Celiac.com 06/02/2014 - Despite following a gluten-free diet, many people with celiac disease continue to have symptoms, and to suffer from ongoing small intestinal inflammation. Can a drug be created to alleviate such symptoms and inflammation, and protect celiacs on a gluten-free diet against small amounts of gluten contamination?
San Carlos California-based Alvine Pharmaceuticals is conducting a phase 2 trial to determine whether their drug, ALV003, an orally administered mixture of 2 recombinant gluten-specific proteases can protect celiac disease patients from gluten-induced mucosal damage. For this trial, Alvine is working with researchers Marja-Leena Lähdeaho, Katri Kaukinen, Kaija Laurila, Pekka Vuotikka, Olli-Pekka Koivurova, Tiina Kärjä-Lahdensuu, Annette Marcantonio, Daniel C. Adelman, and Markku Mäki.
For their Phase 2 trial, the research team first established two grams of gluten per day as the optimal challenge dose for their 6-week gluten study. They then randomly assigned 20 adults with biopsy-proven celiac disease to receive ALV003, and twenty-one to receive a placebo. Both groups also received 2 grams of gluten each day. The team conducted duodenal biopsies at baseline, and after gluten challenge, focusing on the ratio of villus height to crypt depth and densities of intraepithelial lymphocytes.
A total of seven patients dropped out due to adverse reactions. Four were receiving ALV003, and three were receiving the placebo. Sixteen patients given ALV003 and 18 given placebo were eligible for efficacy evaluation. Biopsies from subjects in the placebo group showed evidence of mucosal injury after gluten challenge, with average villus height to crypt depth ratio changed from 2.8 before challenge to 2.0 afterward. (P = .0007; density of CD3þ intraepithelial lymphocytes changed from 61 to 91 cells/mm after challenge; P = .0003).
However, the team saw no significant mucosal deterioration in biopsies from the ALV003 group. The two groups showed no significant differences in symptoms, though they did show substantial differences in morphologic changes, and CD3þ intraepithelial lymphocyte counts differed significantly from baseline to week 6 (P = .0133 and P = .0123, respectively). This small, but important, step means that ALV003 did provide significant protection against gluten-induced gut damage for people with celiac disease on an otherwise gluten-free diet, which means that Alvine can continue to the next phases in the development process.
If successful, glutenase ALV003 will be the first drug to protect people with celiac disease against gut damage from small amounts of gluten.
- Clinicaltrial.gov, Numbers: NCT00959114 and NCT0125569