E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pulmonary Arterial Hypertension (PAH) |
lpertensione arteriosa polmonare (PAH) |
|
E.1.1.1 | Medical condition in easily understood language |
Cardiovascular Disease |
Malattia cardiovascolare |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
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 | 10038738 |
E.1.2 | Term | Respiratory, thoracic and mediastinal disorders |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal 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 |
The primary objective of this open-label, LTFU study is to evaluate the long-term safety and tolerability of sotatercept when added to background PAH therapy in adult participants with PAH. |
L'obiettivo primario di questo studio LTFU in aperto è quello di valutare la sicurezza e la tollerabilità a lungo termine di sotatercept quando viene aggiunto alla terapia di base per la PAH in partecipanti adulti con PAH. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objective is to follow participants from parent sotatercept studies that were treated with sotatercept or placebo and assess continued efficacy |
L'obiettivo secondario è quello di seguire i partecipanti provenienti dagli studi originari su sotatercept che sono stati trattati con sotatercept o placebo e valutare l'efficacia continuata. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Eligible participants must meet the following criteria to be enrolled in the study: 1. Participants must have completed their current respective PAH sotatercept clinical study, must have completed the parent study requirements, and must not have discontinued early. 2. Participants must be willing to adhere to the study visit schedule and understand and comply with all protocol requirements. 3. Participants must have the ability to understand and provide written informed consent f. 4. Females of childbearing potential must: a. Have a negative pregnancy tests as verified by the investigator prior to starting study drug administration; she must agree to ongoing pregnancy testing during the course of the study and until 8 weeks after the last dose of the study drug. b. If sexually active, have used, and agree to continue to use highly effective contraception without interruption, for at least 28 days prior to starting the investigational product, during the study (including dose interruptions), and for 16 weeks (112 days) after discontinuation of study drug. c. Refrain from breastfeeding a child or donating blood, eggs, or ovum for the duration of the study and for at least 16 weeks (112 days) after the last dose of study drug. 5. Male participants must: a. Agree to use a condom, defined as a male latex condom or non-latex condom NOT made out of natural (animal) membrane (e.g., polyurethane), during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for at least 16 weeks (112 days) following investigational product discontinuation, even if he has undergone a successful vasectomy b. Refrain from donating blood or sperm for the duration of the study and for 16 weeks (112 days) after the last dose of study drug. 6. Participants must agree not to participate in any other trials of investigational drugs/devices while they are enrolled in the A011-12 study |
I partecipanti eleggibili devono soddisfare i seguenti criteri per essere arruolati nello studio: 1. I partecipanti devono aver completato il loro rispettivo studio clinico in corso su sotatercept per la PAH e i relativi requisiti, e non devono averlo interrotto anticipatamente. 2. I partecipanti devono essere disposti ad aderire al programma di visite dello studio e comprendere e rispettare tutti i requisiti del protocollo. 3. I partecipanti devono essere in grado di comprendere e fornire un consenso informato scritto. 4. Le partecipanti di sesso femminile in età fertile devono: a. Avere un test di gravidanza negativo come verificato dallo sperimentatore prima di iniziare la somministrazione del farmaco in studio; accettare di sottoporsi a un test di gravidanza su base continuativa durante il corso dello studio e fino a 8 settimane dopo l'ultima dose del farmaco in studio. b. Se sessualmente attive, aver usato e accettare di continuare ad usare una contraccezione altamente efficace senza interruzione, per almeno 28 giorni prima di iniziare il prodotto sperimentale, durante lo studio (comprese le interruzioni della dose) e per 16 settimane (112 giorni) dopo l'interruzione del farmaco in studio. c. Astenersi dall'allattamento o dal donare sangue o ovuli per tutta la durata dello studio e per almeno 16 settimane (112 giorni) dopo l'ultima dose del farmaco in studio. 