| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| pulmonary hypertension associated with idiopathic interstitial pneumonias |
|
| E.1.1.1 | Medical condition in easily understood language |
| high blood pressure in the blood vessels of the lungs associated with interstitial pneumonias of unknown cause |
|
| 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 | 17.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10037406 |
| E.1.2 | Term | Pulmonary hypertension secondary |
| E.1.2 | System Organ Class | 100000004855 |
|
| 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 |
| To evaluate the efficacy and safety of 26-weeks of treatment with riociguat vs. placebo in patients with symptomatic PH associated with IIP |
|
| E.2.2 | Secondary objectives of the trial |
Time to clinical worsening as evidenced by the first of any of the following four events:
•All-cause mortality
•Worsening of WHO functional class.
•Need for hospitalization due to worsening cardiopulmonary status, attributable to progression of disease (including but not limited to increased shortness of breath or increased leg swelling)
•15% decrease in the 6MWD test
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Men or women aged from ≥18 to ≤80 years
2.Diagnosed with one of the following (confirmed using a multidisciplinary approach, as per ATS/ERS/JRS/ALAT guidelines [1]):
-Major IIPs diagnosis or suspected as one of the following:
Idiopathic pulmonary fibrosis
Idiopathic nonspecific interstitial pneumonia
Respiratory bronchiolitis–interstitial lung disease
Desquamative interstitial pneumonia
Cryptogenic organizing pneumonia
Acute interstitial pneumonia
-Rare IIPs diagnosis by one of the following:
Idiopathic lymphoid interstitial pneumonia
Idiopathic pleuroparenchymal fibroelastosis
-Unclassifiable idiopathic interstitial pneumonias
3.FVC ≥ 45 %
4.6MWD ≥ 150 m to ≤ 450 m (under stable O2 supplementation via nasal cannula)
5.Diagnosis of PH confirmed by right heart catheter (RHC) with mPAP ≥ 25 mmHg and PAWP ≤15 mmHg at rest
6.Systolic blood pressure (SBP) ≥ 95 mmHg and no signs or symptoms of hypotension
7.WHO functional class II-IV
8.Women of childbearing potential can only be included in the study if a pregnancy test is negative. Women of childbearing potential must agree to use adequate contraception when sexually active. ‘Adequate contraception’ is defined as any combination of at least 2 effective methods of birth control, of which at least one is a physical barrier (e.g. condoms with hormonal contraception or implants or combined oral contraceptives, certain intrauterine devices). Adequate contraception is required from the signing of the informed consent form up until 4 weeks after the last study drug administration
|
|
| E.4 | Principal exclusion criteria |
1. Known significant left heart disease:
- Pulmonary venous hypertension indicated by baseline pulmonary capillary wedge pressure > 15 mmHg
- Symptomatic coronary artery disease
- Systolic left-ventricular dysfunction with an left ventricular ejection fraction (LVEF) <45%
2. Active state of hemoptysis or pulmonary hemorrhage, including those events managed by bronchial artery embolization
3. Any history of bronchial artery embolization or massive hemoptysis within 3 months prior to screening. Massive hemoptysis being defined as acute bleeding >240 mL in a
24-hour period or recurrent bleeding >100 mL/d over several days
4. History of acute lung infection or acute exacerbation within 4 weeks prior to screening
5. Reasonable likelihood of receiving a lung transplant within the 26 week main study period
6. Pulmonary veno-occlusive disease
7. Difference > 15% between the two baseline 6MWD test
8. Saturation of peripheral oxygen (SpO2) remains < 92 % with up to 6 L/minute supplemental oxygen delivered by nasal cannula at rest
9. Forced expiratory volume in one second (FEV1)/FVC <0.65 after bronchodilator administration
10. CO2 > 45 mmHg
11. Other known cause of ILD including:
a. connective tissue disease
b. sarcoidosis
c. chronic hypersensitivity pneumonitis
d. significant environmental exposure likely to be the cause of the patients ILD (such as asbestos or silica exposure)
12. Extent of emphysema greater than the extent of fibrotic changes (honeycombing, reticular changes) on HRCT scan
13. Initiation or change in cytotoxic, immunosuppressive, cytokine modulating therapy within 3 months prior to screening. Such agents might include azathioprine, cyclophosphamide, corticosteroids, etanercept, tumor necrosis factor alpha (TNFα) inhibitors and others
14. Pirfenidone and any other drug approved specifically for IPF initiated within 3 months prior to screening
15. Any specific treatment for PAH/PH within 3 months prior to screening
16. Active smoking of tobacco of any type or quantity
17. Active participation in a Pulmonary Rehabilitation program, defined as a structured exercise and rehabilitation program supervised by a physician, respiratory therapist and/or a physiotherapist. Patients who have completed a course of Pulmonary Rehabilitation and are in the maintenance phase of the program are eligible for study enrollment
18. Concomitant use of the following medication: nitrates or NO donors (such as amyl nitrite) in any form, phosphodiesterase 5 inhibitors (such as sildenafil, tadalafil, vardenafil) and non-specific phosphodiesterase (PDE) inhibitors (theophylline, dipyridamole),
19. Severe hepatic impairment (Child Pugh C)
20. Creatinine clearance < 15 ml/min or on dialysis
21. Pregnant women (i.e. positive pregnancy test or other signs of pregnancy), or breast feeding women, or women of childbearing potential not using adequate contraception (as defined in the aforementioned inclusion criterion) and not willing to agree to 4-weekly pregnancy testing from Visit 1(first administration of study drug) onwards until 4 weeks after last study drug intake
22. Previous randomization to treatment during this study
23. Participation in another clinical study with an investigational drug or a medical device within 30 days prior to randomization (phase I-III clinical studies). Active participation in an early access program for an IPF agent, specifically pirfenidone or nintedanib
24. Active neurologic, orthopedic or musculoskeletal disorder that is likely to affect performance of the 6MWD test
25. Hypersensitivity to the investigational drug |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| the mean change in 6 minute walking distance from baseline to week 26 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Time to clinical worsening as evidenced by the first of any of the following four events:
All-cause mortality
Need for hospitalization due to worsening cardiopulmonary status, attributable to
progression of disease (including but not limited to increased shortness of breath or
increased leg swelling)
15% decrease in the 6MWD test
Worsening of WHO functional class.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| 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 | No |
| 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.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 24 |
| 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 |
| Belgium |
| Canada |
| France |
| Germany |
| Italy |
| Japan |
| Spain |
| Switzerland |
| United Kingdom |
| United States |
|
| 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 | |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 8 |
| 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 |
Print
