A Phase 3 trial of edasalonexent, an oral disease-modifying treatment candidate, is enrolling boys with Duchenne muscular dystrophy (DMD) at multiple sites in the U.S. and will soon open sites worldwide, according to Catabasis Pharmaceuticals.
Nine sites across the U.S. are now enrolling participants for this one-year, randomized, double-blind, placebo-controlled study named PolarisDMD (NCT03703882). More information on locations and contacts can be found here. At least 10 more sites are expected to open shortly.
Catabasis is also hoping to open trial sites in Canada this month. Sites in Europe, Australia, and Israel are expected to open in the first quarter of 2019, pending regulatory approval. In total, about 40 trial sites worldwide are planned for PolarisDMD, with enrollment anticipated to conclude in 2019.
Perry Esler, executive director of Jesse’s Journey, focused on funding research on DMD, said in a press release that the charity is “very pleased that the PolarisDMD trial for edasalonexent will enroll patients at sites in Canada,” adding that Jesse’s Journey is “very supportive” of treatments such as edasalonexent “that have the potential to benefit all boys and men affected by Duchenne, and we know that these trials are a high priority for families.”
Approximately 125 participants ages 4 to 7 years, regardless of mutation type, who have not been on steroids for at least six months, will be included. Patients on a stable dose of Sarepta‘s Exondys 51 (eteplirsen) may be eligible.
Edasalonexent (CAT-1004) is a small molecule that inhibits a protein called NF-kB, which plays an essential role in skeletal and cardiac muscle. This blocks a crucial pathway driving DMD disease progression and muscle fiber breakdown.
PolarisDMD will assess the efficacy and safety of edasalonexent in boys with DMD. The patients will be able to choose the easiest-to-swallow oral capsule of edasalonexent from two available sizes. Two boys will take edasalonexent at 100 mg/kg per day for each patient on placebo. After 12 months, researchers plan for all the boys to take edasalonexent in an open-label extension study.
The primary efficacy goal is changes in the North Star Ambulatory Assessment score — a tool to measure motor abilities in children with DMD — after one year of treatment with edasalonexent compared with placebo. Secondary goals include three age-appropriate function tests: time to stand, four-stair climb, and 10-meter walk/run. Evaluations of growth, and of cardiac and bone health will also be conducted.
Trial design was guided by input from regulators, treating physicians, patient organizations, and families of boys with DMD. Catabasis expects top-line results in the second quarter of 2020. PolarisDMD is intended to support an application for commercial registration of the investigational medication.
“We are very excited to be screening and dosing patients in our Phase 3 PolarisDMD trial as we believe edasalonexent has tremendous potential for all those affected by Duchenne, regardless of mutation type and from the time of diagnosis throughout their lifespan,” said Joanne Donovan, MD, PhD, Catabasis’ chief medical officer
“We are monitoring bone and heart health in the PolarisDMD trial, in addition to the assessments of skeletal muscle function, as we see these as important potential differentiating benefits of edasalonexent,” Donovan added. She also mentioned the “extensive inbound interest” Catabasis received from families, who are being referred to the enrolling trial sites.
PolarisDMD is intended to confirm the positive results of the MoveDMD Phase 1/2 trial (NCT02439216) and its open-label extension. In MoveDMD, treatment with edasalonexent preserved muscle function and markedly slowed disease progression through 72 weeks compared with controls. Other improvements found in MoveDMD included reduced inflammation and fat content in the lower leg and quadriceps in boys receiving edasalonexent.
According to Catabasis, data from preclinical studies and from MoveDMD suggest that treatment with edasalonexent could benefit the skeletal muscle, diaphragm and heart. The investigational therapy has been well-tolerated in more than 50 patient-years — a measure of incidence obtained by multiplying the number of people at risk per time — with no safety issues observed.