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

I

Inhibikase Therapeutics

Status and phase

Begins enrollment this month
Phase 3

Conditions

Pulmonary Arterial Hypertension

Treatments

Drug: IKT-001
Drug: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT07365332
IKT-001-201

Details and patient eligibility

About

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.

Enrollment

486 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

486 participants in 2 patient groups, including a placebo group

IKT-001
Experimental group
Description:
IKT-001 tablets for PO administration
Treatment:
Drug: IKT-001
Placebo
Placebo Comparator group
Description:
Matching placebo to IKT-001 tablets for PO administration
Treatment:
Drug: Placebo

Trial contacts and locations

0

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Central trial contact

Medical Director, Inhibikase Therapeutics

Data sourced from clinicaltrials.gov

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