5. I partecipanti di sesso maschile devono: a. Accettare di usare un preservativo, definito come preservativo maschile in lattice o non in lattice che NON sia costituito da membrana naturale (animale) (es. poliuretano), durante il contatto sessuale con una donna in gravidanza o in età fertile durante la partecipazione allo studio, durante le interruzioni della dose e per almeno 16 settimane (112) giorni dopo l'interruzione del trattamento con il prodotto sperimentale, anche in caso di vasectomia eseguita con successo. b. Astenersi dal donare sangue o sperma per tutta la durata dello studio e per 16 settimane (112 giorni) dopo l'ultima dose del farmaco in studio. 6. I partecipanti devono accettare di non partecipare ad altre sperimentazioni di farmaci/dispositivi sperimentali mentre sono arruolati nello studio A011-12. |
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E.4 | Principal exclusion criteria |
Participants will be excluded from the study if any of the following criteria are met: 1. Not enrolled in a PAH parent study at the time of enrollment. 2. Missed more than the equivalent of 4 consecutive doses between the end of parent study and the start of this study. 3. Presence of an ongoing serious adverse event (SAE) that occurred during a PAH sotatercept clinical study that is assessed to be possibly or probably related to sotatercept. 4. Pregnant or breastfeeding females. |
I partecipanti sono esclusi dallo studio se soddisfano uno dei seguenti criteri: 1. Non arruolati in uno studio originario per PAH al momento dell'arruolamento. 2. Più dell'equivalente di 4 dosi consecutive saltate tra la fine dello studio originario e l'inizio di questo studio. 3. Presenza di un evento avverso grave in corso che si è verificato durante uno studio clinico su sotatercept per la PAH che è valutato come possibilmente o probabilmente correlato a sotatercept. 4. Partecipanti di sesso femminile in gravidanza o allattamento. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The following endpoints will be evaluated as a measure of safety and tolerability: • AEs • Anti-drug antibodies (ADA) • Clinical laboratory assessments (hematology and serum chemistry) • Vital signs • 12-lead electrocardiogram (ECG) |
I seguenti endpoint saranno valutati come misura della sicurezza e della tollerabilità: • AE • Anticorpi anti-farmaco (ADA) • Valutazioni cliniche di laboratorio (ematologia e chimica del siero) • Segni vitali • Elettrocardiogramma a 12 derivazioni (ECG) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
24 months and 48 months |
24 mesi e 48 mesi |
|
E.5.2 | Secondary end point(s) |
The following efficacy endpoints will be evaluated: • 6-minute walk distance • N-terminal pro-hormone B-type natriuretic peptide • World Health Organization functional class • Pulmonary vascular resistance • Overall survival • Simplified French Risk score |
Saranno valutati i seguenti endpoint di efficacia: • Distanza percorsa in 6 minuti • Frammento N-terminale del proormone del peptide natriuretico di tipo B • Classe funzionale secondo l’Organizzazione Mondiale della Sanità • Resistenza vascolare polmonare • Sopravvivenza globale • Punteggio di rischio semplificato francese |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
24 months and 48 months |
24 mesi e 48 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 | 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 | 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 | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
|
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.8.2.4 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 83 |
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 |
Canada |
Colombia |
Israel |
Korea, Republic of |
Mexico |
New Zealand |
Serbia |
Taiwan |
United States |
Austria |
Belgium |
Croatia |
Denmark |
France |
Germany |
Ireland |
Italy |
Netherlands |
Poland |
Portugal |
Spain |
Sweden |
Switzerland |
United Kingdom |
Czechia |
Argentina |
Greece |
|
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
|
A participant is considered to have completed the study if he/she has completed all phases of the study, including the EOT Visit and Follow-up Visit. The End of Study is defined as when the last participant completes the last visit. |
Un partecipante avrà completato lo studio quando tutte le fasi dello studio saranno state completate, comprese le visite di EOT e Follow-up. La fine dello studio è definita come il momento in cui l'ultimo partecipante completa l'ultima visita. |
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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 | 7 |
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 | 7 |
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 |