The investigational therapy BBT-401 effectively prevented ulcerative colitis symptoms in mice and rat models of the disease, and was shown to be safe and well-tolerated in healthy volunteers in a Phase 1 trial, its developer Bridge Biotherapeutics announced.
With these results, the company is set to launch a Phase 2 trial (NCT03800420) to evaluate the potential of BBT-401 in patients with ulcerative colitis. Currently recruiting participants for the first cohort, the trial is expected to start in February 2019.
The preclinical and Phase 1 clinical findings were discussed at the Crohn’s & Colitis Congress held Feb. 7 to 9 in Las Vegas, NV.
The session, “BBT-401 Is a Selective Pellino-1 Protein-Protein Interaction Inhibitor in Clinical Development Targeting a First-in-Class Drug for UC Treatment,” was presented by Gwanghee Lee, PhD, senior vice president of translational research at Bridge Biotherapeutics.
BBT-401 is a potent and selective inhibitor of Pellino-1 protein, and was initially discovered by researchers at Sungkyunkwan University and Korea Research Institute of Chemical Technology. The compound was licensed to Bridge Biotherapeutics in 2015.
By blocking Pellino-1 activity, BBT-401 prevents several important proteins, including MyD88 and NF-KB, from promoting the inflammatory process implicated in ulcerative colitis. The agent can also prevent the release of pro-inflammatory signaling molecules, including TNF-alpha and interleukin-6, among others.
“Our team aims to develop the drug candidate as the first-in-class drug for ulcerative colitis as fast as possible to bring this novel compound to patients as a new treatment option, proving strong anti-inflammatory efficacy in active ulcerative colitis patients,” Lee said in a press release.
Increasing doses of BBT-401 — administrated daily to mice for 10 days and to rats for 14 days with induced ulcerative colitis — was shown to reduce disease symptoms significantly. Oral administration showed no systemic exposure, demonstrating the colon-targeted effect.
Researchers have also tested the safety and tolerability of BBT-401 in 80 healthy volunteers in a Phase 1 trial (NCT03482648). Participants were randomized to take a single capsule with one of seven dose levels of BBT-401, one of three ascending doses of BBT-401 for seven consecutive days, or a matching placebo.
The data showed BBT-401 is not detectable in the blood, confirming no systemic exposure and its potentially exclusive activity on intestinal membranes.
The treatment was generally found to be safe and well-tolerated, with most side effects reported as mild in severity. The most common side effects were diarrhea — experienced by 20% of the participants treated with BBT-401, and by 5% of the placebo group — and mild headaches.
Bridge Biotherapeutics’ Phase 2 trial (NCT03800420) will explore the safety, tolerability, and efficacy of ascending doses of BBT-401. Researchers will evaluate the impact of the treatment on disease activity and levels of important inflammation biomarkers.
Up to 16 patients will be included per dose group and randomized to receive the active agent or a placebo for eight weeks. Dosing of the first group will start at a pre-established level, while the regimens of the second and third groups will be determined based on the previous group’s results.
Three study sites in California, Maryland, and North Carolina are currently enrolling participants. Bridge Biotherapeutics expects to add seven other study sites to the trial, according to a press release. Clinical data from the first group is anticipated during the second half of 2019.
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