Latiglutenase did not improve histologic and symptomatic measures of disease activity in patients with symptomatic celiac disease compared with placebo in a phase 2 study.
However, “all study groups including placebo had a substantial significant improvement in both histologic scores and symptoms,” which investigators suggested may be due to “a strong trial effect.”
Joseph A. Murray
Latiglutenase (IMGX-003, Immunogenics; formerly ALV003, Alvine) is an oral mixture of two recombinant gluten-targeting proteases in development as a nondietary therapy for celiac disease. It is designed to degrade gluten into non-immunotoxic fragments when taken with meals. A previous randomized controlled trial showed latiglutenase attenuated mucosal injury in patients who adhered to a gluten challenge for 6 weeks.
To evaluate the ability of latiglutenase to reduce mucosal injury in celiac patients who were symptomatic despite adhering to a gluten-free diet, Joseph A. Murray, MD, of the Mayo Clinic in Rochester, Minn., and colleagues performed a phase 2 double blind, dose-ranging study of 494 patients with moderate-to-severe symptoms in North America and Europe from August 2013 to December 2014. All patients reported adhering to a gluten-free diet for at least 1 year, which they continued to do through the trial, and all had histologic evidence of significant duodenal mucosal injury at baseline.
Murray and colleagues randomly assigned them to receive placebo or latiglutenase at 100, 300, 450, 600 or 900 mg per day for 12 or 24 weeks. Change in villous height:crypt depth ratio based on biopsies taken at weeks 12 and 24 served as the primary endpoint.
In the modified intent-to-treat population, latiglutenase and placebo groups showed comparable changes in villous height:crypt depth ratio.
“There was a statistically significant, but clinically trivial, greater effect of placebo on [villous height:crypt depth ratio] than on the treatment groups,” the researchers wrote.
Further, numbers of intraepithelial lymphocytes, serology test results, frequency of symptoms, and safety outcomes were also comparable between groups.
Because the study instructions “may have unintentionally affected patient behavior and improved the level of adherence to the [gluten-free diet],” along with a number of other possible sources of variability that may have affected the study outcome, Murray and colleagues concluded that “a key variable that will need to be addressed in clinical trials in celiac disease, in which healing of injured mucosa is the overall objective, is the need to design a study that overcomes or at least minimizes the trial effect.” – by Adam Leitenberger
Disclosures: Murray reports he has received grant support from the National Institutes of Health, Alba Therapeutics, the Oberkotter Foundation, and the Broad Medical Research Program at Crohn’s & Colitis Foundation of America; has served on the advisory boards of Celimmune, AMAG Pharmaceuticals, Entera Health Inc, Sonomaceuticals, BioLineRx, GlaxoSmithKline, Genentech, and Glenmark Pharmaceuticals; has served as a consultant to
Boehringer Ingelheim; is a patent holder with Miomics, and holds equity options in Torax. Please see the full study for a list of all other researchers’ relevant financial disclosures.