Update on IIB Trial of Larazotide Acetate

It seems that medical science is one step closer to having a drug that can be used to help treat celiac disease. Alba Therapeutics recently announced the successful results of its Phase IIb trial of larazotide. While all the data has not been released or published in a journal article, it is clear that the study met its objectives. This means that larazotide acetate was shown to be both safe and effective in the specific setting of the research. It also means that Alba Therapeutics can now move on to the next stage of testing, Phase III, so that it is closer to becoming an available medication that doctors can prescribe.

Even though the FDA has put larazotide acetate on the “Fast Track” of development, this is not actually what most people would consider fast. Also, this drug is not meant to treat celiac disease without the gluten-free diet. It is meant to be used with the diet. Since so many people actually still eat gluten, either accidentally, or on purpose for a special occasion, or if no alternative food was available, larazotide may prevent them from having symptoms Larazotide acetate is the first “tight junction regulator.” People with celiac disease have a “leaky gut,” which means that parts of the gluten molecule get past the intestinal barrier that is supposed to keep them out. The entry of these pieces of gluten is the beginning of a cascade of reactions which cause the damage to the intestine and the symptoms of celiac disease.

It has been estimated that some 70% of people with celiac disease still get the occasional exposure to gluten. If the intestinal lining can be made less leaky, this occasional exposure might not cause damage or symptoms. That would improve how many patients feel. It would also make them less worried about eating at a restaurant or at a friend’s house.

While larazotide will not replace the gluten-free diet, most people with CD would still be very happy to finally have something to help them manage their illness. The official description of this study, as listed on the U.S. National Institutes of Health clinical
trial website is as follows: “A randomized, double-blind, placebo-controlled Phase 2B study to evaluate the efficacy and safety of Larazotide Acetate in the treatment of patients with celiac disease who have persistent symptoms despite being on a gluten-free diet.”

The study began in 2011, and according to the press release from Alba Therapeutics, the trial is finished, although researchers are still reviewing data and getting ready to publish it. The study was a double-blind, placebo-controlled trial of larazotide acetate. There were four groups. Three of the groups received larazotide three times a day, either 0.5 mg, 1mg, or 2 mg. The fourth group got a placebo. The length of treatment was 12 weeks.

All patients in the study had to have both positive antibody studies and biopsy-proven celiac disease. They had to have been on a gluten-free diet for at least 12 months but still have symptoms. They had to have symptoms that could be followed with the standard CeDGSRS score, a questionnaire that indicates symptom severity. They could not have any other gastrointestinal disorder or have been diagnosed with refractory celiac disease. There were other inclusion and exclusion criteria, but these were the most important in selecting a group of people who were somehow getting gluten despite believing themselves to be on a gluten-free diet. Larazotide would be expected to help them.

There were patients recruited from all over the country, with a total of 342 people completing the study. The “primary endpoint,” which is the result being evaluated, was an improvement in symptoms, as measured by the standard CeD-GSRS score. This endpoint was met, meaning that there was a statistically significant improvement of symptoms in the patients getting larazotide.

The best dose to use and the amount of improvement seen will not be available until all of the results published, which will occur in the “near future.”

Alba Therapeutics said that the results were good enough for them to plan the next stage, Phase III. Phase III studies are designed to be definitive and results lead to a decision whether or not the drug will make it to market.

This may very well be the first drug treatment for celiac disease.

For more information, check out: Larazatide Acetate (AT-1001) for Celiac Disease: Recently Published Results & Larazotide Acetate (AT-100) For Celiac Disease: Research Continues

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References
Alba Therapeutics. Alba Therapeutics Announces Positive Results of Phase IIb Trial in Celiac Disease. Press Release February 11, 2014. http://www.albatherapeutics.com/tabid/108/Default.aspx
Accessed February 11, 2014.
U.S. National Institutes of Health. ClinicalTrials.gov. A Double-blind Placebo-controlled Study to Evaluate Larazotide Acetate for the Treatment of Celiac Disease. http://clinicaltrials.gov/ct2/show/study/NCT01396213?term=larazotide+acetate+and+celiac+disease&rank=1#locn
Accessed February 11, 2014.
Paterson BM , Lammers KM , Arrieta MC et al. The safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT-1001 in coeliac disease subjects: a proof of concept study . Aliment Pharmacol Ther 2007; 26:757-66.
Leffler D.A., Kelly C. P., Abdallah H. Z., et al. A Randomized, Double-Blind Study of Larazotide Acetate to Prevent the Activation of Celiac Disease During Gluten Challenge. Am J Gastroenterol advance online publication, 24 July 2012.