Phase 2b Trial of Ulcerative Colitis Treatment Discontinued

This morning, it was announced that the Phase 2b PROPEL study of PTG-100 in patients with ulcerative colitis (UC) has been discontinued.

Developer of the drug, Protagonist Therapeutics, made its decision after an analysis by the Data Monitoring Committee (DMC) showed that the treatment was unlikely to demonstrate a clinical benefit in the patient population. Data from only 65 of the enrolled 240 patients was reviewed before the committee ruled that it would be futile to continue.

PTG-100 was being evaluated for safety, efficacy, and dose-optimization in the global, randomized, double-blind, placebo-controlled, 2-stage adaptive clinical trial.

"We are very disappointed with this futility-based outcome which was also accompanied by an unexpectedly high placebo rate. We will conduct an extensive review of the complete dataset on the totality of patients enrolled in the trial before making any further decisions about the future development of PTG-100," said Dinesh V. Patel, Ph.D., President and Chief Executive Officer of Protagonist Therapeutics in a press release.

UC is characterized by inflammation and ulcers in the colon and rectum, and it can lead to symptoms like abdominal pain, diarrhea and bloody stools. The primary efficacy endpoint of the study was the proportion of patients who achieve clinical remission as defined by rectal bleeding, stool frequency, and endoscopic subscores of the Mayo score.

For 12 weeks, 3 doses (150 mg, 300 mg, and 900 mg) of PTG-100 were compared to placebos in patients with moderate to severe UC.

Further review of unblinded efficacy and safety data from the trial is being conducted; however, Protagonist is notifying investigators that randomization of potential participants and further treatment of patients currently in the study is to be discontinued.

"We are very grateful to the patients and investigators who participated in the PROPEL trial,” said Patel. “Protagonist remains committed to progressing its other peptide-based assets currently in clinical development, PTG-200 and PTG-300, and to discovering new peptide-based therapeutic entities to address significant unmet medical needs."

The current standard of care for more than 80% of all people with mild-to-moderate UC is anti-inflammatory medication. In PTG-100, an investigational oral GI-restricted alpha-4-beta-7 integrin antagonist peptide, the alpha-4-beta-7 binds to the MAdCAM-1 protein that resides in the gastrointestinal (GI) vasculature that acts as a homing receptor for lymphocytes. A blockage of the receptors lowers the levels of lymphocytes, thus lessening inflammation.

In addition to its work in UC, Protagonist has also been testing PTG-100 in chronic pouchitis. The company has made clear its intentions to postpone a decision regarding the initiation of a Phase 2/3 clinical trial of PTG-100 in that indication until a full review of the interim data from the PROPEL study in UC has been completed.

In December, Rare Disease Report spoke with Paul P. Doghramji, M.D., of Brookside Family Practice & Pediatrics in Pennsylvania about the challenges of treating pediatric UC.

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