The multicenter, randomized, double-blind, placebo-controlled, parallel, adaptive two-stage trial (NCT02895100) will assess the effectiveness, safety and tolerability of PTG-100 in about 240 adults with moderate to severe UC.
Researchers will randomly assign patients to one of three doses of PTG-100 — 150, 300, or 900 mg — or to a placebo. Patients will receive doses once a day orally for 12 weeks, followed by four weeks of safety assessment.
PTG-100 is an alpha-4-beta-7 (α4β7) integrin-specific antagonist peptide. α4β7 integrin binds with MAdCAM-1, a protein that resides mostly in the gastrointestinal vasculature, or circulatory system.
Protagonist will conduct an interim futility analysis by mid-2017 to test PTG-100’s performance against the placebo. If PTG-100 has failed to outperform the placebo by then, investigators will assign one or two optimal doses of the therapy to patients chosen randomly.
The primary measure of PTG-100’s effectiveness will be how many patients’ disease goes into clinical remission, compared with the placebo users, after 12 weeks. Clinical remission is defined as normal stool frequency without bleeding, and improvement in endoscopic scores, as measured by the Mayo Scoring System. An endoscope is an instrument used to examine body cavities.
Safety will be assessed by comparing the number of adverse events among patients taking PTG-100 with the number of events among the placebo group for up to 16 weeks.
Researchers will also make other treatment and safety assessments, evaluate PTG-100 properties, and look at additional biomarkers of disease activity.
The trial will be conducted at 100 sites in the United States, Canada, Europe, Asia, Australia, and New Zealand. Additional information about it can be found here.
“We are very pleased to advance our oral, alpha4beta7 integrin-specific antagonist peptide candidate, PTG-100, into this clinical proof-of-concept and dose optimization study,” Richard Shames, MD, chief medical officer at Protagonist said in a press release. “We expect to complete the study and report top-line data in the second half of 2018.”
“PTG-100 is the most advanced asset to have emerged from our proprietary oral peptide technology platform that enables de novo discovery and optimization of novel peptides for protein:protein interaction (PPI) targets,” said Dinesh Patel, PhD, Protagonist’s president and chief executive officer.
“Since these PPI targets have typically been approached by injectable antibody drugs, our platform offers the distinct advantage of generating oral therapeutic assets against the same PPI targets utilized by approved antibody drugs,” he added. “We look forward to advancing PTG-100 to clinical proof-of-concept in patients with ulcerative colitis and applying our technology platform to discovering other novel peptidic assets to address unmet medical needs.”