Theravance Biopharma announced that the first patient has been dosed in a Phase 2b/3 study to test the efficacy and safety of its candidate oral drug TD-1473 for the treatment of moderate to severe active ulcerative colitis.
The Phase 2b/3 clinical trial (NCT03758443) is still recruiting participants.
TD-1473 is a novel oral drug that selectively inhibits the Janus kinase (JAK) family of enzymes. The drug blocks JAK signaling pathways involved in the spread of inflammatory signals, namely those triggered by immune messengers, referred to as cytokines.
Contrary to other JAK inhibitors approved for IBD and other illnesses, TD-1473 was designed to act predominantly in the gastrointestinal tract, thus overcoming potential side effects due to a generalized, or systemic, exposure to the drug.
An early exploratory study sponsored by Theravance has yielded encouraging results for the use of TD-1473 for people with ulcerative colitis.
Now, the company initiated a Phase 2b/3 clinical trial (NCT03758443) to evaluate the efficacy, safety and dose tolerability of TD-1473, given as an initial therapy and a maintenance treatment for moderate to severe active ulcerative colitis.
The study is a randomized, double-blind, placebo-control trial being conducted at centers across the U.S.
In the first part of the study (phase 2b induction), patients will be randomly assigned to one of four groups, one having placebo and the other three each having a different dose of TD-1473 per day over eight weeks.
Based on the efficacy and safety results obtained in this part, one or more doses of TD-1473 will be selected for the second part of the study (phase 3 induction), meant to evaluate the target doses as a primary treatment of eight weeks.
The primary outcome measure of efficacy will be the change in clinical remission rates in the TD-1473 group compared to the placebo group at the end of this treatment.
Remission will be assessed by the Mayo score components evaluating rectal bleeding, stool frequency, and endoscopy findings.
Patients who achieve positive responses either in the first or the second portion of the study will move to its third part (phase 3 maintenance).
The participants in this group will be randomized to receive placebo or one of two doses of TD-1473 over 44 weeks. The main goal is to assess the proportion of those who enter clinical remission at the end of the treatment period, in addition to determining safety and drug tolerance.
The study is currently recruiting and the first patient has been dosed.
It marks another step toward the clinical development of TD-1473 for IBD, the launch of a Phase 2 study (NCT03635112) testing the same drug for patients with Crohn’s disease.
In February 2018, Theravance entered a global partnership with Janssen for the development and commercialization of TD-1473 for the treatment of IBD.
“The breadth of our TD-1473 clinical development efforts reflects our confidence in the potential therapeutic benefit of our unique gut-selective JAK inhibitor,” Brett Haumann, M.D., chief medical officer at Theravance Biopharma, said in a news release.
“We have established an excellent working relationship with our partner Janssen, and we are advancing TD-1473 in inflammatory intestinal diseases with the precise goal of expanding the therapeutic index beyond that of conventional systemic therapies, which are known to carry dose-limiting safety profiles.”
For more information about this trial, go to its official website.