France’s National Agency for the Safety of Medicine and Health Products (ANSM) has cleared the inclusion of French study sites for Abivax‘s new Phase 2b clinical trial, intended to evaluate several oral doses of its lead investigational therapy ABX464 for moderate-to-severe ulcerative colitis (UC).
With the decision by the ANSM, the clinical trial (NCT03760003) for ABX464 is now fully approved in 15 countries and will run in nearly 150 study sites.
Patient recruiting is ongoing. More information about trial contacts is available here.
Top-line data from the study, which aims to enroll 232 patients with moderate-to-severe UC, is expected at the end of 2020.
“We are very pleased with ANSM giving us the green light for the continued clinical development of this promising compound in France,” Hartmut J. Ehrlich, MD, CEO of Abivax, said in a press release.
The company recently presented promising results from the open-label extension study of ABX464 (NCT03368118). After one year of maintenance therapy with daily 50 mg capsules of ABX464, 75% of the evaluated patients — 12 out of 19 — were in clinical remission, meaning they are free of any symptoms of the disease. These patients had moderate-to-severe, active UC, and had previously failed other treatments, including immunomodulators, anti-TNF biologics, Entyvio, or corticosteroids.
“So far, our study results with ABX464 are truly remarkable. With currently available treatments, including biologics, typically only 10-25% of the patients achieve clinical remission after 2 months of induction, and half of the responders stop responding after six to twelve months, so there is a large unmet need for effective ulcerative colitis therapies,” said Jean-Marc Steens, MD, Abivax’s chief medical officer.
The Phase 2b study, ABX464-103, will evaluate the efficacy and safety of three oral doses of ABX464 — 25 mg, 50 mg, and 100 mg — as compared with placebo. The therapy will be given daily to the trial’s participants, all of whom have moderate-to-severe UC and had a poor response or were intolerant to prior treatments.
A total of 232 individuals are expected to enroll. Participants will be randomly assigned to one of four groups, one for each dose of ABX464, or a matching placebo. The study includes an initial, blinded treatment spanning 16 weeks — the induction phase — followed by an open-label maintenance study (NCT04023396), for an overall period of 48 weeks.
The primary efficacy measure will be a reduction in the modified Mayo Score, a tool for assessing disease activity in UC, at eight weeks. Secondary measures include clinical remission, improvement in endoscopy findings, and levels of fecal calprotectin, which is a biomarker for intestinal inflammation.
“With the ABX464-103 study (Phase 2b), we are planning to confirm these excellent outcomes in a statistically relevant number of patients and, at the same time, evaluate different doses of ABX464 to define the optimal dose for subsequent Phase 3 testing. We are looking forward to advancing this exciting program with ABX464, a novel, first-in-class molecule with an innovative mode of action that could make a difference in treating patients suffering from this emaciating inflammatory disease,” Ehrlich said.
ABX464 is an investigational, small molecule with a new mechanism of action. It works by promoting the production of a small microRNA (miRNA-124), which was seen to be safe and have strong anti-inflammatory activity in preclinical studies.
“This is a debilitating disease that greatly affects patients’ quality of life and requires expensive and cumbersome therapies,” Steens said. “The innovative mechanism of action of ABX464 and data from this trial represent a promising new potential approach to the treatment of ulcerative colitis that could provide these patients with an easily administered, once-daily oral, long-term therapeutic management option.”
A Phase 2a study (NCT03905109) to test ABX464 for the treatment of severe, active Crohn’s disease is expected to start in the first quarter of 2020, Abivax also announced.