E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Idiopathic pulmonary fibrosis (IPF) |
fibrosi polmonare idiopatica |
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E.1.1.1 | Medical condition in easily understood language |
Idiopathic pulmonary fibrosis (IPF) |
fibrosi polmonare idiopatica |
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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 | 21.1 |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- to evaluate the safety and tolerability of GLPG1690
- to characterize the PK and PD properties of GLPG1690
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- valutare la sicurezza e la tollerabilit¿ di GLPG1690 - caratterizzare le propriet¿ farmacocinetiche (PK) e farmacodinamiche (PD) di GLPG1690
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E.2.2 | Secondary objectives of the trial |
- to evaluate the change from baseline in FVC
- to explore the change in biomarkers in blood and BALF
- to evaluate the change in quality of life measures
- to evaluate the change in FRI parameters
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- valutare la variazione rispetto al basale della capacit¿ vitale forzata (FVC) - esplorare la variazione dei biomarcatori nel sangue e nel liquido di lavaggio broncoalveolare (BALF) ¿ valutare la variazione dei parametri di imaging funzionale dell¿apparato respiratorio (FRI) - valutare la variazione dei parametri di qualit¿ della vita (QOL)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects who are able and willing to sign the ICF as approved by the independent ethics committee (IEC). 2. Male or female subjects of non-child-bearing potential aged = 40 years on the day of signing the ICF. Note: Female subjects will be considered of non-childbearing potential if they are either sterilized, ovariectomized, hysterectomized, or postmenopausal (i.e., at least 24 months of amenorrhea in the absence of other biological or physiological causes [in case of doubt, the subject’s follicle stimulating hormone [FSH] levels will be determined and the subject will be considered postmenopausal if the FSH level is = 35 mIU/mL). 3. Subjects with a chest HRCT performed within 12 months prior to Screening visit. 4. Subjects with IPF diagnosed by a multidisciplinary team and confirmed by central review of the subject’s HRCT pattern and SLB (if available) 5. Subjects meeting all of the following criteria: a. FVC =50% predicted of normal b. Diffusing capacity for the lungs for carbon monoxide (DLCO) = 30% predicted of normal (corrected for hemoglobin) (see Appendix 3 for additional details) 6. Subjects with a forced expiratory volume in 1 second (FEV1)/FVC (Tiffeneau-Pinelli index) ratio = 0.70 (based on pre-bronchodilator spirometry). 7. Subjects who are on stable supportive care (e.g., supplemental oxygen, pulmonary rehabilitation) for at least 3 weeks prior to screening and during screening period. 8. Subjects must be in a stable condition and acceptable for study participation based upon the results of a medical history, physical examination, vital signs, 12-lead ECG, and laboratory evaluation. 9. Subjects must have an estimated minimum life expectancy of 12 months in the opinion of the investigator. 10. Male subjects and their female partners must use a highly effective method of birth control. 11. Subjects who are able to understand the importance of adherence to study treatment, study procedures and requirements, including the concomitant medication restrictions. |
1. Soggetti in grado e disposti a firmare il modulo di consenso informato (ICF) approvato dal comitato etico indipendente. 2. Soggetti di sesso maschile o di sesso femminile non potenzialmente fertili di età = 40 anni il giorno della firma del modulo di consenso informato. Nota: i soggetti di sesso femminile saranno considerati non potenzialmente fertili se si sono sottoposti a sterilizzazione, ovariectomia, isterectomia o sono in post-menopausa (ossia almeno 24 mesi di amenorrea in assenza di altre cause biologiche o psicologiche [in caso di dubbi, saranno determinati i livelli di ormone follicolo-stimolante [FSH] e il soggetto sarà considerato in post-menopausa se il livello di FSH è = 35 mUI/ml]). 3. Soggetti a cui è stata eseguita una tomografia computerizzata ad alta risoluzione del torace nei 12 mesi precedenti la visita di screening. 4. Soggetti con FPI diagnosticata da un équipe multidisciplinare e confermata da revisione centrale del pattern di HRCT e della biopsia polmonare chirurgica (SLB) (se disponibile) del soggetto. 5. Soggetti che soddisfano tutti i criteri seguenti: a. FVC = 50% del valore normale previsto b. Capacità di diffusione dei polmoni per il monossido di carbonio (DLCO) = 30% del valore normale previsto (corretto per l’emoglobina) 6. Soggetti con rapporto volume espiratorio forzato in 1 secondo (FEV1)/FVC (indice di Tiffeneau-Pinelli) = 0,70 (basato sulla spirometria pre-broncodilatatore). 7. Soggetti sottoposti a cure di supporto stabili (ad es. ossigeno supplementare, riabilitazione polmonare) da almeno 3 settimane prima dello screening e durante il periodo di screening. 8. I soggetti devono essere in condizioni stabili e accettabili per la partecipazione allo studio, sulla base dei risultati di anamnesi medica, esame obiettivo, parametri vitali, elettrocardiogramma (ECG) a 12 derivazioni e valutazione di laboratorio. 9. I soggetti devono avere un’aspettativa di vita minima stimata di 12 mesi, a parere dello sperimentatore. 10. I soggetti di sesso maschile e le loro partner femminili devono usare un metodo contraccettivo altamente efficace. 11. Soggetti in grado di comprendere l’importanza di attenersi al trattamento di studio, alle procedure e ai requisiti dello studio, incluse le limitazioni imposte sulle terapie farmacologiche concomitanti.
