E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
idiopathic pulmonary fibrosis (IPF) |
fibrosi polmonare idiopatica (FPI) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10021240 |
E.1.2 | Term | Idiopathic pulmonary fibrosis |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to demonstrate whether at least one dose strategy is superior to placebo in patients with IPF, in modifying the rate of decline of Forced Vital Capacity (FVC). |
L'obiettivo primario e' dimostrare se almeno una strategia di dosaggio sia superiore a placebo nel modificare il declino della capacita' vitale forzata in pazienti con fibrosi polmonare idiomatica (FPI). |
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E.2.2 | Secondary objectives of the trial |
Additional parameters will be assessed in order to differentiate between dose strategies on the basis of safety and efficacy |
Verranno indagati alcuni parametri aggiuntivi,al fine di differenziare tra strategie di dosaggio sulla base di tollerabilita' ed efficacia. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patient >= 40 years - Written informed consent signed prior to entry into the study - IPF diagnosed (according to ATS / ERS criteria) less than 5 years prior to screening visit. - HRCT within 12 months of randomisation and biopsy (the latter if needed to fulfil ATS/ERS criteria) centrally reviewed and consistent with diagnosis. - FVC >= 50 % of predicted value Predicted normal values will be calculated according to ESCS: Males : FVC predicted (L) = 5.76 x height (meters)- 0.026 x age (years) -4.34 Females : FVC predicted (L) = 4.43 x height (meters)- 0.026 x age (years) -2.89 - Single breath DLCO (corrected for Hb) 30 - 79% inclusive of predicted . Different sites may use different prediction formulas, based on the method used to measure DLco. In any case, the method used must be in compliance with the ATS/ERS guideline.Adjustment for haemoglobin: Males : DLCO predicted for Hb = DLCO predicted x (1.7Hb/[10.22+Hb]) Females : DLCO predicted for Hb = DLCO predicted x (1.7Hb/[9.38+Hb]) where Hb is expressed in g·dL-1 - PaO2 >= 55 mmHg (sea level to 1500 m) or 50 mmHg (above 1500 m) room air |
- Eta` >= 40 anni. - Consenso informato rilasciato per iscritto prima del reclutamento nello studio. -Diagnosi di IPF (secondo i criteri ATS/ERS) negli ultimi 5 anni precedenti la vista di screening. - Tomografia computerizzata ad alta risoluzione entro 12 mesi dalla randomizzazione e biopsia (questa ultima se richiesta per soddisfare i criteri ATS/ERS) valutata centralmente e consistente con la diagnosi. - Capacita` vitale forzata FVC >= 50% del teorico. Valori teorici secondo ESCS: Maschi: FVC teorico (L) = 5.76 x altezza (metri)- 0.026 x eta` (anni) -4.34 Femmine : FVC teorico (L) = 4.43 x altezza (metri)- 0.026 x eta` (anni) -2.89 6.DLCO singola (corretta per Hb) 30 - 79% comprensiva del teorico. Centri differenti possono usare formule differenti, sulla base del metodo usato per misurare il DLCO. In ogni caso, il metodo deve essere in accordo con la linea guida ATS/ERS. Aggiustamento per Hb: Maschi : DLCO teorico per Hb = DLCO teorico x (1.7Hb/[10.22+Hb]) Femmine : DLCO teorico per Hb = DLCO teorico x (1.7Hb/[9.38+Hb]) dove Hb e` espressa in g dL-1 - Pa O2 >= 55 mmHg (dal livello del mare a 1500 m) o 50 mmHg (> 1500 m slm) aria. |
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E.4 | Principal exclusion criteria |
- AST, ALT > 1.5 x ULN at screening (visit 1). - Bilirubin > 1.5 x ULN at screening (visit 1). - Relevant airways obstruction (i.e. pre-bronchodilator FEV1/FVC < 0.7) at screening(visit 1). - Continuous oxygen supplementation at randomisation (defined as >= 15 hours supplemental oxygen per day). - Active infection at screening or randomisation. - Neutrophils < 1500 / mm3 at screening(visit 1). - International normalised ratio (INR) > 1.5 and/or Partial thromboplastin time (PTT) > 1.5 x ULN at screening (visit 1). - Platelets < 100 000 /mL at screening (visit 1). - Haemoglobin < 9.0 g/dL at screening (visit 1). - In the opinion of the Investigator, patient is likely to have lung transplantation during study (but being on transplantation list is acceptable for participation). - Life expectancy for disease other than IPF < 2.5 years (Investigator assessment). - Other disease that may interfere with testing procedures or in judgement of Investigator may interfere with trial participation or may put the patient at risk when participating to this trial. Myocardial infarction during the previous 6 months Unstable angina during the previous month - Other investigational therapy received within 8 weeks prior to screening visit. - Women who are breast feeding or of child bearing potential not using a highly effective method of birth control for at least one month prior to enrolment (highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1 % per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomized partner). Female patients will be considered of childbearing potential unless surgically sterilized by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years. - Sexually active males not committing to using condoms during the course of the study (except if their partner is not of childbearing potential). - Known or suspected active alcohol or drug abuse. - Bleeding risk Known inherited predisposition to bleeding. Patients who require full-dose anticoagulation (e.g. vitamin K antagonists, heparin, hirudin etc). Patients who require full-dose antiplatelet (e.g. acetyl salicylic acid, clopidogrel etc) therapy. History of hemorrhagic CNS event within 12 months prior to screening (visit 1). Any of the following within 3 months prior to screening (visit 1): -Gross / frank haemoptysis or haematuria -Active gastro-intestinal bleeding or ulcers -Major injury or surgery. - Thrombotic risk Known inherited predisposition to thrombosis. History of thrombotic event (including stroke and transient ischemic attacks) within 12 months prior to screening (visit 1). - Surgical procedures planned to occur during trial period. - Coagulopathy. - Uncontrolled systemic arterial hypertension. |
- AST, ALT > 1.5 x limite superiore di normalita` allo screening (visita 1). Bilirubina > 1.5 x limite superiore di normalita` allo screening (visita 1). - Ostruzione aerea rilevante (FEV1/capacita` vitale forzata < 0.7 prima dei broncodilatatori) allo screening (visita 1). -Supplementazione continua di ossigeno alla randomizzazione (>= 15 ore/die). - Stato di infezione allo screening o alla randomizzazione. 6.Neutrofili < 1500 / mm3 allo screening (visita 1). - Rapporto internazionale normalizzato (INR) > 1.5 e/o tempo parziale di tromboplastina (PTT) > 1.5 x limite superiore di normalita` allo screening (visita 1). - Piastrine < 100 000 /mL at screening (visit 1). - Emoglobina < 9.0 g/dL allo screening (visita 1). - Paziente da trapiantare durante lo studio, a giudizio dello Sperimentatore (la presenza nella lista per il trapianto e` accettabile per l arruolamento). - Aspettativa di vita per malattie diverse dalla IPF < 2.5 anni (valutazione dello Sperimentatore). - Altre malattie che possano interferire con le procedure o a giudizio dello Sperimentatore possano interferire con la partecipazione allo studio o possano mettere il paziente a rischio in caso di partecipazione allo studio: Infarto del miocardio nei 6 mesi precedenti Angina instabile nel mese precedente - Altre terapie sperimentali ricevute nelle precedenti 8 settimane prima della visita di screening. - Donne che allattano o in eta` fertile che non usano un metodo anticoncezionale altamente efficace per almeno un mese prima dell arruolamento [i metodi anticoncezionali altamente efficaci sono quelli con basso tasso di insuccesso (meno del 1% per anno), come impianti, iniettabili, contraccettivi orali associati, alcune spirali, astinenza o vasectomia]. Le donne sono considerate in eta` fertile se non sterilizzate chirurgicamente, o non sottoposte a legatura delle tube, o in postmenopausa da almeno 2 anni. - Maschi sessualmente attivi che non accettano di usare il preservativo durante lo studio (salvo che la partner non sia a rischio di gravidanza. - Abuso attivo di alcool o droghe noto o sospetto. - Rischio di sanguinamento: Predisposizione nota ereditaria al sanguinamento Necessita` di anticoagulanti a dose piena (antagonisti della vitamina K, eparina, irudina) Necessita` di antiaggreganti piastrinici a dose piena (ASA, clopidogrel) Anamnesi di eventi emorragici del SNC nei 12 mesi precedenti lo screening (visita 1) Qualsiasi delle condizioni seguenti entro 3 mesi prima dello screening (visita 1): -emottisi severa/franca o ematuria -emorragia o ulcera gastrointestinale -trauma o chirurgia maggiori. - Rischio trombotico: Predisposizione ereditaria nota alla trombosi Anamnesi di eventi trombotici (compresi TIA e ictus) nei 12 mesi precedenti lo screening (visita 1). - Procedure chirurgiche programmate durante lo studio. - Coagulopatie. - Ipertensione arteriosa sistemica non controllata. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the rate of decline in FVC (expressed in mL per year), evaluated from baseline until 12 month of treatment, compared to placebo. |
L'end point primario e' il declino della capacita' vitale forzata, confrontato a placebo. La capacita' vitale forzata verra' misurata mediante tests spirometrici. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
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 | 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 | 5 |
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 | 11 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 40 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 40 |
E.8.9.2 | In all countries concerned by the trial days | 0 |