E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Emofilia A, Emofilia B |
Hemophilia A or Hemophilia B |
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E.1.1.1 | Medical condition in easily understood language |
Hemophilia is an inherited bleeding disorder in which the blood does not clot normally and can result in internal bleeding into the muscles and joints. |
L'emofilia è un disordine emorragico ereditato in cui il sangue non coaugula normalmente e può provocare sanguinamenti interni nei muscoli e nelle articolazioni. |
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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 | 10060614 |
E.1.2 | Term | Hemophilia B (Factor IX) |
E.1.2 | System Organ Class | 100000004850 |
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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 | 10060613 |
E.1.2 | Term | Hemophilia A (Factor VIII) |
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 |
To characterize the frequency of bleeding episodes while receiving fitusiran treatment, relative to the frequency of bleeding episodes while receiving factor or bypassing agent prophylaxis. |
Caratterizzare la frequenza degli episodi di sanguinamento durante l’assunzione del trattamento con fitusiran, in relazione alla frequenza degli episodi di sanguinamento durante l’assunzione della profilassi con fattore o agente bypassante. |
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E.2.2 | Secondary objectives of the trial |
To characterize the frequency of spontaneous bleeding episodes, the frequency of joint bleeding episodes in patients, and health related quality of life (HRQOL) in patients while receiving fitusiran treatment, relative to receiving factor or bypassing agent prophylaxis. |
Caratterizzare la frequenza degli episodi di sanguinamento spontaneo, la frequenza degli episodi di sanguinamento articolare nei pazienti e la qualità di vita correlata allo stato di salute (HRQOL) nei pazienti durante l'assunzione del trattamento con fitusiran, in relazione all’assunzione della profilassi con fattore o agente bypassante. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Males ≥12 years of age. - Severe hemophilia A or B (evidenced by a central laboratory FVIII <1% or FIX level ≤2% at Screening) with or without inhibitors - At least 1 bleeding episode in the last 12 months - AT activity ≥60% at Screening - Documented details of prophylactic treatment with factor concentrates or bypassing agents for the treatment of hemophilia A or B for at least 6 months - Willing and able to comply with the study requirements and to provide written informed consent and assent in the case of patients under the age of legal consent |
- Soggetti di sesso maschile di ≥12 anni d'età. - Emofilia A o B grave (FVIII <1% o livello FIX ≤2% allo Screening dimostrato da un laboratorio centrale) con o senza inibitori - Almeno un episodio di sanguinamento negli ultimi 12 mesi - Attività AT ≥60% allo Screening - Documentazione dettagliata di trattamento profilattico con concentrati di fattore o agenti bypassanti per il trattamento dell’emofilia A o B per almeno 6 mesi - Volontà e capacità di aderire ai requisiti dello studio e di fornire il consenso informato scritto e l'assenso nel caso di pazienti al di sotto dell'età per fornire il consenso legale
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E.4 | Principal exclusion criteria |
- Patients with known co-existing bleeding disorders other than hemophilia A or B - Patients with clinically significant liver disease - Patients known to be HIV positive and have a CD4 count <200 cells/μL - Patients with a history of arterial or venous thromboembolism - Estimated glomerular filtration rate ≤45 mL/min/1.73m2 (using the Modification of Diet in Renal Disease [MDRD] formula) - Patients with a co-existing thrombophilic disorder - Patients with a history of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc - Patients with a history of intolerance to SC injection(s) - Patients with an anticipated or planned need for surgery during the study - Any other conditions or comorbidities that would make the patient unsuitable for enrollment or could interfere with participation in or completion of the study, per Investigator judgement |
- Pazienti con problemi di sanguinamento noti concomitanti diversi dall'emofilia A o B - Pazienti con malattia epatica clinicamente significativa - Pazienti con positività nota all'HIV e una conta CD4 <200 cellule/μl - Pazienti con anamnesi di tromboembolia arteriosa o venosa - Velocità di filtrazione glomerulare stimata ≤45 ml/minuto/1,73 m2 (utilizzando la formula di modifica della dieta nella malattia renale [Modification of Diet in Renal Disease, MDRD]) - Pazienti con un disturbo trombofilico concomitante - Pazienti con anamnesi di molteplici allergie a farmaci o anamnesi di reazione allergica a un oligonucleotide o GalNAc - Pazienti con anamnesi di intolleranza alle iniezioni SC - Pazienti con necessità prevista o pianificata di intervento chirurgico nel corso dello studio - Qualsiasi altra condizione o comorbilità che renderebbe il paziente non idoneo all'arruolamento o potrebbe interferire con la partecipazione nello o con il completamento dello studio, secondo il giudizio dello Sperimentatore
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E.5 End points |
E.5.1 | Primary end point(s) |
Annualized bleeding rate (ABR) |
Tasso annuale di sanguinamento (ABR) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
through 13 months |
13 mesi |
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E.5.2 | Secondary end point(s) |
- Annualized spontaneous bleeding rate - Annualized joint bleeding rate - Haem-A-QOL score |
- Tasso annuale di sanguinamento spontaneo - Tasso annuale di sanguinamento articolare - Punteggio Haem-A-QOL
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
through 13 months |
13 mesi |
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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 | No |
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 | 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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Profilassi, Terapia standard |
Prophylaxis SOC |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 |
Australia |
Brazil |
Bulgaria |
Canada |
China |
Denmark |
France |
Germany |
Hungary |
Ireland |
Israel |
Italy |
Japan |
Korea, Republic of |
Malaysia |
Netherlands |
Portugal |
Russian Federation |
South Africa |
Spain |
Switzerland |
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 | 4 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |