E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Systemic sclerosis associated with interstitial lung disease |
Sclerosi sistemica associata a malattia polmonare interstiziale |
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E.1.1.1 | Medical condition in easily understood language |
Systemic sclerosis is a disease characterized by abnormal and excess fibrosis, a hardening of tissues and organs. |
La sclerosi sistemica è una malattia caratterizzata da fibrosi anormale ed eccessiva, un indurimento di tessuti e organi. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025109 |
E.1.2 | Term | Lung involvement in systemic sclerosis |
E.1.2 | System Organ Class | 100000004855 |
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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 assess the safety and tolerability of PRA023 in SSc-ILD • To compare the annual rate of change from Baseline in forced vital capacity (FVC), in mL, of PRA023 vs. placebo over 50 weeks |
• Valutare la sicurezza e la tollerabilità di PRA023 nella SSc-ILD • Confrontare il tasso annuale di variazione dal Basale nella capacità vitale forzata (FVC), in ml, di PRA023 vs. placebo nell'arco di 50 settimane |
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E.2.2 | Secondary objectives of the trial |
• To compare the change from Baseline in FVC in mL of PRA023 vs. placebo at Week 50 • To compare the change from Baseline in FVC in percent predicted of PRA023 vs. placebo at Week 50 • To compare the annual rate of change in percent predicted FVC • To compare proportion of subjects with an improvement in the American College of Rheumatology Combined Response Index in Systemic Sclerosis (ACR CRISS) score at Week 50 |
• Confrontare la variazione dal Basale nella FVC, in ml, di PRA023 vs. placebo alla Settimana 50 • Confrontare la variazione dal Basale nella FVC, in percentuale prevista, di PRA023 vs. placebo alla Settimana 50 • Confrontare il tasso annuo di variazione della percentuale di FVC prevista • Confrontare la percentuale di soggetti con un miglioramento in 3 o più degli 5 indicatori "core" del punteggio dell'indice di risposta combinato per la sclerosi sistemica dell'American College of Rheumatology (ACR CRISS) di PRA023 rispetto al placebo alla Settimana 50 |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Other types of substudies Specify title, date and version of each substudy with relative objectives: Skin Biopsy Substudy: to assess change in histology and protein expression Pharmacokinetic Substudy: Fully characterize PK of PRA023 in subjects with SSc-ILD
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Altre tipologie di sottostudi specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Skin Biopsy Substudy: to assess change in histology and protein expression Pharmacokinetic Substudy: Fully characterize PK of PRA023 in subjects with SSc-ILD
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E.3 | Principal inclusion criteria |
1. Confirmed diagnosis of systemic sclerosis with onset of disease < or =5 years ago 2. Diffuse cutaneous scleroderma 3. Systemic sclerosis related to interstitial lung disease confirmed by HRCT 4. FVC > or = 45% of predicted normal 5. Diffusing capacity of lung for carbon monoxide (DLCO) > or = 45% of predicted normal 6. Stable dosing of myocphenolate mofetil (MMF), methotrexate (MTX) or azathioprine, as well as corticosteroids 7. Able to provide written informed consent and understand and comply with the requirements of the study |
1. Confermata insorsgenza di SSc < o = 5 anni prima 2. Sclerodermia cutanea diffusa 3. SSc come malattia fibrotica dei polmoni confermata mediante HRCT 4. FVC > o = 45% rispetto al valore normale previsto. 5. Capacità di diffusione polmonare del monossido di carbonio (DLCO) > o = 45% rispetto al valore normale previsto 6. Dosaggi stabili di Micofenolato mofetile , metotrexato, azatioprina e corticosteroidi 7. Fornire il consenso informato scritto e comprendere e rispettare i requisiti dello studio |
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E.4 | Principal exclusion criteria |
1. WOCBP and men with female partners of childbearing potential who are unwilling or unable to use two highly effective methods of contraception to avoid pregnancy for the entire study period and for up to 12 weeks after the last dose of study drug. 2. Airway obstruction per pulmonary function test (PFT) or Clinically significant pulmonary arterial hypertension. 3. Current clinical diagnosis of another inflammatory connective tissue disease disease 4. Any active infections, a serious infection within the past 3 months, or chronic bacterial infection 5. Current smoker or smoking within 6 months of screening 6. Subjects in the opinion of the investigator that are at an unacceptable risk for participation in the study 7. Subjects who meet the protocol criteria for important laboratory exclusion criteria |
1. WOCBP e uomini con partner di sesso femminile in età fertile che non sono disposti o non sono in grado di usare due metodi contraccettivi altamente efficaci per evitare la gravidanza per l'intero periodo dello studio e fino a 12 settimane dopo l'ultima dose del farmaco in studio. 2. Ostruzione delle vie aeree (PFT) o Ipertensione arteriosa polmonare (PAH) clinicamente significativa. 3. Attuale diagnosi clinica di un'altra malattia infiammatoria del tessuto connettivo ( 4. Qualsiasi infezione attiva, un'infezione grave negli ultimi 3 mesi o un'infezione batterica cronica 5. Fumatore attuale o fumatore entro 6 mesi dallo screening 6. Soggetti a giudizio dello sperimentatore che corrono un rischio inaccettabile per la partecipazione allo studio 7. Soggetti che soddisfano i criteri del protocollo per importanti criteri di esclusione di laboratorio |
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E.5 End points |
E.5.1 | Primary end point(s) |
• The proportion of subjects reporting adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, and markedly abnormal laboratory values • To compare the annual rate of change from Baseline in FVC, in mL, of PRA023 vs. placebo over 50 weeks |
• Proporzione di soggetti che riferiscono eventi avversi (AE), eventi avversi seri (SAE), AE che portano all'interruzione del trattamento e valori di laboratorio marcatamente anomali • Confrontare il tasso annuale di variazione dal Basale nella FVC, in ml, di PRA023 vs. placebo nell'arco di 50 settimane |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• To compare the change from Baseline in FVC • To compare the annual rate of change in percent FVC • To compare the change from Baseline in HRCT • To compare proportion of subjects with an improvement of the ACR CRISS score |
• Confrontare la variazione dal Basale nella FVC • Confrontare il tasso annuale di variazione nella FVC, in percentuale prevista • Confrontare la variazione dal Basale nella HRCT • Confrontare la percentuale di soggetti con un miglioramento del punteggio ACR CRISS |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 39 |
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 |
Canada |
Israel |
United States |
Belgium |
France |
Germany |
Hungary |
Italy |
Norway |
Poland |
United Kingdom |
Netherlands |
Spain |
Switzerland |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |