E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe Hemophilia-A (< 1% FVIII:C) |
Severe Hemophilia-A (< 1% FVIII:C) |
|
E.1.1.1 | Medical condition in easily understood language |
Hemophilia A is X-linked congential bleeding disorder causing frequent bleedings and recurrent spontanious bleeds into the soft tissue and joints, leading to joint damage and severe disability. |
Hemophilia A is X-linked congential bleeding disorder causing frequent bleedings and recurrent spontanious bleeds into the soft tissue and joints, leading to joint damage and severe disability. |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060612 |
E.1.2 | Term | Hemophilia A |
E.1.2 | System Organ Class | 100000004850 |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to evaluate the safety and efficacy of the treatment with
BAY 81-8973 for prophylaxis and treatment of breakthrough bleeds in children with haemophilia A |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives are
- To assess the safety and efficacy of BAY 81-8973 during surgeries.
- To assess incremental recovery of BAY 81-8973.
- To assess pharmacokinetic parameters in a subset of children. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Part A
1. Male, age ≤ 12 years. Enrollment will begin with subjects 6-12
years before it is opened to all age groups.
2. Severe hemophilia A defined as < 1% factor VIII concentration
(FVIII:C) based on documented prior testing or screening
laboratory
3. >/= 50 ED with any FVIII concentrate
4. No current evidence of inhibitor antibody measured using the
Nijmegen modified Bethesda assay [<0.6 Bethesda units (BU)/mL]
within 2-3 weeks of last FVIII administration.
5. No history of FVIII inhibitor formation. Documentation of negative
result in medical records required. [Subjects with a maximum historical
titer of 1.0 BU on no more than 1 occasion with the classical Bethesda
assay but at least 3 successive negative (<0.6 BU) results thereafter are
eligible.]
6. Willingness and ability of subjects and/or parents to complete
training in the use of the electronic patient diary (EPD) and to document
infusions during the study.
7. Written informed consent by parent/legal representative. Assent
should be sought from subjects if appropriate
Part B (PUPs)
1. Male, < 6 years and under
2. Severe hemophilia A defined as < 1% FVIII:C based on prior
documented testing or confirmed on screening laboratory
3. No previous exposure to any FVIII product
4. PUPs may be included if they will receive their first FVIII dose with
BAY 81-8973 for treatment of first bleeds and agree to start prophylaxis
as part of their care.
5. Willingness and ability of parents to complete training in the use of
the electronic patient diary (EPD) and to document all treatment during
the study.
6. Written informed consent by parent/legal representative. |
|
E.4 | Principal exclusion criteria |
Parts A and B
1. Any individual with another bleeding disorder that is different from
Hemophilia A (eg, von Willebrand disease, Hemophilia B)
2. Any individual with thrombocytopenia (platelet count <
100,000/mm3)
3. Creatinine > 2x upper limit of normal or AST/ALT > 5x upper limit of
normal
4. Any individual without a negative inhibitor at screening (except for PUPs)
5. Any individual who is receiving chemotherapy, immune modulatory
drugs (IVIG, cyclosporine, chronic use of oral or i.v. corticosteroids), has
received anotherinvestigational FVIII product withinthe last month, or received another experimental drug within the last 3 months.
6. Any individual who requires any pre-medication to tolerate FVIII
treatment (eg, antihistamines).
7. Any individual who is unwilling to comply with study visits or other
protocol requirements, for example (eg. prophylaxis treatment) or is not
suitable for participation in this study for any reason, according to the
Investigator's judgment.
8. Known hypersensitivity to active substance, mouse or hamster
protein.
9. Previous participation in this study
Part B only (PUPs):
10. First treatment with BAY 81-8973 for high risk bleeding situations
(e.g. surgery, intracranial bleed), or requiring intensive or prolonged
treatment.
11. Unable to tolerate volume of blood draws required for study
participation.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary variable is the annualized number of total bleeds (sum of
spontaneous bleeds and traumatic bleeds) during prophylaxis that occur
within 48 h of the last prophylaxis infusion. Both joint and non-joint
bleeding will be assessed. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Continuous throughout duration of study |
|
E.5.2 | Secondary end point(s) |
•Subject/parents' assessment of the response of treatment of bleeding
events which is assessed as excellent, good, moderately well or poorly.
•Annualized number of total bleeds (sum of spontaneous and trauma
bleeds) during prophylaxis treatment
•Assessment of adequacy of haemostasis during surgical interventions
•Number of infusions for the treatment of a bleed
•Consumption of FVIII |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Continuous throughout duration of study |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Canada |
Denmark |
Hungary |
Ireland |
Israel |
Italy |
Latvia |
Lithuania |
Poland |
Romania |
Serbia |
Sweden |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
End of the trial is the last visit (follow-up phone call 1-2 weeks after
end of treatment) of the last subject undergoing study. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 3 |