An Adaptive Program of IKT-001 in Pulmonary Arterial Hypertension (PAH)

Exclusion Criteria

• •Diagnosis of PAH WHO Groups 2, 3, 4, or 5.
• •Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency virus (HIV)-associated PAH, PAH associated with portal hypertension, schistosomiasis-associated PAH, and pulmonary veno-occlusive disease.
• •Any of the following blood pressure-related values or abnormalities: Uncontrolled systemic hypertension as evidenced by sitting systolic BP \>160 mmHg or sitting diastolic BP \>100 mmHg at screening, Baseline systolic BP \<90 mmHg at screening, Syncope within 3 months prior to screening
• •History of restrictive, constrictive, or congestive cardiomyopathy.
• •ECG with Fridericia's corrected QT interval (QTcF) ≥ 450 msec in males or ≥ 470 msec in females at screening or ≥500 msec in the presence of a right bundle branch block.
• •Personal or family history of long QT syndrome or sudden cardiac death.
• •Presence of a CardioMEMS device or any other implanted hemodynamic monitoring device.
• •Forced vital capacity (FVC) \<70 percent on pulmonary function test (PFT) performed no more than 6 months prior to screening; or if FVC is 60 percent to 69 percent, must have a chest computed tomography scan within 12 months with no more than mild interstitial lung disease.
• •History of atrial fibrillation or atrial flutter.
• •History of cerebrovascular accident, intracranial hemorrhage, or subdural hematoma at anytime, or a fall associated with head trauma within 3 months of screening.
• •Acutely decompensated right heart failure within 30 days prior to screening, as per investigator assessment.
• •Clinically significant ischemic, valvular, constrictive heart disease, or heart failure with preserved ejection fraction in the opinion of the investigator.
• •History of pneumonectomy.
• •Untreated or inadequately treated (in the opinion of the investigator) obstructive sleep apnea.
• •Acute or chronic hepatitis B or C infection, defined as:
• •* Hepatitis B virus: a positive hepatitis B surface antigen test or a positive hepatitis B core antibody test with detectable DNA
• •* Hepatitis C virus (HCV): a positive hepatitis C antibody test with detectable HCV ribonucleic acid (RNA).Participants with a positive hepatitis C antibody test, but no detectable HCV RNA who completed treatment with direct-acting antivirals may be considered after discussion with the medical monitor.
• •History of or currently diagnosed with a bleeding disorder, including but not limited to hemophilia, von Willebrand disease, thrombocytopenia, or significant bleeding history defined as any bleeding event requiring medical intervention.
• •Received treatment with any of the following excluded medications:
• •* Currently receiving strong cytochrome P450 (CYP) 3A inducers or CYP3A inhibitors (except for topical administration)
• •* Currently receiving or anticipated need to receive any anticoagulant (e.g., heparins, vitamin K antagonists, direct oral anticoagulants, or direct thrombin inhibitors).
• •* Current use of sotatercept. Note: participants who previously received sotatercept may be considered if the last dose administered was \>6 months prior to screening, participant had no significant bleeding events while on sotatercept.
• •Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to screening or planned initiation during the study (participants who are stable in the maintenance phase of a program and who will continue for the duration of the study are eligible).
• •History of atrial septostomy within 180 days prior to screening.
• •Current participation in another investigational clinical trial and/or receipt of any investigational medication within 90 days prior to screening.
• •Previous randomization into this or another IKT-001 study.
• •Any social, behavioral, or medical reason that would preclude completion of the study, in the judgement of the investigator.
• •Currently lactating, pregnant or planning on becoming pregnant during the study.
• •Prior receipt of a solid organ transplant or stem cell transplant.
• •Planned surgery that would require any study drug interruption or interfere with study assessments during the study (minor procedures may be allowed in consultation with the medical monitor).
• •Malignancy within the last 5 years prior to consent except completely treated non-metastatic-basal cell, squamous cell, in situ cervical cancer, and clinically localized National Comprehensive Cancer Network very low to low risk prostate cancer under active surveillance.