Canada has become the first country to fully authorize a Phase 2b clinical trial that will explore Abivax‘s lead candidate ABX464 in patients with ulcerative colitis, the company announced.
ABX464 was granted complete regulatory and ethics approval in Canada, and the first patient is expected to be enrolled in the trial in the second quarter of this year, Hartmut J. Ehrlich, MD, CEO of Abivax, said in a press release.
In addition to Canada, the Phase 2b trial (NCT03760003) is expected to be largely conducted in Europe, with up to 150 sites across more than 15 countries.
It will enroll approximately 232 patients with moderate to severe ulcerative colitis, who will be randomized into four groups. Three groups will receive escalating doses of once-daily oral ABX464 — 25 mg, 50 mg, or 100 mg per day — and the last group will receive a placebo for control.
Participants will receive the treatment for 16 weeks. After completion of the study, patients will have the opportunity to continue treatment with ABX464o in an open-label maintenance study.
Top-line results from this trial are expected to be presented by the end of 2020.
The primary goal of the trial is to assess changes in modified Mayo Score (which measures ulcerative colitis disease activity) at eight weeks compared with before starting the treatment. Researchers will also evaluate the impact of the treatment on different disease-associated features, such as endoscopic improvements, levels of the fecal biomarker calprotectin, and patients’ clinical remission overall.
“We look forward to initiation of this Phase 2b trial in which we hope to confirm the exciting findings from the Phase 2a trial … as well as determine the optimal dose for Phase 3 pivotal studies,” said Séverine Vermeire, MD, PhD, a professor at the Katholieke Universiteit Leuven in Belgium.
ABX464 is a small molecule that was first developed to reduce viral load in HIV-positive people. However, it also showed strong and long-lasting anti-inflammatory properties in a mouse model for colon inflammation. It works by increasing the levels of an active long non-coding RNA molecule that can, in turn, induce the production of another anti-inflammatory molecule called miR-124.
In 2018, Abivax reported top-line safety and efficacy results from a Phase 2a trial (NCT03093259), which showed that 50 mg daily of oral ABX464 in patients with moderate to severe ulcerative colitis was safe and well-tolerated, and was associated with a significant reduction in disease activity and hallmarks of inflammation.
“ABX464’s novel mechanism of action … and the excellent results from our Phase 2a induction and ongoing maintenance study in ulcerative colitis patients has further validated our decision to accelerate the development of this highly differentiated, oral, first-in-class therapeutic candidate,” Erhlich said.
Results from the Phase 2a trial, which includes data from patients who are already in the second year of maintenance treatment with ABX464, will be discussed at an oral presentation on May 21 during Digestive Disease Week in San Diego.
Based on the positive results of the Phase 2a trial, Abivax is now preparing to launch additional studies to further assess the potential of ABX464 in patients with Crohn’s disease and rheumatoid arthritis.
It has already submitted a request to regulatory authorities in several countries for approval of a Phase 2a trial in rheumatoid arthritis, and expects to submit applications to launch a trial in Crohn’s disease in the coming weeks, Ehrlich said.