Celiac.com 12/13/2011 - Alvine Pharmaceuticals, Inc. has announced that efficacy data from its Phase 2a clinical trial of ALV003 shows that oral ALV003, administered as part of a gluten free diet, reduced gluten-induced intestinal mucosal damage in people with well-controlled celiac disease.

Alvine presented the study findings in a session of the 19th United European Gastroenterology Week (UEGW) in Stockholm.

Photo: CC - Montage Communications"These results are groundbreaking as they demonstrate for the first time, in a controlled clinical trial, that a drug has the potential to diminish gluten-induced injury in celiac disease patients," says Markku Maeki, M.D., chair and professor of pediatrics at the University of Tampere and Tampere University Hospital in Finland, and coordinating investigator of the ALV003 Phase 2a trial.

Most people with celiac disease control their disease by following the gluten-free diet that is the only current treatment.

Of those, many still suffer gluten-related discomfort and gut damage. In fact, Mr. Maeki adds, "up to 60 percent of adult celiac disease patients continue to experience symptoms and up to 80 percent continue to have persistent intestinal inflammation despite adhering to a strict gluten-free diet."

Since gluten is so common in food processing, it's almost impossible to avoid ingesting tiny amounts of gluten, even for people with celiac disease.

Gluten contamination commonly occurs via cross-contamination in the processing of food products, incorrect or inaccurate labeling, lack of dietary education and awareness, and even due to willful back-sliding on the part of otherwise faithful gluten-free dieters.

According to Dr. Maeki, non-dietary treatment options that either eliminate, or significantly reduce gluten ingestion by those attempting a gluten-free diet are needed, "[b]ecause it is all but impossible to avoid gluten, even while adhering to a gluten-free diet, celiac patients are at continued risk for gastrointestinal symptoms and potentially serious long-term medical consequences."

The study is constructed as a double-blind, placebo-controlled Phase 2a clinical trial on 41 adults with well-documented celiac disease, who had followed on a gluten-free diet for one or more years. Study participants were randomly given ALV003 or a placebo each day for six weeks. At the same time, they were given 2g of gluten in the form of bread crumbs.

Each member of the study received small bowel biopsy at the beginning of the trial, and then again after six weeks of daily gluten challenge.

The study's primary endpoint was intestinal mucosal morphometry (villus height:Crypt depth)(or vh:Cd) measured at baseline and at six weeks.

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

The study was statistically powered for the primary endpoint of change in Vh:Cd with six weeks of gluten exposure. Results from 34 celiac disease patients eligible for analysis showed that after six weeks:

--  Biopsy data demonstrated significantly less 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+ alpha/beta and gamma/delta subsets, which measure inflammatory response, were essentially unchanged in the ALV003-treated patients but significantly increased in the placebo-treated patients.

    ------------------------------------------------------------------------
                                    Change from Week 0                     p value
                                         to Week 6
    ------------------------------------------------------------------------
                           ALV003 (n=16)      Placebo (n=18)
    ------------------------------------------------------------------------
     Vh:Cd                                -0.2                -0.8         0.0133
    ------------------------------------------------------------------------
      CD3+ IELs                      +2.4               +30.8        0.0152
    ------------------------------------------------------------------------
    CD3 alpha/beta IELs         -1.8               +24.2         0.003
    ------------------------------------------------------------------------
    CD3 gamma/delta IELs    +0.5               +10.9         0.003
    ------------------------------------------------------------------------
            
--  Overall GSRS scores and scores for indigestion and abdominal pain symptoms were lower in ALV003-treated patients than in placebo-treated patients, although the results were not statistically significant.

--  No statistically significant changes were observed in celiac disease serology tests between the ALV003 and placebo-treated patients, although positive trends were observed for tissue transglutaminase (tTG) and deamidated gliadin peptide (DGP) antibodies 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 distention, flatulence, eructation, abdominal pain and diarrhea.


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