E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Idiopathic pulmonary fibrosis |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 17.0 |
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 |
- Change in pulmonary function (FVC% predicted) from baseline to week 52
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E.2.2 | Secondary objectives of the trial |
- Change in diffusion capacity of the lung for carbon dioxide (DLco)
- Change in pulmonary function: annualized rate of change in FVC
- Progression-free survival
- Acute IPF exacerbations
- Change in quality of life measurement
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age > or equal to 40 years at Visit 1
- Have a diagnosis of IPF based upon the ATS/ERS/JRS/ALAT consensus statement on IPF (Raghu et al. 2011) within the previous 5 years from time of screening and confirmed at baseline Have a central review assessment of HRCT performed during the screening period or < or equal to 12 months prior to the start of screening
- Patients from countries where a treatment is licensed/approved for IPF must additionally meet at least one of the following criteria to be eligible;
- Be unable to access a licensed therapy for IPF
- Treatment with a licensed therapy/therapies has been stopped for lack of efficacy or because of safety/tolerability reasons (a period of washout will be required; refer to Section 4.1.2)
- Be unwilling to be treated with a licensed/approved therapy and after having reviewed all available treatment options, the investigator and patient consider enrollment into the study appropriate
- FVC ≥ 40% and < or equal to 90% of predicted at screening
- Stable baseline lung function as evidenced by a difference of < 10% in absolute FVC measurements (in liters) between screening and Day 1/Visit 2 prior to randomization
- DLco > or equal to 25% of predicted at screening
- Adequate hematopoietic capacity, defined as the following:
- Hemoglobin > 8.5 g/dL
- ANC > or equal to 1000/microlitre
- Platelet count > or equal to 75,000/microlitre
- Adequate liver function, defined as the following:
- AST and ALT < or equal to 3 times the upper limit of normal (ULN)
- Total bilirubin < or equal to 1.5 x ULN or < 3 x ULN for patients with documented Gilbert syndrome
- Women of childbearing potential must use two methods of acceptable contraception including one highly effective method and a barrier method as directed by their physician during treatment for 7 months after completion of study treatment (or as per local requirement)
- Male patients must agree to remain abstinent or use a condom, even after a vasectomy, during sexual intercourse with female partners while being treated with vismodegib/placebo, and for 2 months after completion of study treatment.
- Agreement not to donate blood or blood products during the study and for at least 7 months (or as per local requirements) after the last dose of study treatment
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E.4 | Principal exclusion criteria |
- Prior treatment with vismodegib or any Hh pathway inhibitor
- Evidence of other known causes of ILD
- Hospitalization due to an exacerbation of IPF within 4 weeks prior to, or during, screening
- Lung transplant expected within 12 months of screening
- Evidence of clinically significant lung disease other than IPF
- Substantial emphysema on HRCT with degree of emphysema greater than fibrosis
- Class IV New York Heart Association chronic heart failure or historical evidence of left ventricular ejection fraction < 35%
- Known current malignancy or current evaluation for a potential malignancy
- Known immunodeficiency, including but not limited to HIV infection
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E.5 End points |
E.5.1 | Primary end point(s) |
- Change in pulmonary function (FVC% predicted) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- from baseline to week 52 |
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E.5.2 | Secondary end point(s) |
1. Change in DLco % predicted
2. Annualized rate of change in FVC (liters)
3. Progression free survival
4. Acute IPF exacerbations
5. Change in IPF-specific health-related quality of life |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. from baseline to week 52
2. from baseline to week 52
3. from randomization to the first occurrence of any of the following:
• Death from any cause
• Non-elective hospitalization from any cause
• ≥10% decline in FVC (L) (relative change) from baseline
4. from randomization to first event
5. from baseline to week 52 |
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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 | 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) | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
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 |
Chile |
France |
Germany |
Israel |
Italy |
Korea, Republic of |
Mexico |
New Zealand |
Peru |
Spain |
United States |
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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
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
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 | 3 |