Aytu Begins Phase 3 Trial of AR101, Possible Vascular EDS Treatment
Aytu BioPharma has launched a Phase 3 trial, called PREVEnt, to evaluate its experimental oral treatment AR101 (enzastaurin) in people with COL3A1-positive vascular Ehlers-Danlos Syndrome — vascular EDS or vEDS — a severe subtype of the disease.
“We are excited about the progression of this global clinical trial evaluating a novel pathway for the treatment of VEDS, a devastating rare disease with massive unmet need,” Josh Disbrow, CEO of Aytu, said in a company press release.
“The PREVEnt trial is global in nature with an anticipated 30+ sites across the US and Europe. We have received an FDA safe to proceed letter, and in Europe have garnered regulatory authority and ethics commission approvals to begin clinical work in multiple countries,” Disbrow said, adding, “We anticipate additional country-specific approvals in the coming months.”
The clinical study — which the company calls Prevention of Rupture with Enzastaurin in Vascular Ehlers-Danlos Syndrome (NCT05463679) — is not yet recruiting participants; dosing is expected to start early next year. Additional information is available through a trial website.
“We are so grateful to all the clinical trial sites for their efforts in aiding our study start up with the aim of dosing a first patient by early 2023,” said Topher Brooke, Aytu’s executive vice president of rare disease development.
“In coordination with trial sites and patient advocacy organizations in the US and Europe, we plan to make it as easy as possible to participate in the PREVEnt trial, including allowing patients to continue any VEDS-related therapies they are currently taking for the duration of the study,” Brooke said.
PREVEnt is expected to enroll approximately 260 adults with vEDS, ages 18 to 60, who have a confirmed mutation in the COL3A1 gene. The study may later open to patients as young as age 12, depending on the results of interim analyses.
To be eligible, participants must not have had any vascular events — tearing of blood vessels or structural alterations that characterize vEDS, including rupture, dissection, pseudoaneurysm, carotid-cavernous sinus fistula, or aneurysm — in the three months before entering the trial. Participants also must agree to use contraception while enrolled in the study.
The trial is double-blind, meaning that neither researchers nor participants will know which patients are receiving the placebo and which the potential new vascular EDS treatment. Each patient will be randomly assigned to take AR101, at a dose of 125 mg, or the placebo, once daily.
The study’s main goal is to evaluate the impact of treatment on vascular events after 30 months (2.5 years) of treatment. Safety and tolerability outcomes also will be explored.
AR101 is designed to block the activity of a protein called PKC beta. According to Aytu, the experimental treatment prevented death due to blood vessel rupture in a mouse model of vEDS. The therapy has been granted orphan drug designations for vEDS in the U.S. and Europe.