| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| severe hemophilia A (<1% FVIII:C) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Hemophilia A is an X-linked congenital bleeding disorder causing frequent bleedings and recurrent spontaneous bleeds into the soft tissue and joints, leading to joint damage and severe disability. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10060612 |
| E.1.2 | Term | Hemophilia A |
| E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.0 |
| E.1.2 | Level | SOC |
| E.1.2 | Classification code | 10010331 |
| E.1.2 | Term | Congenital, familial and genetic disorders |
| E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
| 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 |
To evaluate pharmacokinetics, safety, and efficacy of BAY 94-9027 for prophylaxis and treatment of bleeding in previously treated patients with
hemophilia A |
|
| E.2.2 | Secondary objectives of the trial |
Primary endpoints:
- Number of bleeding events during prophylactic treatment
- Assessment of PK, including Cmax, incremental recovery, MRT, Apparent volume of
distribution at steady state (Vss), half-life, area under the curve (AUC), and clearance, in
at least 12 subjects in each age subgroup, with at least 4 pre-selected time points
between pre-dose and 72 h post-infusion.
- Response of acute bleeding events to treatment will be rated using a 4-point scale
(poor, moderate, good, or excellent) by the subject/parent or by the treating physician
if the subject is hospitalized
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male, age <12 years to be enrolled in 2 subgroups:
- age 6 to <12 years
- age < 6 years
2. Severe hemophilia A defined as < 1% factor VIII concentration (FVIII:C) by measurement at the time of screening or from reliable prior documentation (eg, measurement in other clinical trials, results from approved clinical laboratory, or
diagnostic genetic testing)
3. > 50 ED with any FVIII concentrate(s) (plasma derived or recombinant)
4. Willingness and ability of subjects and/or parents to complete training in the use of the
EPD and to document infusions during the study
5. Written informed consent by parent/legal representative. Assent should be sought from
subjects, if appropriate |
|
| E.4 | Principal exclusion criteria |
1. Current evidence of inhibitor to FVIII measured using the Nijmegen-modified Bethesda assay (>0.6 BU/mL) at the time of screening (central laboratory). Subjects should not have received FVIII within 72 h prior to the collection of screening
samples and should have had FVIII administered within the prior 2-3 weeks.
2. History or presence of Factor VIII inhibitors. Inhibitor to FVIII is defined as a titer
>0.6 BU/mL or clinical history suggestive of inhibitor requiring modification of treatment. (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 subsequent negative results [<0.6 BU] are eligible.)
3. Any other inherited or acquired bleeding disorder in addition to hemophilia A
4. Platelet count < 100,000/mm3
5. Creatinine > 2x upper limit of normal
6. Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) > 5x upper
limit of normal
7. Known hypersensitivity to the drug substance, or any of its components (eg, mouse or
hamster protein)
8. 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 may continue treatment with the product
up to the start of Visit 1.
9. Any individual who is receiving chemotherapy, immune modulatory drugs other than anti-retroviral chemotherapy, or chronic use of oral or intravenous (IV) corticosteroids (> 14 days) within the last 3 months.
10. The subject is identified by the investigator as being unable or unwilling to perform study procedures.
11. Previous assignment to treatment during this study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary endpoints:
- Number of bleeding events during prophylactic treatment
- Assessment of PK, including Cmax, incremental recovery, MRT, Apparent volume of
distribution at steady state (Vss), half-life, area under the curve (AUC), and clearance, in
at least 12 subjects in each age subgroup, with at least 4 pre-selected time points
between pre-dose and 72 h post-infusion.
- Response of acute bleeding events to treatment will be rated using a 4-point scale
(poor, moderate, good, or excellent) by the subject/parent or by the treating physician
if the subject is hospitalized
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Number of bleedings: at the end of treatment visit
- Assessment of PK values: at the PK visit
- Response to treatment of acute bleedings: end of treatment visit
|
|
| E.5.2 | Secondary end point(s) |
- Inhibitor development after 10-15 and 50 ED
- Assess incremental recovery in all subjects
- Safety and tolerability assessments |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Inhibitor development: after 10-15 and after 50 ED of each subject
- Safety and tolerability assessments: at the end of treatment visit and FU visit
|
|
| 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 | No |
| 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 | Yes |
| 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) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| 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 | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 21 |
| 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 | No |
| 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 |
| Argentina |
| Canada |
| European Union |
| Israel |
| 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 | 2 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
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