"A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Oral Inhalation of Seralutinib for the Treatment of Pulmonary Arterial Hypertension (PAH)"

To evaluate the effect of seralutinib compared to placebo on exercise capacity after 24 weeks of treatment when added to background PAH disease-specific medication

Inova Fairfax Medical Campus
3300 Gallows Rd
Falls Church, VA ,22042

1. Diagnosis of PAH classified by one of the following:
a. Idiopathic PAH (IPAH) or heritable PAH (HPAH).
b. PAH associated with connective tissue disease (CTD-APAH); these subjects will be capped at 30% of total planned enrollment and include:
    − Systemic sclerosis
    − Mixed CTD or overlap syndrome
    − Systemic lupus erythematosus
    − Other CTD established by American College of Rheumatology/ European Alliance of Associations for Rheumatology (ACR/EULAR) guidelines.

2. REVEAL Lite 2 Risk Score ≥ 5 OR NT-proBNP ≥ 300 ng/L OR PVR ≥ 800 dyne∙s/cm5

3. Evidence of an informed consent document, signed and dated by the subject, indicating that the subject has been informed of all pertinent aspects of the study prior to initiation of any subject-mandated procedures. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

4. Adult subjects aged 18 to 75 years (65 years for subjects receiving oral anticoagulants), inclusive, at the time of signing the ICF, prior to initiation of any study-specific activities/procedures.

5. Body mass index (BMI) ≥ 17 kg/m2 and ≤ 40 kg/m2.

1. Uncontrolled systemic hypertension as evidenced by systolic blood pressure > 160 mm Hg or diastolic blood pressure > 100 mm Hg during Screening visit after a period of rest.

2. WHO Pulmonary Hypertension Group 2 - 5.

3. Three or more of the following risk factors for left ventricular disease:
       a. BMI > 32 kg/m2
       b. Diagnosis of essential hypertension that is actively treated
       c. Diabetes mellitus
       d. Atrial fibrillation.

4. Untreated severe obstructive sleep apnea.

5. Body weight < 40 kg at Screening.

6. Initiation of an exercise program for cardiopulmonary rehabilitation within 12 weeks prior to Screening or planned during the study. Subjects who are already stable in the maintenance phase of an exercise program which will continue for the duration of the study are eligible.