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E.4 | Principal exclusion criteria |
1. Subjects with a known hypersensitivity to any of the study drug ingredients or a history of a significant allergic reaction to any drug as determined by the investigator (e.g., anaphylaxis requiring hospitalization). 2. Subjects with a history of or a current immunosuppressive condition (e.g., human immunodeficiency virus [HIV] infection). 3. Subjects with a history of malignancy within the past 5 years (except for carcinoma in situ of the uterine cervix, basal cell carcinoma of the skin that has been treated with no evidence of recurrence, and prostate cancer medically managed through active surveillance or watchful waiting). 4. Subjects with clinically significant abnormalities detected on ECG regarding either rhythm or conduction (e.g., QT interval corrected for heart rate using Fridericia’s formula [QTcF] =450 ms, or a known long QT syndrome). Note: A first degree heart block will not be considered as a significant abnormality. 5. Subjects with acute IPF exacerbation within 6 weeks prior to screening and during the screening period. 6. Subject with a lower respiratory tract infection requiring antibiotics within 4 weeks prior to screening and during the screening period. 7. Subjects who have been smoking within 3 months prior to screening. 8. Interstitial lung disease (ILD) associated with known primary diseases (e.g., sarcoidosis, amyloidosis, etc.), exposures (e.g., radiation, silica, asbestos, coal dust, etc.), and drugs (e.g., amiodarone, etc.). 9. Subjects with a history of lung volume reduction surgery or lung transplant. 10. Subjects with an unstable cardiac or pulmonary disease (other than IPF) within 6 months prior to screening or during the screening period, including but not limited to: a. unstable angina pectoris, myocardial infarction b. congestive heart failure requiring hospitalization 11. Subjects with any clinical condition or circumstance that in the opinion of the investigator may make a subject unsuitable for inclusion or unable to complete the study or comply with study procedures and requirements. 12. Subjects with a contra-indication for bronchoscopy and bronchoalveolar lavage in the opinion of the investigator. 13. Subjects with an abnormal liver function defined as aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin >3 x upper limit of the normal range (ULN). 14. Subjects with an abnormal renal function defined as creatinine clearance < 50 mL/min using the Cockroft-Gault equation. 15. Subjects participating in a drug/device or biologic investigational research study (concurrently with the current study or within 8 weeks prior to screening). 16. Subjects using of any of the following therapies within 4 weeks before screening: a. Pirfenidone b. Nintedanib c. Warfarin d. Imatinib e. Ambrisentan f. Azathioprine g. Cyclophosphamide h. Cyclosporine A i. Prednisone at steady dose > 15 mg/day (for details, see Section 4.2.4) j. Any experimental IPF therapy 17. Subjects with active alcohol or substance abuse in the opinion of the investigator. |
1. Soggetti con ipersensibilità nota a uno qualsiasi dei componenti del farmaco di studio o con anamnesi positiva per reazione allergica significativa a qualsiasi farmaco, come stabilito dallo sperimentatore (ad es. anafilassi con necessità di ricovero ospedaliero). 2. Soggetti con anamnesi positiva per malattia immunosoppressiva o con malattia immunosoppressiva in atto (ad es. infezione da virus dell’immunodeficienza umana [HIV]). 3. Soggetti con anamnesi positiva per tumore maligno negli ultimi 5 anni (eccetto per carcinoma in situ della cervice uterina, carcinoma cutaneo basocellulare trattato senza evidenza di recidiva e tumore della prostata gestito dal punto di vista medico attraverso sorveglianza attiva o vigile attesa). 4. Soggetti con anomalie clinicamente significative rilevate all’ECG riguardanti il ritmo o la conduzione (ad es. intervallo QT corretto per la frequenza cardiaca mediante la formula di Fridericia = 450 ms o sindrome del QT lungo accertata). Nota: un blocco cardiaco di primo grado non sarà considerato un’anomalia significativa. 5. Soggetti con esacerbazione acuta della FPI nelle 6 settimane precedenti lo screening e durante il periodo di screening. 