Authorised Phase II and Phase III (Integrated) Pulmonary Arterial Hypertension

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

EU CTIS ID: 2024-520218-23-00

What this study is testing

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.

Phase II and Phase III (Integrated)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
9. NT-proBNP >300 ng/L during screening.
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.
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
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
3. Men and women 18 and 75 years of age (inclusive) at the time of signing the ICF.

You likely can't join if

1. Diagnosis of PAH WHO Groups 2, 3, 4, or 5.
18. Untreated or inadequately treated obstructive sleep apnea, in the opinion of the investigator.
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.
2. Diagnosis of the following PAH Group 1 subtypes: • PAH associated with portal hypertension • Schistosomiasis-associated PAH • Pulmonary veno-occlusive disease
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).
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)

See the full eligibility criteria

Who can join

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

What rules you out

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

The study team makes the final eligibility decision.

Where it's taking place

Chile
Canada
Turkey
Israel
Thailand
New Zealand
Mexico
Singapore
United States
China
Brazil
Australia
Switzerland
Korea, Republic of
Argentina
Japan
Colombia
United Kingdom

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Chile; Canada; Turkey; Israel; Thailand; New Zealand and 12 more location(s). Enter your location above to see the nearest site and check your eligibility.

Explore other conditions

Obesity Type 2 diabetes Type 1 diabetes Prediabetes Weight loss Metabolic syndrome High cholesterol High triglycerides High blood pressure PCOS Hypothyroidism Thyroid disease Gout Fatty liver disease (NAFLD/NASH)Heart failure Coronary artery disease

BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.