Efficacy and Safety of Riociguat in Patients With Symptomatic Pulmonary Hypertension (PH) Associated With Idiopathic Interstitial Pneumonias (IIP)

Number of participants with Adverse Events (AEs) will be reported in Adverse Events section.

- Inclusion Criteria:

- Men or women aged from ≥18 to ≤80 years

- Diagnosed with one of the following (confirmed using a multidisciplinary approach, as
per ATS(American Thoracic Society) / ERS(European Respiratory Society) / JRS (Japanese
Respiratory Society) / ALAT(Latin American Thoracic Association) guidelines:

- Major IIPs (idiopathic interstitial pneumonias) 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

- Forced Vital Capacity (FVC) ≥ 45 %

- 6MWD (6 minutes walking distance) ≥ 150 m to ≤ 450 m {under stable O2(oxygen)
supplementation via nasal cannula}

- Diagnosis of PH (pulmonary hypertension) confirmed by right heart catheter (RHC) with
(mean artery pulmonary artery pressure )mPAP ≥ 25 mmHg and (pulmonary artery wedge
pressure)PAWP ≤15 mmHg at rest

- Systolic blood pressure (SBP) ≥ 95 mmHg and no signs or symptoms of hypotension

- WHO functional class II-IV

- 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

- Exclusion Criteria:

- 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%

- Active state of hemoptysis or pulmonary hemorrhage, including those events managed by
bronchial artery embolization

- 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

- Difference > 15% between the eligibility and the baseline 6MWD test

- Forced expiratory volume in one second (FEV1) / Forced Vital Capacity (FVC) <0.65
after bronchodilator administration

- Initiation in cytotoxic, immunosuppressive, cytokine modulating therapy initiated
within 3 months prior to screening. Such agents might include. azathioprine,
cyclophosphamide, corticosteroids, etanercept, tumor necrosis factor alpha (TNFα)
inhibitors and others

- Any specific treatment for (pulmonary arterial hypertension) PAH/PH (pulmonary
hypertension )within 3 months prior to screening

- Concomitant use of the following medication: nitrates or (nitric oxide) 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),

- 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