E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Haemophilia A is a hereditary bleeding disorder affecting the blood´s ability to clot. Bleeding can occur after injury or spontaneously. |
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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 | 15.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018937 |
E.1.2 | Term | Haemophilia A |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To assess the efficacy of Biostate in paediatric subjects with haemophilia A. • To investigate the PK of Biostate in paediatric subjects with haemophilia A. |
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E.2.2 | Secondary objectives of the trial |
• To assess the safety of Biostate in paediatric subjects with haemophilia A. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male subjects between 0 and <12 years of age. 2. Have been diagnosed with severe haemophilia A (FVIII:C <1%), and pre-treated for a minimum of 20 to 50 exposure days. 3. Have evidence of vaccination against hepatitis A and B (or presence of antibodies against hepatitis A and B due to either a previous infection or prior immunisation), as documented in the medical notes at enrolment. Children < 1 year of age may be included in the study without evidence of vaccination against hepatitis A. 4. The subject and/or legal guardian understand(s) the nature of the study and has/have given written informed consent to participate in the study and is/are willing to comply with the protocol. |
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E.4 | Principal exclusion criteria |
1. For all subjects at Day 1:Are actively bleeding. 2. Have received an infusion of any FVIII product, cryoprecipitate, whole blood, plasma or desmopressin acetate in the 4 days prior to their dosing within the PK component. 3. Have a known history of, or who are suspected of having FVIII inhibitors. 4. Have received aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) within 7 days of administration of the IMP. 5. Have an impaired liver function ie, bilirubin >1.5 x upper limit of normal (ULN) and/or aspartate/alanine aminotransferase (AST/ALT) >2.5 x ULN (referring to limits of the laboratory that performs the determination) at Screening. 6. Are human immunodeficiency virus [HIV]-1/-2 antibody positive with a viral load of >200/µL. 7. Suffer from an acute or chronic medical condition, other than haemophilia A, which may, in the opinion of the Investigator, affect the conduct of the study. 8. Suffering from von Willebrand disease (VWD) with von Willebrand factor: ristocetin cofactor (VWF:RCo) level <50 IU/dL at Screening. 9. Have a known or suspected hypersensitivity or previous evidence of severe side effects to a plasma-derived FVIII product or to human albumin. 10. Have participated in a clinical study or used an investigational compound in another study (eg, a new chemical entity not registered for clinical use) in the 3 months preceding the first day of IMP administration, or are planning to enter such a study during the study period. 11. Unwillingness and/or inability to comply with the study requirements. |
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E.5 End points |
E.5.1 | Primary end point(s) |
a) Subjective assessment of haemostatic efficacy of Biostate, the investigational medicinal product (IMP), in its usage over a minimum of 50 exposure days. b) PK parameters for factor VIII (FVIII) will be derived from plasma concentration values collected after an initial single dose of Biostate on Day 1. c) FVIII concentrate usage: number of infusions, International units (IU)/kg per event, month, year. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
a) Monthly basis b) PK parameters in plasma 0.5, 4, 8, 24 and 48 hours after administration. c) Data collected on an on-going basis per patient: evaluation at IDMC meetings, close of study |
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E.5.2 | Secondary end point(s) |
a) The nature and incidence of AEs. b) The development of FVIII inhibitors.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
a) IDMC meetings and at close of study b) Screening, Day 2, 1 month, 3 month and final 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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Prophylaxis treatment in selected patients - clinical benefit |
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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 | Information not present in EudraCT |
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) | 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.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 |
Belarus |
Georgia |
Guatemala |
Lebanon |
Mexico |
Ukraine |
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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
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The day of the last visit of the last subject enrolled in the study |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |