Investigation of new drug that could help patients struggling with symptoms gets NIH grant
By Amy Ratner
Beyond Celiac Medical and Science News Analyst
Researchers developing a drug to treat celiac disease will launch a new clinical trial early next year as they further investigate whether it can effectively break down gluten in the stomach and render the harmful protein inactive.
ImmunogenX, a California company focused on the treatment of celiac disease, recently received a grant from the National Institutes of Health to study latiglutenase. Latiglutenase is made of a combination of two enzymes that degrade gluten and could relieve symptoms and prevent intestinal damage in those who have celiac disease.
The study will also test CypCel, a diagnostic tool the company is developing to monitor intestinal damage in celiac disease patients. Joseph Murray, M.D., a celiac disease expert who is a professor of medicine at the Mayo Clinic and a member of the Beyond Celiac Scientific/Medical Advisory Council, and Jack Syage, Ph.D., ImmunogenX chief executive officer, will be the lead investigators.
The two-year study conducted at the Mayo Clinic will monitor how well latiglutenase degrades gluten in a controlled clinical setting. Study participants will be given a specific amount of gluten over a specific time. Some will get latiglutenase, while others will receive a placebo.
All will have intestinal biopsies done before and after the study to determine whether there is any change in their intestinal lining. Researchers will measure villous height-to-depth ratio, a standard way of evaluating how much damage gluten has caused for patients who have celiac disease. Villi, which are finger-like projections in the intestinal lining responsible for the absorption of nutrients, are separated by crevices. In patients with active celiac disease, the villi get flattened and the crevices deepen.
Additionally, scientists will use CypCel, a diagnostic test based on a drug biomarker to measure how healthy the small intestine is before and after the gluten challenge. In the test, a single dose of the widely-used cholesterol-lowering agent, simvastin, is given to a patient. Its concentration is then measured to determine how healthy the intestinal lining is, with a reduced concentration correlating with intestinal recovery.
Study participants will also provide details about symptoms through the Celiac Disease Symptom Diary©, a patient-reported outcome tool often used in celiac disease clinical trials.
Patient-reported outcome – a report on the status of a patient’s health condition that comes directly from the patient, without interpretation by another party
Latiglutenase, also called IMGX-003, would be used along with a gluten-free diet to protect patients from inadvertent consumption of gluten. Patients often report how difficult it is to follow the diet and are often exposed to gluten despite their best efforts, especially when they eat away from home. Estimates vary, but studies have consistently shown that celiac disease patients continue to have intermittent or ongoing disease activity even when on the gluten-free diet.
Results from the most recent latiglutenase trial, called the CeliAction study, were disappointing because it did not meet its primary endpoint of showing that latiglutenase resulted in statistically significant intestinal healing compared to a placebo. Study participants showed improvement through an intestinal biopsy, blood test results and lessening of symptoms whether they were given the drug or not.
Researchers theorize that this was a result of a trial effect, in which patients change their behavior – in this case following the gluten-free diet more strictly than they normally would – because they are being observed.
Researchers did find that study participants with positive celiac disease blood tests who got the highest doses of latiglutenase showed significant improvement in symptoms, including abdominal pain, bloating, tiredness and constipation. These results suggest that latiglutenase could be most helpful to patients most in need of a drug to treat celiac disease in addition to the diet.
However, the new NIH trial will not focus on that subset of symptomatic patients. Syage said the study will be based on patients who have their celiac disease relatively well controlled. The amount of the NIH grant that will be used for the study was not made public. It was awarded by the National Center for Complementary and Integrative Health, which was seeking natural product candidates tested for a biological signature and a clinical outcome that correlate. Latiglutenase fit the description because the study would use biopsy results and patient reported symptoms.