E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe hemophilia A (<1% FVIII:C) |
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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. |
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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 | 20.0 |
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 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
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 |
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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 assess the safety and tolerability of BAY94-9027 replacement therapy in previously treated patients 7 to < 12 years of age with severe hemophilia A |
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E.2.2 | Secondary objectives of the trial |
To describe the clinical efficacy of BAY94-9027 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Participant must be 7 to <12 years of age at the time of parent / guardian signing the informed consent. 2. Participants with known medical history of severe hemophilia A (participant’s own FVIII activity [FVIII:C] <1%. FVIII:C) based on reliable prior documentation in clinical records of the participants. If no reliable documentation is available, FVIII activity must be measured at the time of screening after a 48-72 hours wash-out period (depending on his previous product). 3. Male 4. Participants must be previously treated with FVIII concentrate(s) (plasma derived or recombinant) for a minimum of 50 exposure days (EDs) at the time of signing the informed consent. 5. Participant has understood the study and if appropriate for his age, has signed an informed assent. The parent(s) or guardian(s) is capable of giving signed informed consent and are able to comply with the requirements and restrictions listed in the informed consent form (ICF) and the protocol. 6. Willingness and ability of participants and/or parents /caregivers to complete training in the use of the electronic patient diary (EPD) and to document infusions during the study.
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E.4 | Principal exclusion criteria |
1. History of FVIII inhibitors. Inhibitor to FVIII is defined as a titer >0.6 BU/mL or clinical history suggestive of inhibitor requiring modification of treatment. Participants 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. 2. Current evidence of inhibitor to FVIII measured using the Nijmegen modified Bethesda assay (>0.6 BU/mL) at the time of screening (central laboratory). Participants should not receive FVIII within 48 h prior to the collection of screening samples and should have FVIII administered within the prior 2-3 weeks 3. Any other inherited or acquired bleeding disorder in addition to hemophilia A (e.g., von Willebrand disease, hemophilia B) 4. Platelet count <100,000 cells/µL 5. Serum creatinine > 2x upper limit of normal 6. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5x upper limit of normal 7. Known hypersensitivity or allergic reaction to drug substance, excipients or mouse or hamster protein 8. Any other significant medical condition that the investigator feels would be a risk to the participant or would impede the study 9. Requires any pre-medication to tolerate FVIII treatment (e.g. antihistamines) 10. Planned major surgery during the study 11. Any individual who is currently receiving or received 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 12. Any individual who received commercially available subcutaneous factor substitution therapy (emicizumab) within the last 6 months 13. The participant 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 or previous participation in a clinical study with BAY 94-9027. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• AESI (hypersensitivity and LODE*) associated with the first 4 EDs leading to discontinuation
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
AESI within the first 4 exposure (dose) days; the first two weeks
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E.5.2 | Secondary end point(s) |
Secondary endpoints • Adverse drug reactions (ADRs) • Anti-drug antibody (ADA) development • Inhibitor development • Annualized bleeding rate (ABR) • BAY 94-9027 consumption • Number of infusions/month and year (Annualized Infusion Rate)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All secondary endpoints from time of first dose to last study visit |
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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 | No |
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.8.3 |
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 | 3 |
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 |
Brazil |
Canada |
United States |
Italy |
Norway |
Turkey |
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E.8.7 | Trial has a data monitoring committee | No |
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
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The end of the trial is the last visit (follow-up call 2 weeks after end of treatment) of the last subject undergoing study treatment |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |