Phase 2 trial of TX45 for PH-HFpEF beginning to enroll patients
Treatment aims to lower blood pressure by relaxing and widening vessels
A Phase 2 clinical trial of TX45, Tectonic Therapeutic’s investigational therapy for pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF), has begun enrolling eligible patients.
The Phase 2 study, called APEX (NCT06616974), is expected to recruit up to 180 adults with PH-HFpEF, ages 18 to 80. To be eligible, participants must not be able to conceive children and must be able to walk between 100 to 450 meters (328 to 1,476 feet) in six minutes. Other criteria include being on stable doses of therapies for heart failure or cardiovascular disease.
Recruitment into the APEX study has begun at a site in Moldova. Sites also are expected to open in the U.S., Armenia, Australia, Bulgaria, Georgia, Germany, New Zealand, Poland, Spain, and Turkey.
Phase 2 PH-HFpEF clinical trial will have 2 treatment groups, 1 placebo group
All enrolled will be given subcutaneous (under-the-skin) injections every two weeks, and they will be divided into three groups. In one group, every injection given will be a placebo. In a second group, injections will contain TX45 at a 300 mg dose. In a third group, injections will alternate between TX45 and a placebo. Essentially, this group will be given TX45 injections once monthly instead of every other week, but with an injection schedule matching the other groups so the change won’t be evident.
The selection of doses for Phase 2 testing was based on positive results from the Phase 1a part of an ongoing Phase 1 study. The trial’s Phase 1a part tested the safety and pharmacological profile of TX45 in healthy volunteers.
“Favorable Phase 1a results allowed us to confidently move ahead with our APEX Phase 2 clinical trial,” Alise Reicin, MD, president and CEO of Tectonic, said in a company press release.
In the healthy volunteers, safety data were positive: no severe side effects related to TX45 were documented. The most common side effect was orthostatic tachycardia (an increase in heart rate while standing), which was temporary and did not lead to changes in blood pressure.
Pharmacological data suggest that the half-life of the therapy is about two to three weeks. Half-life refers to the time it takes for half of the medication to be processed out of the body. Phase 1a trial data also indicated that TX45 led to increases in renal plasma flow, a measure of how much blood is being pumped through the kidneys. Results indicated an average increase in this measure of up to 42%.
Collectively, these pharmacological data supported the selection of 300 mg every other week or every four weeks for testing in the APEX study.
PH-HFpEF patients currently lack an approved disease treatment
PH-HFpEF is a form of pulmonary hypertension that develops when the heart is able to pump blood in a near normal way, but heart muscle is unusually stiff. As a consequence, the left ventricle, which normally pumps oxygen-rich blood out to the body, can’t keep up with the body’s demands, and high blood pressure develops in the vessels that carry blood to the lungs. Currently, there are no approved treatments for PH-HFpEF.
TX45 contains a version of relaxin, a naturally occurring protein that can reduce blood pressure by prompting blood vessels to relax and widen. Among its functions, the relaxin hormone is normally produced during pregnancy to help ensure that enough blood is flowing to support a developing fetus.
The ongoing Phase 1b part of the Phase 1 trial is exploring the effects of a single dose of TX45 on blood flow measurements (hemodynamics) in people with PH-HFpEF. Results are expected in the first half of 2025, while results of the APEX study are anticipated in 2026.
“We are excited to build on this positive Phase 1a study with the ongoing single-dose Phase 1b hemodynamic trial and the APEX Phase 2 clinical trial,” said Marcella Ruddy, MD, Tectonic’s chief medical officer. “Results from these trials are expected to define the therapeutic effects of TX45 and enable us to understand its potential role in the treatment of patients with PH-HFpEF.”
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