Alvine Pharmaceuticals, Inc. has announced the presentation of data from a Phase 2A trial of its lead compound, ALV003, at the 2012 Digestive Diseases Week (DDW) meeting held in San Diego, California. The study results met the primary endpoint of demonstrating that oral ALV003, administered in the context of a gluten free diet (GFD), can diminish gluten-induced intestinal mucosal injury in well-controlled celiac disease patients. The company plans to initiate a Phase 2B trial later this year.
The clinical study presented was a double-blind, placebo-controlled Phase 2A trial evaluating the efficacy and safety of ALV003 administered orally for six weeks. In the study, well-controlled, well-characterized adult celiac disease patients who had been maintained on a GFD for at least one year, were randomized to receive ALV003 or placebo daily for six weeks; patients were instructed to ingest 2g of gluten in the form of bread crumbs at the same meal as the study treatment. Study participants underwent small bowel biopsy prior to randomization and again, at the end of the six week challenge. The study met its primary endpoint, which was a clinically and statistically meaningful difference in intestinal mucosal morphometry (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. The main study results were as follows:
- Biopsy data demonstrated significantly reduced small intestinal mucosal injury as measured by Vh:Cd in patients treated with ALV003 than in placebo-treated patients (p=0.0133).
- IELs, including CD3+ and CD3+ aB and subsets, which measure inflammatory cellular responses were significantly increased in the placebo-treated patients, but were essentially unchanged in the ALV003-treated patients.
- Overall GSRS scores and scores for indigestion and abdominal pain symptoms favored the ALV003-treated patients over the placebo-treated patients, although the results were not statistically significant.
- No statistically significant changes were observed (as expected, given the short duration of the study) in celiac-disease serology tests between the ALV003 and placebo-treated patients, although positive trends were observed for tissue transglutaminase and deamidated gliadin peptide antibody titers in the ALV003-treated group, a measure of immune responsiveness.
- No serious adverse events were reported; non-serious adverse events consistently occurred more frequently in the placebo-treated patients. Adverse events that occurred in 10 percent or more patients included abdominal distension, flatulence, eructation, diarrhea, nausea, headache and fatigue.
“This is the first time that we are aware of, that any potential therapeutic intervention in phase 2 development for celiac disease has met its prespecified primary endpoint with both clinical and statistical significance,” said Daniel Adelman, M.D., Alvine’s Senior Vice President and Chief Medical Officer. “We are very encouraged by these results and are currently enrolling celiac disease patients in a study to evaluate and measure celiac-specific symptoms as a function of gluten exposure. In addition, we are planning to initiate a phase 2B clinical trial later this year.”
Information on Alvine’s current clinical trial titled “Evaluation of Patient Reported Outcome Instruments in Celiac Disease Patients” can be found at the NIH website: http://clinicaltrials.gov/ct2/show/NCT01560169