E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hemophilia A or Hemophilia B |
Hemofilia A o Hemofilia 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. |
La hemofilia es un trastorno hemorrágico hereditario en el que la sangre no coagula normalmente y puede dar lugar a sangrado interno en los músculos y articulaciones |
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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 | 10060613 |
E.1.2 | Term | Hemophilia A (Factor VIII) |
E.1.2 | System Organ Class | 100000011915 |
|
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 | 100000011913 |
|
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. |
Caracterizar la frecuencia de episodios hemorrágicos durante el tratamiento con fitusiran, en comparación con la frecuencia de episodios hemorrágicos durante la profilaxis con factores o agentes de puenteo |
|
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. |
Caracterizar la frecuencia de episodios hemorrágicos espontáneos ,la frecuencia de episodios hemorrágicos articulares y la calidad de vida relacionada con la salud (CVRS) en pacientes mientras recibían tratamiento con fitusirán en comparación con recibir factores o agentes de puenteo. |
|
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 |
Varones ≥ 12 años de edad Hemofilia A o B (demostrada por una determinación del laboratorio central de FVIII < 1% o FIX ≤ 2% en la selección) con o sin inhibidores Mínimo de 1 episodio hemorrágico en los 12 meses previos a la selección Actividad AT >= 60% en la selección Detalles documentados del tratamiento profiláctico para la hemofilia A o B con concentrados de factores o agentes de puenteo desde al menos 6 meses antes de la selección Disposición y capacidad para cumplir los requisitos del estudio y para dar su consentimiento informado por escrito, y su asentimiento en el caso de pacientes por debajo de la edad legal de consentimiento, conforme a los requisitos locales y nacionales. |
|
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 |
Trastornos hemorrágicos coexistentes conocidos diferentes de la hemofilia A o B Presencia de una hepatopatía clínicamente significativa VIH positivo conocido con recuento de CD4 < 200 células/μl Pacientes con antecedentes de tromboembolismo arterial o venoso Filtración glomerular estimada ≤ 45 ml/min/1,73 m2 (usando la fórmula de la Modificación de la dieta de la enfermedad renal [ MDRD ]). Pacientes con trastorno trombofílico coexistente Pacientes con antecedentes de alergias múltiples a fármacos o antecedentes de reacción alérgica a un oligonucleótido o a GalNAc Pacientes con antecedentes de intolerancia a inyecciones SC. Pacientes con necesidad prevista de una intervención quirúrgica durante el estudio o intervención quirúrgica cuya realización esté programada durante el estudio Cualquier transtorno (p. ej., problema médico) que en opinión del investigador determine que el paciente no sería apto para recibir el tratamiento el día 1, o que podría interferir en el cumplimiento del estudio, la seguridad del paciente o la participación del paciente hasta completar el período de tratamiento del estudio |
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E.5 End points |
E.5.1 | Primary end point(s) |
Annualized bleeding rate (ABR) |
Tasa anualizada de hemorragias (TAH) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Through 13 months |
Hasta 13 meses |
|
E.5.2 | Secondary end point(s) |
Annualized spontaneous bleeding rate
Annualized joint bleeding rate
Haem-A-QOL score |
Tasa anualizada de hemorragias espontáneas Tasa anualizada de hemorragias articulares puntuación Haem-A-QOL |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Through 13 months |
Hasta 13 meses |
|
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 |
profilaxis práctica clinica habitual |
Prophylaxis SOC |
|
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 | 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 |
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 |
|
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
|
|
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 | 10 |
E.8.9.1 | In the Member State concerned days | |
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 |