Clinical Trials

Inclusion Criteria:

• Ages 18 and 80 years, inclusive.
• Diagnosis of Right Heart Catheterization (RHC)-confirmed WHO Group 1 PAH in any of the following 3 categories:
  • Idiopathic, primary, or familial pulmonary arterial hypertension (IPAH, PPH, or FPAH); OR
  • PAH associated with one of the following connective tissue diseases:
    • Systemic sclerosis (scleroderma); 
    • Limited scleroderma;
    • Mixed connective tissue disease;
    • Systemic lupus erythematosus;
    • Overlap syndrome;
    • Other autoimmune disorders; OR
  • PAH associated with:
    • Human immunodeficiency virus (HIV) infection with no evidence of opportunistic infection in the preceding 6 months;
    • Simple, congenital systemic-to-pulmonary shunts at least 1-year post-surgical repair;
    • Exposure to legal drugs, chemicals and toxins, such as fenfluramine, derivatives, other anorexigens, toxic rapeseed oil, or L-tryptophan.
• At the time of PAH diagnosis, the patient must have had a ventilation/perfusion (V/Q) scan, computerized tomography angiogram, or pulmonary arteriogram that rules out chronic thromboembolic pulmonary hypertension (CTEPH).
• Previous diagnosis with PAH, but with the following conditions:
  • Stable PAH without significant adjustments of disease-specific background PAH therapy, at least 3 months prior to the CPET procedure. Stable is defined as no change in PAH-specific drug therapy within 3 months of Screening Visit 1, and for the duration of the study, and no change in dose of PAH-specific drug within 1 month of Screening; AND
  • If on corticosteroids, has been receiving a stable dose of ≤ 20 mg/day of prednisone (or equivalent dose of other corticosteroid) for at least 30 days prior to the baseline CPET.
• PFT within 36 months prior to the baseline CPET.
• Has had RHC performed within 36 months of Screening. that is consistent with the diagnosis of PAH.
• Has WHO/NYHA functional class II-IV symptomatology.
• On stable oral PAH disease-specific background therapy of up to 2 oral therapies (any combination of an ERA, PDE5 inhibitor, and/or a prostacyclin or prostacyclin receptor agonist) and/or inhaled therapy. Stable is defined as no change in PAH-specific drug therapy within 3 months of Screening Visit 1, and for the duration of the study, and no change in dose of PAH-specific drug within 1 month of Screening.
• Must be able to walk a distance of at least 50 meters on the 6MWT. This will be determined using the mean of the two 6MWT results done between Visits 1 and 2.
• If the subject is taking the following concomitant medications which may affect PAH, the subject must be on a stable therapeutic dose for at least 1 month prior to the start of Screening and the dosage maintained throughout the study.
  • Vasodilators;
  • Anticoagulants.

Exclusion Criteria:

• Baseline systemic hypotension defined as MAP < 50 mmHg or SBP < 90 mmHg at Screening.
• History of chronic uncontrolled asthma.
• Requirement of intravenous inotropes therapies within 30 days prior to the baseline CPET procedure.
• Use of intravenous PAH medications.
• Use of oral, topical, or inhaled nitrates within 2 weeks prior to the baseline CPET procedure.
• Has uncontrolled systemic hypertension a
• Portopulmonary hypertension, portal hypertension, or chronic liver disease determined to be Child-Pugh B or C, including hepatitis B virus and/or hepatitis C virus (HCV).
• Subjects who have had a previous infection with HCV and who have a negative viral load after receiving a course of curative treatment are allowed.
• Evidence or history of left-sided heart disease and/or clinically significant cardiac disease.
• History of atrial septostomy.
• History of known uncorrected right-to-left shunt, persistently patent foramen ovale, or known Eisenmenger's physiology.
• Paroxysmal or uncontrolled atrial fibrillation.
• Diagnosis of Down syndrome.
• Chronic renal insufficiency as defined by serum creatinine > 2.5 mg/dL or has an estimated glomerular filtration rate (eGFR) < 30 mL/min utilizing the Modification of Diet in Renal Disease (MDRD) Study equation at Screening or requires dialytic support.
• Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value that is ≥ 3 x the upper limit of the normal range.
• Platelets below 50,000/?L at Screening.
• Hemoglobin (Hgb) concentration < 9 g/dL at Screening.
• For subjects with HIV-associated PAH, any of the following:
  • Concomitant active opportunistic infections within 6 months prior to Screening;
  • Detectable viral load within 3 months of Screening;
  • Cluster designation 4 (CD4+) T-cell count < 200/mm3 within 3 months prior to Screening;
  • Changes in antiretroviral regimen within 3 months prior to Screening.
• Malignancy within 5 years prior to Screening with the exception of localized non-metastatic basal cell carcinoma of the skin and in-situ carcinoma of the cervix excised with curative intent.
• History of hypotension including fainting, syncope, orthostatic hypotension, and/or vasovagal reactions.
• Vision loss due to non-arteritic anterior ischemic optic neuropathy or other optic perfusion impairment.
• History of sudden sensorineural hearing loss.
• Male subjects with a corrected QT interval using Fridericia's formula (QTcF) > 450 msec and female subjects with QTcF > 470 msec on electrocardiogram (ECG) measured at Screening.
• Participation in a drug, device, or other interventional clinical study, other than post-marketing observational extension study, within 30 days prior to Screening.
• Participation in the active phase (other than the maintenance phase) of a pulmonary rehabilitation/structured exercise training program within 6 months prior to Screening.

Eligibility last updated 8/8/22. Questions regarding updates should be directed to the study team contact.