Efficacy and Safety of IKT-001 in Adults with WHO Group 1 Pulmonary Arterial Hypertension: An Adaptive, Randomized, Double-Blind, Placebo-Controlled Trial

Trial ID: 2024-520218-23-00
Protocol: IKT-001-201
Sponsor: Inhibikase Therapeutics Inc.

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Diseases & Conditions

Pulmonary arterial hypertension

Objectives

The primary objective of this study is to evaluate the efficacy and safety of IKT-001 compared to a placebo in adult patients diagnosed with pulmonary arterial hypertension (WHO Group 1) receiving background therapy. The investigation assesses the therapeutic potential of IKT-001 as an add-on treatment. Additional clinical evaluations include pharmacodynamics and pharmacokinetics.

Participants

This study involves 396 participants diagnosed with pulmonary arterial hypertension. The study population consists of male and female adults between 18 and 75 years of age. Eligible individuals must have a documented diagnosis of WHO Group 1 PAH, including subtypes such as idiopathic, heritable, or drug/toxin-induced. Clinical requirements include an NT-proBNP level greater than 300 ng/L and a body mass index between 18.5 kg/m² and 35.0 kg/m². Participants must demonstrate specific hemodynamic profiles via right heart catheterization, including a pulmonary vascular resistance of ≥400 dyn·sec·cm⁻⁵ and a mean pulmonary arterial pressure of >20 mmHg. Subjects must be on stable background therapy with no more than three PAH-specific medications and must be capable of performing a six-minute walk test with a distance between 100 and 475 meters.

Plans and Procedures

This adaptive, 2-part, randomized, double-blind, placebo-controlled trial is designed to evaluate the efficacy and safety of IKT-001 compared to a placebo in adults diagnosed with pulmonary arterial hypertension. The study involves the administration of oral film-coated tablets as an addition to stable background therapy. The primary objectives include assessing the change from baseline in pulmonary vascular resistance during Part A and the change in six-minute walk distance during Part B at week 24. Secondary endpoints include changes in NT-proBNP concentrations, time to clinical worsening, and improvements in WHO functional class. The research methodology requires participants to undergo a screening period to confirm eligibility via right heart catheterization and six-minute walk test assessments. Following screening, participants will undergo scheduled visits to monitor clinical outcomes and safety through the 24-week treatment period. The trial is categorized as a phase 2b/3 study.

Treatment

The experimental medication, IkT-001Pro, is administered as a film-coated tablet. The active substance is butan-2-yl [1-methyl-4-[[4-[[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]carbamoyl]phenyl]methyl]piperazin-1-ium-1-yl]methyl carbonate methanesulfonate, which is delivered via the oral route. This study is designed to evaluate the efficacy and safety of the agent in adults with pulmonary arterial hypertension.

The placebo used in this trial is formulated to match 100 mg IKT-001 tablets. This comparator is administered in addition to background therapy to maintain the double-blind design of the study.

Efficacy

The efficacy of IKT-001 in patients with pulmonary arterial hypertension will be assessed through specific primary and secondary endpoints. In Part A of the trial, the primary endpoint is the change from baseline in pulmonary vascular resistance (PVR) at Week 24. In Part B, the primary endpoint is the change from baseline in the six-minute walk distance (6MWD) at Week 24. Secondary endpoints for Part A include the change from baseline in 6MWD at Week 24, while Part B focuses on the change from baseline in PVR at Week 24.

Additional secondary measures evaluated at Week 24 include:

Change from baseline in NT-proBNP concentrations.
Time to clinical worsening, defined as the time to all-cause death or the first occurrence of a clinical worsening event.
Proportion of participants demonstrating improvement from baseline in WHO functional class (WHO FC) or maintaining WHO FC II.
Proportion of participants maintaining a low or intermediate-low risk score or achieving a lower ESC/ERS 4 strata risk score.
Change from baseline in health-related quality of life (HRQoL) as measured by the EmPHasis-10 total score.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
If female and a WOCBP as defined in Section 7.2.1, must meet all the requirements below: • Agrees to use a contraceptive method that is highly effective (defined as having a failure rate of <1% per year as described in Section 7.2.2) from the time of first dose through 7 days after the last dose of study drug AND • Agrees not to donate eggs (ova, oocytes) for the purpose of reproduction from at least 14 days prior to dosing through the end of the study AND • Has negative pregnancy tests at screening and before the administration of the first dose of study drug
Documented diagnosis of WHO PAH Group 1 in any of the following subtypes: • Idiopathic PAH • Heritable PAH • Drug/toxin-induced PAH • PAH associated with CTD • PAH associated with simple, congenital systemic-to-pulmonary shunts ≥1 year following repair • HIV-associated PAH
Men and women 18 and 75 years of age (inclusive) at the time of signing the ICF.
Must have a BMI of ≥18.5 kg/m² and ≤35.0 kg/m² during screening.
Baseline RHC performed during the screening period documenting a PVR of ≥400 dyn·sec·cm⁻⁵, a PCWP or left ventricular end-diastolic pressure of ≤15 mmHg, and an mPAP of >20 mmHg.
On stable doses of background PAH therapy (≤3 PAH specific medications) including endothelin receptor antagonists, phosphodiesterase-5 inhibitors, prostacyclins, and soluble guanylate cyclase stimulators for ≥90 days before screening. Current use of sotatercept is not permitted in this study.
Anticipated to be able to perform the 6MWT according to American Thoracic Society Guidelines for the duration of the study.
6MWD ≥100 and ≤475 m repeated twice at screening (measured at least 4 hours but no longer than 1 week apart), with both values within 15% of each other (calculated from the highest value).
NT-proBNP >300 ng/L during screening.
If male with a pregnant partner or a partner who is a WOCBP, must agree to use a condom from the time of first dose through 7 days after the last dose of study drug.

