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

Официальное название

An Adaptive, 2-Part, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of IKT-001 in Pulmonary Arterial Hypertension (PAH)

Обзор

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.

Вмешательства

• Препарат IKT-001
  IKT-001 tablets for PO administration
• Препарат Placebo
  Placebo to IKT-001 tablets for PO administration

Первичные конечные точки

• [Part A] To evaluate the effect on Pulmonary Vascular Resistance (PVR) in participants with WHO Group 1 PAH treated with IKT-001 compared to placebo [Срок оценки: Baseline to Week 24]
• [Part B] To characterize the effects of IKT-001 on symptoms and characteristics of Pulmonary Arterial Hypertension compared to placebo [Срок оценки: Baseline to Week 24]

Вторичные конечные точки (2)

• To characterize the effects of IKT-001 on WHO Functional Class [Срок оценки: Baseline up to Week 48]
• To characterize the effects of IKT-001 on time to clinical worsening [Срок оценки: Baseline up to Week 48]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 2 центра

• Norton Healthcare — Louisville
• Tufts Medical Center — Boston

Идентификаторы

NCT: NCT07365332 · IKT-001-201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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