E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with hemophilia A or B with inhibitors |
Soggetti affetti da emofilia A o B con inibitori. |
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E.1.1.1 | Medical condition in easily understood language |
Subjects with hemophilia A or B with inhibitors |
Soggetti affetti da emofilia A o B con inibitori. |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053751 |
E.1.2 | Term | Hemophilia A with anti factor VIII |
E.1.2 | System Organ Class | 100000004850 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053752 |
E.1.2 | Term | Hemophilia B with anti factor IX |
E.1.2 | System Organ Class | 100000004850 |
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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 |
Part A:
- To identify the recommended dose by conducting a risk-benefit assessment of four different dose levels of BAY 86-6150 based on safety and dose response assessments in acutely bleeding subjects with hemophilia A or B with inhibitors.
Part B:
- To further investigate the safety and efficacy of the recommended dose of BAY 86-6150 in acutely bleeding subjects with hemophilia A or B with inhibitors. |
Parte A:
•Identificare la dose raccomandata attraverso una valutazione del rapporto rischio/beneficio di quattro diversi dosaggi di BAY 86-6150, sulla base di valutazioni di sicurezza e di risposta alla dose in soggetti con emorragia acuta affetti da emofilia A o B con inibitori.
Parte B:
•Esaminare ulteriormente la sicurezza e l’efficacia della dose raccomandata di BAY 86-6150 in soggetti con emorragia acuta affetti da emofilia A o B con inibitori.
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E.2.2 | Secondary objectives of the trial |
- To assess the potential immunogenicity of BAY 86-6150 in subjects with hemophilia A or B with inhibitors.
- To evaluate the comparative PK/PD (pharmacokinetics/pharmacodynamics) parameters to one fixed dose of eptacog alfa (activated) in a subset of the above cohorts at the same four dose levels of BAY 86-6150. |
Obiettivi secondari:
•Valutare la potenziale immunogenicità di BAY 86-6150 in soggetti affetti da emofilia A o B con inibitori.
•Confrontare i parametri di farmacocinetica e farmacodinamica (PK/PD) delle 4 dosi di BAY 86-6150 con una dose fissa di eptacog alfa (attivato) in un ulteriore sottogruppo delle suddette coorti,
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male subjects
- 12 to 62 years-of-age
- History of moderate or severe congenital hemophilia A or B with inhibitors to FVIII or FIX
- 4 or more bleeding episodes in the last 6 months before enrollment. |
Soggetti di sesso maschile tra 12 e 62 anni con anamnesi di emofilia A o B congenita moderata o grave con inibitori contro FIII o FIX che abbiano avuto 4 o più episodi emorragici negli ultimi 6 mesi prima dell'arruolamento. |
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E.4 | Principal exclusion criteria |
- Clinically relevant coagulation disorder other than congenital hemophilia A or B with inhibitors
- History of coronary and/or peripheral atherosclerotic disease
- Disseminated intravascular coagulopathy, or stage 2 hypertension
- Angina pectoris
- Myocardial infarction
- Transient ischemic attack
- Stroke
- Congestive heart failure
- Thromboembolic event |
Disordini della coagulazione clinicamente rilevanti diversi da emofilia a o B congenite con inibitori -storia di patologia aterosclerotica coronarica e/o periferica - Coagulopatia intravascolare disseminata o ipertensione di fase 2 - angina pectoris - Infarto miocardico - Attacco ischemico transitorio - Ictus - Insufficienza cardiaca congestizia - Evento tromboembolico |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Successful treatments of bleeding episodes. (A bleed was defined as successfully treated, if no administration of rescue medication was required.)
2. Proportion of successful treatments of bleeding episodes on subject level. (Proportion of successful treatments of bleeding
episodes was calculated as number of bleeding episodes treated successfully - without rescue medication - divided by the total number of bleeding episodes on a dose level.) |
L’endpoint primario è rappresentato dal successo del trattamento, definito come:
• Livello di emorragia: nessuna somministrazione del farmaco di emergenza [vero/falso].
• Livello soggettivo: la percentuale individuale di successo viene calcolata come il numero di episodi emorragici trattati con successo (senza farmaco di emergenza) diviso per il numero totale di episodi emorragici verificatisi con un certo livello di dose. Un responder è definito come la soggetto che ha almeno il 70% di episodi emorragici trattati senza il farmaco di emergenza.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. 10 hours after each bleed
2. 10 hours after each bleed |
1. 10 ore dopo ogni sanguinamento
2. 10 ore dopo ogni sanguinamento
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E.5.2 | Secondary end point(s) |
1. Time to stop the bleed.
2. Number of injections needed to stop the bleeding episode.
3. Effectiveness of treatment as rated by the subject's assessment (very effective, effective, partially effective, not effective).
4. Participant's reported outcome as assessed by Euro QoL (EQ-5D).
5. Participant's reported outcome as assessed by Brief Pain Inventory.
6. Participant's reported outcome as assessed by Work Productivity and Activity Impairment Questionaire. |
•Misure dell’esito riferite dal soggetto:
- EuroQol, (EQ-5D) (Questionario Europeo sulla qualità della vita)
- Brief Pain Inventory (BPI) (Breve inventario del dolore) e misure del dolore a singolo item (item n.° 3 e n.° 6 del BPI).
- Work Productivity and Activity Impairment Questionnaire (WAPI) (Questionario sulla produttività lavorativa e sull’alterazione dell’attività)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1., 2. & 3.: 10 hours after each bleed
4. & 6.: 14 days after last exposure to BAY86-6150
5.: 7 days after last exposure to BAY86-6150 |
1., 2. e 3.: 10 ore dopo ogni sanguinamento
4. e 6.: 14 giorni dopo l'ultima esposizione a BAY86-6150
5.: 7 giorni dopo l'ultima esposizione a BAY 86-6150 |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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) | Yes |
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.8.1.7.1 | Other trial design description |
Part A & B: non-controlled design / PK/PD: randomized, controlled, crossover design |
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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 | 9 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
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 | 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 |
European Union |
Argentina |
Australia |
Brazil |
Bulgaria |
Chile |
China |
Colombia |
Denmark |
France |
Germany |
Hungary |
India |
Israel |
Italy |
Japan |
Korea, Republic of |
Mexico |
Netherlands |
New Zealand |
Poland |
Romania |
Singapore |
South Africa |
Sweden |
Taiwan |
Turkey |
Ukraine |
United Kingdom |
United States |
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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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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 | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |