PART A: To assess the efficacy of BAY 94-9027 in prevention and treatment of bleeding at different infusion schedules.PART B: To assess the safety and efficacy of BAY 94-9027 in the prevention of bleeding during major surgical procedures.
ID
Source
Brief title
Condition
- Coagulopathies and bleeding diatheses (excl thrombocytopenic)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Total number of bleedings as reported by the subjects (efficacy)
Secondary outcome
- questionnaires (evaluate subject*s assessment)
- adverse events (safety and tolerability)
- pharmacokinetics and incremental recovery following administration of Bay
94-9027
- questionnaires for quality of life, work productivity and pain
Background summary
BAY 94-9027 could provide a clinical benefit in subjects with severe hemophilia
A in preventing bleeds. This could decrease the number of infusions with
FVIII.
See protocol page 16-19
Study objective
PART A: To assess the efficacy of BAY 94-9027 in prevention and treatment of
bleeding at different infusion schedules.
PART B: To assess the safety and efficacy of BAY 94-9027 in the prevention of
bleeding during major surgical procedures.
Study design
Design PART A: The study consists of an up to 36-week treatment period.
On-demand treatment arm: subjects will receive BAY 94-9027 for on demand
treatment of acute bleeding events for 36 weeks.
Prophylactic treatment arm: subjects receive regularly scheduled infusion as
per treatment arm assignment. All subjects entering the prophylaxis arm will
start with 2x/week infusion. Following a clinical assessment at Week 10, a
subset of subjects will continue in the 2x/week treatment arm for an additional
26 weeks. All others will be randomized 1:1 to either an every 5 days or every
7 days prophylactic infusion for an additional 26 weeks.
For all subjects, infusions and bleeding events will be documented in an
electronic subject diary (ePD) throughout the study.
The subjects* health, quality of life, measurements of in vivo recovery, and
any inhibitor or antibody development will be assessed at specific intervals.
Design PART B:
Part B is open to all subjects participating in Part A and to individuals with
severe hemophilia A, requiring a major surgery, not otherwise enrolled in this
clinical study who meet the same inclusion and exclusion criteria as required
in Part A. Subjects may participate in Part B more than once.
Intervention
There will be 4 treatment arms:
- An on-demand group
- Twice a week
- Once every 5 days
- Once a week
The trial can be divided in the following phases:
- Screening phase (for all patients)
- patients in the on-demand group
- All subjects entering the prophylaxis arm will start with 2x/week infusion.
Subjects in prophylactic treatment arms will undergo clinical evaluation at 10
weeks. Those with adequate control of bleeding will undergo randomization to
every 5 or 7 day infusion. Those with continued bleeding will remain in
treatment arm and have an increase in dose.
The total duration of the treatment is 36 weeks.
Extension study:
The purpose of the extension phase is to provide further observations on the
safety and efficacy of BAY 94-0927. It is asked that all subjects participating
remain in the extension until they have accumulated at least 100 total days of
treatment (including the treatments received in the main study). If you decide
to participate in the study, you will be asked to continue treatment until you
have received 100 total days of treatment with BAY 94-9027. This may take
between at least 6 to12 months depending upon your frequency of infusion or how
often you have bleeds. If you have already or will soon have 100 days, you may
be in the extension for at least 6 months, and for as long as it is running.
Study burden and risks
- 10 hospital visits
- Physical examination (3x)
- Hart rate, blood pressure (6x)
- Joint assessment (Gilbert-score) (1x)
- Weight(5x)
- ECG (1x)
- Lab (7x)
- Questionnaires at three visits
- Possible adverse events
Energieweg 1
Mijdrecht 3641 RT
NL
Energieweg 1
Mijdrecht 3641 RT
NL
Listed location countries
Age
Inclusion criteria
* Male; 12 to 65 years of age (or Male 18-65 years of age in countries where enrollment of minors is not permitted)
* Subjects with severe hemophilia A (baseline FVIII activity FVIII:C <1%) determined by measurement at the time of screening or from reliable prior documentation (eg, measurement in other clinical trials, result from approved clinical laboratory)
* Previously treated with FVIII concentrate(s) (plasma derived or recombinant) for a minimum of 150 ED
* Immunocompetent. If HIV positive, CD4+ lymphocyte count >200/mm3
Exclusion criteria
* Current evidence of inhibitor to FVIII with a titer * 0.6 BU/mL, measured by the Nijmegen modified Bethesda assay at the time of screening (central laboratory) (BU: Bethesda unit)
* History of inhibitor to FVIII with a titer * 0.6 BU, or clinical history suggestive of inhibitor requiring modification of treatment. Subjects with a maximum historical titer of 1.0 BU on a single measurement but with at least 3 subsequent successive negative results (< 0.6 BU) thereafter are eligible
* Any other inherited or acquired bleeding disorder in addition to Hemophilia A
* Platelet count < 100,000/mm3
* Creatinine > 2x upper limit of normal
* AST or ALT > 5x upper limit of normal (AST: aspartate aminotransferase; ALT: alanine aminotransferase)
* The subject is currently participating in another investigational drug study, or has participated in a clinical study involving an investigational drug within 30 days of study entry. Subjects who are currently participating in an investigational study in which they are treated with a currently marketed FVIII concentrate are not excluded. Subjects currently treated with BAY 81-8973, and who have received at least 100 ED with the investigational product, may continue treatment with the product up to the start of Visit 1.
* Any subject who is receiving chemotherapy, immune modulatory drugs other than anti-retroviral chemotherapy, or chronic use of oral or intravenous (IV) corticosteroids within the last 3 months. Brief courses of prednisone/methyprednisolone (< 14 days) for treatment of disorders such as synovitis, asthma, etc are allowed at the discretion of the treating physician.
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 | EUCTR2011-005210-11-NL |
| ClinicalTrials.gov | NCT01580293 |
| CCMO | NL40664.042.12 |