6. Soggetto con infezione delle vie respiratorie inferiori che richiede il trattamento con antibiotici nelle 4 settimane precedenti lo screening e durante il periodo di screening. 7. Soggetti che hanno fumato nei 3 mesi precedenti lo screening. 8. Pneumopatia interstiziale associata a malattie primarie note (ad es. sarcoidosi, amiloidosi, ecc.), esposizioni (ad es. radiazioni, silice, amianto, polvere di carbone, ecc.) e farmaci (ad es. amiodarone, ecc.). 9. Soggetti con anamnesi positiva per riduzione chirurgica del volume polmonare o trapianto di polmone. 10. Soggetti con malattia cardiaca o polmonare (diversa da FPI) instabile nei 6 mesi precedenti lo screening o durante il periodo di screening, incluse, a titolo non esaustivo: a. angina pectoris instabile, infarto del miocardio b. insufficienza cardiaca congestizia che richiede ricovero ospedaliero 11. Soggetti con condizione o circostanza clinica che, a parere dello sperimentatore, può rendere il soggetto inidoneo all’inclusione o non in grado di completare lo studio o di aderire alle procedure e ai requisiti dello studio. 12. Soggetti con controindicazione per broncoscopia e lavaggio broncoalveolare, a parere dello sperimentatore. 13. Soggetti con anomalia della funzione epatica, definita come aspartato aminotransferasi (AST), alanina aminotransferasi (ALT) o bilirubina > 3 volte il limite superiore della norma. 14. Soggetti con anomalia della funzione renale, definita come clearance della creatinina < 50 ml/min in base all’equazione di Cockroft-Gault. 15. Soggetti che partecipano a uno studio di ricerca sperimentale di un farmaco/dispositivo o biologico (in concomitanza con lo studio attuale o nelle 8 settimane precedenti lo screening). 16. Soggetti che utilizzano una delle terapie elencate sotto nelle 4 settimane precedenti la randomizzazione: a. Pirfenidone b. Nintedanib c. Warfarin d. Imatinib e. Ambrisentan f. Azatioprina g. Ciclofosfamide h. Ciclosporina A i. Prednisone a dose stabile > 15 mg/die j. Qualsiasi terapia sperimentale per la FPI 17. Soggetti con abuso attivo di alcol o di sostanze, a parere dello sperimentatore.
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Evaluation of Safety and tolerability
- AE monitoring
- Clinical laboratory examinations
- Vital signs
- Physical examination
- 12-lead ECG
2. Characterisation of PK and PD properties of the IMP
- Blood sampling (PK)
- Blood sampling (PD) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- AE monitoring: From signing informed consent until follow-up visit at multiple timepoints
- Clinical laboratory examinations, vital signs, physical examination: Screening, Baseline, W1 D7, W2 D14, W4 D28, W8 D56, W12 D84, Early Discontinuation Visit, Follow-up (W14 D98)
- 12-lead ECG: Screening, W1 D7, W2 D14, W4 D28, W8 D56, W12 D84, Early Discontinuation Visit, Follow-up (W14 D98)
- Blood sampling (PK): Baseline, W1 D7, W2 D14, W4 D28, W8 D56, W12 D84, Early Discontinuation Visit, Follow-up (W14 D98)
- Blood sampling (PD): Baseline, W4 D28, W12 D84, Early Discontinuation Visit, Follow-up (W14 D98) |
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E.5.2 | Secondary end point(s) |
- change from baseline in FVC, through spirometry
- change in biomarkers in blood and BALF
- change in FRI Parameters through HRCT
- change in quality of life (QOL) measures through SGRQ |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Spirometry: Screening, Baseline, W1 D7, W2 D14, W4 D28, W8 D56, W12 D84, Early Discontinuation Visit, Follow-up (W14 D98)
- Biomarker blood samples: Baseline, W4 D28, W12 D84, Early Discontinuation Visit, Follow-up (W14 D98)
- BALF sample: Baseline, W12 D84, Early Discontinuation Visit
- HRCT: Baseline, W12 D84, Early Discontinuation Visit
- SGRQ (QOL assessment): Baseline, W4 D28, W12 D84, Early Discontinuation Visit, Follow-up (W14 D98)
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarker analysis |
Biomarker analysis |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 |
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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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last contact with the last subject |
last contact with the last subject |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 12 |
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 | 12 |
E.8.9.2 | In all countries concerned by the trial days | 0 |