An Adaptive Program of IKT-001 in Pulmonary Arterial Hypertension (PAH)
Purpose
This is an adaptive, 2-part, randomized, multicenter, double-blind, placebo-controlled, parallel-group study designed to evaluate the efficacy and safety of IKT-001 in adult participants with WHO Group 1 PAH.
Condition
- Pulmonary Arterial Hypertension
Eligibility
- Eligible Ages
- Between 18 Years and 75 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Documented diagnosis of WHO PAH Group 1 in any of the following subtypes: - Idiopathic PAH - Heritable PAH - Drug/toxin-induced PAH - PAH associated with connective tissue disease (CTD) - PAH associated with simple, congenital systemic-to-pulmonary shunts at least 1 year following repair - Men and women 18 and 75 years of age (inclusive) - Must have a body mass index (BMI) of ≥18.5 kg/m^2 and ≤35.0 kg/m^2 at screening. - Baseline RHC performed during the Screening Period documenting a PVR of ≥ 400 dyn/sec/cm^5 ; pulmonary capillary wedge pressure (PCWP) ≤15 mmHg and mean pulmonary artery pressure (mPAP) >20 mmHg. PVR enrichment criteria to ensure population baseline PVR >700 dynes/sec/cm^5 - On stable doses of background PAH therapy including endothelin receptor antagonists, phosphodiesterase-5 inhibitors, prostacyclins, and soluble guanylate cyclase stimulators for ≥90 days prior to screening. Current use of sotatercept is not permitted. - 6MWD ≥ 100 and ≤ 475 m
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.
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Adaptive, 2-part, randomized, multicenter, double-blind, placebo-controlled, parallel-group study
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental IKT-001 |
IKT-001 tablets for PO administration |
|
|
Placebo Comparator Placebo |
Matching placebo to IKT-001 tablets for PO administration |
|
Recruiting Locations
Norton Healthcare
Louisville, Kentucky 40202
Louisville, Kentucky 40202
Tufts Medical Center
Boston, Massachusetts 02111
Boston, Massachusetts 02111
More Details
- Status
- Recruiting
- Sponsor
- Inhibikase Therapeutics