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Exclusion Criteria

Diagnosis of PAH WHO Groups 2, 3, 4, or 5.
FVC <70% on PFT performed no more than 6 months before screening; or if FVC is 60% to 69%, must have a chest computed tomography scan within 12 months with no more than mild interstitial lung disease.
Evidence of LVEF <45% (by Simpson’s biplane method) or evidence of impaired relaxation on screening echocardiogram by E/e’ >13.
History of atrial fibrillation or atrial flutter.
History of cerebrovascular accident, intracranial hemorrhage, or subdural hematoma at any time, or a fall associated with head trauma within 3 months of screening.
Any symptomatic coronary disease event (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain) within 6 months of screening.
Acutely decompensated right heart failure within 30 days of screening, as per investigator assessment.
Clinically significant ischemic, valvular, or constrictive heart disease, or heart failure with preserved ejection fraction, in the opinion of the investigator.
History of pneumonectomy.
Untreated or inadequately treated obstructive sleep apnea, in the opinion of the investigator.
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 • HCV: a positive hepatitis C antibody test with detectable HCV 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.
Diagnosis of the following PAH Group 1 subtypes: • PAH associated with portal hypertension • Schistosomiasis-associated PAH • Pulmonary veno-occlusive disease
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 (eg, transfusion).
Received treatment with any of the following excluded medications: • Currently receiving strong CYP3A inducers or CYP3A inhibitors (except for topical administration) • Currently receiving or anticipated need to receive any anticoagulant (eg, heparins, vitamin K antagonists, direct oral anticoagulants, or direct thrombin inhibitors, with the exception of short-term, periprocedural use of anticoagulants (eg, heparin) administered during RHC, as deemed appropriate by the investigator) • Currently using sotatercept (Note: participants who previously received sotatercept may be considered if the last dose administered was >6 months before screening, participant had no significant bleeding events while on sotatercept, and the case is approved by the medical monitor prior to study entry)
Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days of 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 of screening.
Current participation in another investigational clinical trial and/or receipt of any investigational medication within 90 days of 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.
Any of the following clinical laboratory values: • ALT or AST levels >3× the ULN • Bilirubin levels >2× the ULN • ANC <1.2 ×10⁹ cells/L, hemoglobin <9 g/dL, hematocrit <30%, or platelets <75 × 10⁹ cells/L • Absolute eGFR <30 mL/min using creatinine or cystatin C as defined by the CKD-EPI equation (2021)
Currently lactating, pregnant or planning on becoming pregnant during the study.
Prior receipt of a solid organ transplant or stem cell transplant.
Diagnosis or history of any of the following substance-related conditions: • Methamphetamine-associated PAH • History of cocaine or methamphetamine (amphetamine-type stimulant) use within 24 months prior to screening defined by self-report, medical history, or positive drug screen in medical records • Any diagnosis of cocaine or methamphetamine use disorder (per medical record or self-report) within 24 months prior to screening
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 before screening 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.
Uncontrolled diabetes mellitus, defined as HbA1c ≥9.0%.
Any of the following BP-related values or abnormalities: • Uncontrolled systemic hypertension as evidenced by sitting systolic BP >160 mmHg or sitting diastolic BP >100 mmHg at screening after 5 minutes of rest • Baseline systolic BP <90 mmHg at screening • Syncope within 3 months before screening
History of restrictive, constrictive, or congestive cardiomyopathy.
ECG with 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.
History of clinically significant ophthalmologic disease that, in the opinion of the investigator, could be exacerbated by treatment with IKT-001, including but not limited to pre-existing macular edema, active glaucoma with poorly controlled intraocular pressure (defined as intraocular pressure >21 mmHg), or significant optic neuropathy.
Known hypersensitivity or allergy to the investigational medicinal product (IKT-001), its excipients (silicified microcrystalline cellulose, croscarmellose sodium, sodium stearyl fumarate, and Opadry II Green), or to process-related residuals (eg, butanol and formaldehyde).

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Austria	Not Yet Recruiting	01 Jun 2026	13
Belgium	Not Yet Recruiting	01 Jun 2026	5
Czechia	Not Yet Recruiting	01 Jun 2026	4
Denmark	Not Yet Recruiting	01 Jun 2026	2
France	Not Yet Recruiting	01 Jun 2026	8
Germany	Not Yet Recruiting	01 Jun 2026	11
Greece	Not Yet Recruiting	01 Jun 2026	6
Ireland	Not Yet Recruiting	01 Jun 2026	2
Italy	Not Yet Recruiting	01 Jun 2026	11
Latvia	Not Yet Recruiting	01 Jun 2026	5