /><br>- Number of treated bleeds over time (i.e., treated bleed rate)<br /><br>- Number of all bleeds over time (i.e., all bleed rate)<br /><br>- Number of treated spontaneous bleeds over time (i.e., treated spontaneous<br /><br>bleed rate)<br /><br>- Number of treated joint bleeds over time (i.e., treated joint bleed rate)<br /><br>- Joint health, as assessed through use of the Hemophilia Joint Health Score<br /><br>(HJHS) and magnetic resonance imaging (MRI) score of specific joints at<br /><br>specified timepoints only during the 7-year LTFU period</p><br>
- Secondary Outcome Measures
Name Time Method <p>The safety objective for this study is to evaluate the safety of emicizumab on<br /><br>the basis of the following endpoints:<br /><br>- Incidence and severity of adverse events, with severity determined according<br /><br>to<br /><br>WHO Toxicity Grading Scale (see Appendix 5)<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 vital signs<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><br /><br>See protocol section 2 for Pharmacokinetic, biomarker and Immunogenicity<br /><br>objectives</p><br>