First patient enrolled in Phase 3 trial of PAH treatment IKT-001
2-part trial aimed at accelerating therapy's regulatory approval path
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The first participant has been enrolled in a two-part Phase 3 clinical trial testing IKT-001, Inhibikase Therapeutics’ experimental formulation of imatinib, in people with pulmonary arterial hypertension (PAH).
The Phase 3 IMPROVE-PAH trial (NCT07365332) is expected to enroll nearly 500 adults with various forms of PAH, ages 18 to 75, who are on stable treatment with available PAH therapies. The trial will be conducted at approximately 180 sites worldwide and is designed to be pivotal — meaning that if results are positive, Inhibikase hopes to use the findings as a basis to apply for regulatory approvals.
“Enrollment of the first patient in our IMPROVE-PAH trial is a major milestone for Inhibikase, and the result of many months of work to optimize the IKT-001 study plan to permit a single pivotal global study and significantly accelerate the timeline to potential [new drug application] filing,” Mark Iwicki, CEO of Inhibikase, said in a company press release.
The first part of IMPROVE-PAH will test IKT-001 against a placebo in approximately 140 people with PAH. The main goal is to test how the therapy affects pulmonary vascular resistance (a measure of how difficult it is for blood to flow from the heart to the lungs) after about six months.
As soon as the trial’s first part finishes enrolling, the second part will start. That part will also compare IKT-001 against a placebo for six months, but the main goal is to test if the therapy can improve six-minute walk distance (6MWD), a standard measure of exercise capacity. That second part is expected to enroll approximately 346 patients, but per the trial’s design, this number may be adjusted based on findings from the first part.
Measuring ‘the outcomes that matter most’
“The Phase 3 IMPROVE-PAH study will help evaluate both hemodynamic [blood flow measurement] and functional improvements, as well as key measures of disease progression, such as time to clinical worsening,” said Harrison Farber, MD, a pulmonologist at Tufts Medical Center.
Both parts of the study will include a 12-week dose-titration phase, meaning that for the first three months, the dose of the experimental drug will be gradually adjusted to find the highest dose each participant can tolerate without unacceptable side effects. The U.S. Food and Drug Administration (FDA) trial design has supported the trial design. The study is expected to end in 2029.
“The IMPROVE-PAH trial represents a meaningful step forward because the trial is designed to capture the outcomes that matter most to patients and clinicians alike,” said J. Wesley McConnell, MD, director of the Norton Pulmonary Specialists Pulmonary Hypertension Center in Louisville, Kentucky. “I am proud to be part of this program and optimistic about what it could mean for the future of PAH care.”
PAH is marked by abnormal cell growth in the vessels that carry blood from the heart through the lungs, leading to high pressure in these vessels and, consequently, strain on the heart. Imatinib, originally developed as an anticancer agent, is a drug that blocks cell growth. Novartis developed an oral formulation, imatinib mesylate, as a potential PAH treatment. In clinical trials, that formulation was shown to improve exercise capacity for PAH patients, but it also caused substantial safety issues, leading Novartis to discontinue its development.
IKT-001 is an inactive precursor molecule that’s converted into imatinib once inside the body. Inhibikase is developing the therapy with the aim of offering similar benefits to Novartis’ prior candidate, but with a more acceptable safety profile.
“Despite the availability of multiple therapies, many patients with PAH continue to experience disease progression, so I am always excited about the potential for a novel antiproliferative [anti-cell growth] agent for the treatment of PAH,” Farber said.
