Ensayos clínicos

Inclusion Criteria:

• Signed and dated informed consent form. 
• Male and female subjects ≥ 18 (or the legal age of consent in the jurisdiction in which the study is taking place) and ≤ 85 years old at Screening (Visit 1).
• Subjects with diagnosis of CTEPH and inoperability confirmed by the corresponding Adjudication Committee (AC; Country-specific Adjudication Committee [CSAC] or Central Adjudication Committee [CAC]), defined as one of the following options:
  • Inoperable CTEPH (i.e., technically non-operable) with:
  • Diagnosis of CTEPH based on at least two of the following assessments performed in the 14-month period prior to randomization (Visit 2):
    • ventilation/perfusion (V/Q) scan;
    • pulmonary angiography (PA);
    • computed tomography pulmonary angiogram (CTPA); and/or
    • magnetic resonance angiography (MRA).
  • RHC (and LHC, if needed) * performed at least 90 days after start of full anticoagulation, showing:
    • PVR at rest ≥ 400 dyn.sec/cm5 or ≥5 Wood units for the hemodynamic cohort and PVR at rest ≥ 300  dyn.sec/cm^5 or ≥ 3.75 Wood units for the non-hemodynamic cohort;
    • Mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg;
    • Pulmonary arterial wedge pressure (PAWP) ≤ 15 mmHg or, if not available or unreliable, a left ventricular end diastolic pressure (LVEDP) ≤15 mmHg.
• Persistent/recurrent CTEPH after BPA, with:
  • Diagnosis of CTEPH based on at least one of the following assessments performed in the 14-month period prior to randomization (Visit 2) and after last interventional (BPA) treatment: V/Q scan, PA, CTPA or MRA.
  • RHC (and LHC, if needed)* performed at least 90 days after last interventional (BPA) treatment and at least 90 days after start of full anticoagulation, showing:
    • PVR at rest ≥ 400 dyn.sec/cm^5 or ≥ 5 Wood units for the hemodynamic cohort and PVR at rest ≥ 300 dyn.sec/cm^5 or ≥ 3.75 Wood units for the non-hemodynamic cohort;
    • mPAP ≥ 25 mmHg;
    • PAWP ≤ 15 mmHg, or, if not available or unreliable, an LVEDP ≤ 15 mmHg;
    • Persistent/recurrent CTEPH after PEA (including PEA followed by BPA) with:
    • Diagnosis of CTEPH based on at least one of the following assessments performed in the 14-month period prior to randomization (Visit 2) and after last surgical (PEA) or interventional (BPA) treatment:
    • V/Q scan, PA, CTPA or MRA.
    • RHC (and LHC, if needed)*performed at least 90 days after last surgical (PEA) or interventional (BPA) treatment and at least 90 days after start of full anticoagulation, showing:
    • PVR at rest ≥ 400 dyn.sec/cm^5 or ≥ 5 Wood units for the hemodynamic cohort and PVR at rest ≥ 300 dyn.sec/cm^5 or ≥ 3.75 Wood units for the non-hemodynamic cohort;
    • mPAP ≥ 25 mmHg;
    • PAWP ≤ 15 mmHg, or, if not available or unreliable, an LVEDP ≤ 15 mmHg.
• PH in WHO FC I–IV.
• Subject able to perform the 6MWT with a minimum distance of 100 m and a maximum distance of 450 m at Screening Visit (Visit 1).
• A woman of childbearing potentialis eligible only if all the following applies:
  • Negative serum pregnancy test at Screening and a negative urine pregnancy test at randomization
  • Agreement to undertake monthly urine pregnancy tests during the study and up to at least 30 days after study treatment discontinuation.
  • Agreement to use one of the methods of birth control from Screening visit up to at least 30 days after study treatment discontinuation.

* For the hemodynamic cohort, a historical RHC/LHC is allowed, provided it was performed within 30 days prior to Screening**, at least 90 days after last change in PH-specific therapies (ie, change in dose or initiation of new class of drugs) and as per guidance in Appendix 1. For the non-hemodynamic cohort, a historical RHC is allowed, provided it was performed within 6 months prior to Screening**.

** In case of rescreening in the hemodynamic cohort within 6 months of the first Screening Visit, the first screening RHC (and LHC, if needed) can be used, provided there have been no changes in PH-specific therapy(ies) since the first Screening Visit. In case of rescreening in the non-hemodynamic cohort within 6 months of the first Screening Visit, the first screening RHC (and LHC if needed) can be used. If no historical results are available, an RHC (and LHC, if needed) must be performed during the Screening period (as per guidance in Appendix 1 for the hemodynamic cohort).

Exclusion Criteria:

• Planned or current treatment with another investigational treatment up to 3 months prior to randomization.
• Any co-morbid condition that may influence the ability to perform a reliable and reproducible 6MWT, including use of walking aids (cane, walker, etc.).
• Any known factor or disease that might interfere with treatment compliance, study conduct or interpretation of the results, such as drug or alcohol dependence or psychiatric disease.
• Known concomitant life-threatening disease with a life expectancy < 12 months.