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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Inhibikase Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2026-04-29

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Inhibikase Therapeutics, Inc.

External identifiers

EU CT number

2024-520218-23-00

ClinicalTrials.gov

NCT07365332

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety, Therapy, Pharmacodynamic

To evaluate the efficacy and safety of IKT-001 treatment versus placebo in addition to background PAH therapy in adults with WHO Group 1 PAH.

Conditions and MedDRA coding

Pulmonary Arterial Hypertension

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
2. 10. 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
3. 2. 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
4. 3. Men and women 18 and 75 years of age (inclusive) at the time of signing the ICF.
5. 4. Must have a BMI of ≥18.5 kg/m² and ≤35.0 kg/m² during screening.
6. 5. 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.
7. 6. 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.
8. 7. Anticipated to be able to perform the 6MWT according to American Thoracic Society Guidelines for the duration of the study.
9. 8. 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).
10. 9. NT-proBNP >300 ng/L during screening.
11. 11. 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.

Exclusion criteria 33

1. 1. Diagnosis of PAH WHO Groups 2, 3, 4, or 5.
2. 10. 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.
3. 11. Evidence of LVEF <45% (by Simpson’s biplane method) or evidence of impaired relaxation on screening echocardiogram by E/e’ >13.
4. 12. History of atrial fibrillation or atrial flutter.
5. 13. History of cerebrovascular accident, intracranial hemorrhage, or subdural hematoma at any time, or a fall associated with head trauma within 3 months of screening.
6. 14. 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.
7. 15. Acutely decompensated right heart failure within 30 days of screening, as per investigator assessment.
8. 16. Clinically significant ischemic, valvular, or constrictive heart disease, or heart failure with preserved ejection fraction, in the opinion of the investigator.
9. 17. History of pneumonectomy.
10. 18. Untreated or inadequately treated obstructive sleep apnea, in the opinion of the investigator.
11. 19. 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.
12. 2. Diagnosis of the following PAH Group 1 subtypes: • PAH associated with portal hypertension • Schistosomiasis-associated PAH • Pulmonary veno-occlusive disease
13. 20. 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).
14. 21. 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)
15. 22. 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).
16. 23. History of atrial septostomy within 180 days of screening.
17. 24. Current participation in another investigational clinical trial and/or receipt of any investigational medication within 90 days of screening.
18. 25. Previous randomization into this or another IKT-001 study.
19. 26. Any social, behavioral, or medical reason that would preclude completion of the study, in the judgement of the investigator.
20. 27. 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)
21. 28. Currently lactating, pregnant or planning on becoming pregnant during the study.
22. 29. Prior receipt of a solid organ transplant or stem cell transplant.
23. 3. 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
24. 30. 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).
25. 31. 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.
26. 4. Uncontrolled diabetes mellitus, defined as HbA1c ≥9.0%.
27. 5. 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
28. 6. History of restrictive, constrictive, or congestive cardiomyopathy.
29. 7. 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.
30. 8. Personal or family history of long QT syndrome or sudden cardiac death.
31. 9. Presence of a CardioMEMS device or any other implanted hemodynamic monitoring device.
32. 32. 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.
33. 33. 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. Part A: Change from baseline in PVR at Week 24
2. 2. Part B: Change from baseline in 6MWD at Week 24

Secondary endpoints 7

1. 1. Part A only: Change from baseline in 6MWD at Week 24
2. 2. Part B only: Change from baseline in PVR at Week 24
3. 3. Change from baseline in NT-proBNP concentrations at Week 24
4. 4. Time to all-cause death or the first occurrence of a clinical worsening event (time to clinical worsening)
5. 5. Proportion of participants who improve from baseline in WHO FC or maintain WHO FC II from baseline to Week 24
6. 6. Proportion of participants who maintain low or intermediate-low risk score or achieve a lower ESC/ERS 4 strata risk score at Week 24
7. 7. Change from baseline in HRQoL / EmPHasis-10 total score at Week 24

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Inhibikase Therapeutics Inc.

Sponsor organisation

Inhibikase Therapeutics Inc.

Address

3350 Riverwood Parkway Southeast # 1900

City

Atlanta

Postcode

30339-2066

Country

United States

Scientific contact point

Organisation

Inhibikase Therapeutics Inc.

Contact name

Chad Orevillo

Public contact point

Organisation

Inhibikase Therapeutics Inc.

Contact name

Chad Orevillo

Third parties 9

Locations

13 EU/EEA countries · 40 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 149 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications