First Patient Enrolled in IMPROVE-PAH Phase 3 Study

Key takeaways:

• First patient enrolled in the global, adaptive, two-part Phase 3 IMPROVE-PAH trial of IKT-001 in PAH
• Part A primary endpoint: change in pulmonary vascular resistance at Week 24; Part B: change in 6-minute walk distance at Week 24
• Trial includes dose titration, potential sample size adjustment, and is described by the sponsor as supported by FDA feedback on study design

In a sponsor announcement, Inhibikase Therapeutics reported that the first patient has been enrolled in the global Phase 3 IMPROVE-PAH trial evaluating IKT-001 for pulmonary arterial hypertension (PAH). The company indicated that the study has been designed as a single, adaptive, two-part pivotal program intended to streamline development and potentially support a future NDA submission.

IMPROVE-PAH is structured as a sequential, two-part Phase 3 trial with distinct primary endpoints in each portion. Part A is described as a randomized, double-blind, placebo-controlled study enrolling approximately 140 patients, with the primary endpoint defined as change in pulmonary vascular resistance (PVR) at Week 24. Part B is planned to follow using a similar trial framework, enrolling approximately 346 patients, with the primary endpoint defined as change in 6-minute walk distance (6MWD) at Week 24.

The company characterized the design as adaptive and continuous, with Part B expected to begin after the final patient is enrolled in Part A, without a pause between phases. The sequencing reflects an initial focus on hemodynamic outcomes in Part A, followed by functional outcomes in Part B.

According to the sponsor, the protocol incorporates several adaptive and operational features. These include a 12-week dose-titration period intended to optimize dosing at the individual patient level, as well as the option to adjust the Part B sample size based on data emerging from Part A. Enrollment is expected to proceed seamlessly across both parts of the study.

Operationally, IMPROVE-PAH is described as a global trial expected to involve up to approximately 180 sites. The announcement emphasized the overall scale and international scope of the program but did not provide detailed information on geographic distribution, site activation timelines, or enrollment projections.

IKT-001, the investigational therapy, is described by the company as an oral prodrug of imatinib. The prodrug approach is intended to mitigate gastrointestinal side effects associated with imatinib, which has an established clinical history spanning more than two decades. The company also stated that written feedback from the U.S. Food and Drug Administration supported the revised pivotal trial design.

The announcement did not include detailed eligibility criteria, background therapy requirements, or site-level participation information. Overall, the update focused on the structure of the IMPROVE-PAH trial, including its adaptive design, defined endpoints, and operational approach, while providing limited detail on patient selection or clinical implementation.