Celiac.com 07/23/2012 - At 2012 Digestive Diseases Week in San Diego, California, Alvine Pharmaceuticals, Inc. announced the publication of data from Phase 2A trial of its main celiac disease compound, ALV003.

The results show that ALV003, orally administered to celiac disease patients on a gluten free diet, significantly reduces gluten-triggered intestinal mucosal damage.

For the trial, 41 adults with clinically proven celiac disease who had followed a gluten-free diet for at least one year were randomly given ALV003 or a placebo each day for six weeks. During that time, they also received 2g of gluten in the form of bread crumbs.

Participants received a small bowel biopsy prior to randomization and again, at the end of the six week challenge.

The results showed that the study met its primary endpoint of a clinically and statistically meaningful reduction in intestinal mucosal damage in celiac patients on a gluten-free diet. Damage was measured by the ratio of the villus height to crypt depth, or Vh:Cd between the ALV003 and placebo treated groups over the six week study period.

Secondary endpoints included change in intraepithelial lymphocyte (IEL) density, gastrointestinal symptoms as measured by Gastrointestinal Symptom Rating Scale (GSRS) scores, celiac serologies, safety and tolerability.

Each subject received small bowel biopsy at the start of the trial, and again after six weeks of daily gluten challenge.

When researchers compared biopsy results from 34 patients, they found significantly less small intestinal mucosal damage in patients treated with ALV003 than in placebo-treated patients (p=0.013).

Placebo-treated patients suffered worse damage and symptoms. Most often, these included abdominal distention, flatulence, eructation, abdominal pain and diarrhea.

The published data shows that:

• Biopsy results for patients who received ALV003 had significantly reduced small intestinal mucosal damage compared with placebo-treated patients (p=0.0133).
• For placebo-treated patients, IELs, including CD3+ and CD3+ aB and subsets, which measure cellular inflammation responses, were significantly higher, but were mostly normal in the ALV003-treated patients.
• ALV003-treated patients had better overall GSRS scores and scores for indigestion and abdominal pain symptoms, compared with placebo-treated patients, though the results were not statistically significant.
• Patients reported no serious adverse events, however, placebo-treated patients reported more regular and consistent non-serious adverse. Such events that occurred in 10 percent or more patients included abdominal distention, flatulence, eructation, diarrhea, nausea, headache and fatigue.
• Celiac-disease blood tests revealed no significant changes between the ALV003 and placebo-treated patients, though results did show positive trends for tissue transglutaminase and deamidated gliadin peptide antibody titers in the ALV003-treated group, which indicates improved immune response.

Daniel Adelman, M.D., Alvine's Senior Vice President and Chief Medical Officer, says that the trial results represent the first time that any such treatment for celiac disease has met its pre-specified primary endpoint of providing protection against damage from gluten-exposure in celiac disease patients, with data that is both clinically and statistically significant.

Such a drug could help to protect gluten-free celiac disease patients against accidental gluten contamination.

The company plans to initiate a Phase 2B trial later this year.

• Read the abstract of the presentation (Sa1342) on the DDW website.
• Review information on Alvine's current clinical trial titled "Evaluation of Patient Reported Outcome Instruments in Celiac Disease Patients" at the NIH website.