Clinical Trial of Potential Ulcerative Colitis Treatment Enters Next Phase

Clinical Trial of Potential Ulcerative Colitis Treatment Enters Next Phase

Theravance Biopharma announced the first dosing of a patient with moderate to severe ulcerative colitis  enrolled in its Phase 1b clinical trial, which is evaluating the investigational drug TD-1473, a pan-Janus kinase (JAK) inhibitor with the potential to treat a range of inflammatory intestinal diseases.  The clinical trial is recruiting patients.

Proinflammatory cytokines play an important role in inflammatory intestinal diseases, many of which signal via the JAK/signal transducer and activator of transcription (STAT) pathway. TD-1473, a novel pan-JAK inhibitor, was designed to inhibit JAK in the gastrointestinal tract upon oral dosing without significant systemic exposure.

The 28-day, multi-center, randomized, double-blind, placebo-controlled study (NCT02818686) is examining the safety, tolerability, pharmacokinetics, and pharmacodynamics of TD-1473 in patients with moderate-to-severely active ulcerative colitis UC.

Forty enrolled patients with UC will be assigned randomly to receive either one of three doses of TD-1473 or a placebo for 28 days. The trial’s primary goal is the assessment of safety and tolerability through examination of adverse events, and the evaluation of TD-1473’s plasma exposure following administration.

The trial also will explore the biologic effect associated with TD-1473 through biomarker analysis and clinical, endoscopic and histologic assessments (secondary endpoints). These include the assessment of the drug’s effect on C-reactive protein, fecal calprotectin, changes in partial Mayo score, and endoscopic and histologic assessments to determine improvements in disease activity. Results are expected by mid-2017.

Theravance recently reported positive data from a Phase 1 study (NCT02657122) in healthy volunteers demonstrating that treatment with TD-1473 is safe and well-tolerated as a single dose (up to 1000 mg), and as a daily dose (up to 300 mg) given for 14 days, without causing serious adverse events.

Trial participants also presented high stool concentrations of TD-1473, comparable to concentrations related with efficacy in preclinical models of ulcerative colitis. Preclinical trial results also demonstrated penetration of TD-1473 into the intestinal membrane, as well as into the intestinal wall.

Generally, results from the TD-1473 clinical development program support Theravance Biopharma’s view that a therapeutically relevant level of TD-1473 can be delivered to and penetrate the colon wall, with minimal release into systemic circulation.

“The start of our Phase 1b clinical trial is the latest development milestone for our TD-1473 program, which we believe represents a potentially transformative approach to treating inflammatory intestinal diseases. The totality of the data generated … to date provides support for our strategy of targeting JAK inhibition to affected tissues within the intestinal tract in order to achieve desired therapeutic results with a favorable safety and tolerability profile,” Brett Haumann, MD, chief medical officer at Theravance Biopharma said in a press release.