Experimental drug may protect celiac-disease patients from inadvertent gluten exposure

Last Updated: 2018-05-29

By Megan Brooks

NEW YORK (Reuters Health) - An experimental monoclonal antibody (AMG 714) may help protect patients with celiac disease from developing symptoms such as gut pain and diarrhea after inadvertent exposure to gluten, according to a proof-of-concept study.

But the drug did not show a significant effect on villous-height-to-crypt-depth ratio, the primary endpoint, researchers report.

The study, a phase 2a, placebo-controlled trial, was presented during a press briefing May 21 ahead of a presentation June 4 at Digestive Disease Week (DDW) 2018 in Washington, D.C.

"It is virtually impossible for celiac-disease patients to completely avoid gluten permanently and this leads to many patients on a gluten-free diet being inadvertently exposed to gluten," study chief Dr. Francisco Leon from Celimmune in Bethesda, Maryland, told the briefing. About 30% to 50% of all patients on a gluten-free diet continue to have signs and symptoms of gluten exposure, leading to reduced quality of life, he noted.

AMG 714 blocks interleukin-15, an important mediator of celiac disease, and "offers hope of relief for celiac disease patients who are inadvertently exposed to gluten," said Dr. Leon.

The study lasted 12 weeks and included 60 patients with celiac disease who were randomly allocated to AMG 714 (150 mg or 300 mg) or matching placebo given by subcutaneous injection six times over 10 weeks.

A subset of 49 patients received a high-dose gluten challenge of about 2.5 g/day for 10 weeks. Another 11 patients, who showed mucosal atrophy at baseline and were found to be exposed to hidden gluten contamination while on a gluten-free diet, did not receive the additional gluten challenge.

"While the primary endpoint in the study, the effect on Villous Height to Crypt Depth ratio (VH:CD) was not statistically significant, AMG 714 ameliorated gluten-triggered effects across a range of endpoints," Dr. Leon and colleagues report in their meeting abstract.

For patients taking 300-mg AMG 714, "meaningful differences" (P=0.02) were observed in the Celiac Disease Patient-Reported Outcome, they note. Protection against gluten-triggered symptoms was seen in the Bristol Stool Form Scale (BSFS) scores as well, with patients in the placebo group experiencing an increase in diarrhea, which was not seen in the patients taking 150 mg (P=0.01) and 300 mg (P<0.01) of AMG 714, the researchers report.

At week 12, despite high-dose gluten challenge, none of the patients who took the 300-mg dose was judged by the lead investigator to have active disease compared with 33% of the patients in the placebo group. No symptoms associated with accidental gluten consumption were seen in the subgroup that did not receive the gluten challenge.

There were no serious adverse events or safety signals in the study. The most common adverse events related to AMG 714 included injection site reactions and pain, headache and upper respiratory tract infection.

"It's important to note that AMG 714 is intended to protect against modest contamination of gluten and not against the effects of deliberately eating large amounts of gluten, like bread or pasta," Dr. Leon told the briefing. "But we know that people with celiac disease are inadvertently exposed to gluten and it is our hope that AMG 714 will allow these patients to experience fewer gluten-triggered events."

The study was funded by Celimmune, which was acquired by Amgen in 2017 after study completion. Dr. Leon is a consultant for Amgen.

SOURCE: https://bit.ly/2sbu9Ra

Digestive Disease Week (DDW) 2018.