By Amy Ratner, Medical and Science News Analyst
Most patients in the CeliAction clinical trial who received a drug to treat celiac disease did no better than those who were given a placebo, study results published in the journal Gastroenterology show.
Study participants received varying doses of latiglutenase, a combination of two enzymes that break down gluten, or a placebo, which does not include the actual drug. All showed improvement through an intestinal biopsy, blood test results and lessening of symptoms. But overall those who were given the drug did not do better compared to those who were not given the drug.
Lead author Joseph Murray, M.D. of the Mayo Clinic in Rochester, Minnesota, attributed the across-the-board improvement to a “strong trial effect.” He noted that because participants had to take the drug or placebo three times a day, they had a continual reminder of the gluten-free diet and might have changed their behavior to follow it more strictly.
That, ultimately, caused the Phase 2 trial to fail to meet its primary goal of showing that latiglutenase can reduce damage to the intestine compared to the placebo.
Definition: Trial effect describes the benefit study participants experience simply by virtue of their being involved in the trial, including the change of a patient's own behavior as a result of being under observation.
However, researchers at ImmunogenX, the clinical stage biopharmaceutical company developing latiglutenase, are continuing to look at data from the trial related to specific groups of patients. They are optimistic about the future of the drug and its ability to help these patients improve their quality of life and better manage celiac disease, according to the company. And plans are in place for the next Phase 2 clinical trial.
Original theory not supported
The recent CeliAction trial included nearly 500 celiac disease patients who had been on the gluten-free diet for a least one year and who had moderate to severe symptoms and intestinal damage. It was conducted from August 2013 to December 2014 throughout Europe and North America and had been widely publicized among celiac disease patients.
“This study of potential therapeutic intervention in patients with symptomatic celiac disease and evidence of mucosal injury is remarkable in its design, rigor, size and outcome,” the authors wrote. But they had to conclude, “The result of the study did not support the original hypothesis.”
Latiglutenase was originally developed by Alvine Pharmaceuticals, and ImmunogenX, which is focused on the treatment of autoimmune and gastrointestinal diseases, acquired the non-cash assets in February 2016. Earlier Phase 1 and 2 clinical trials done by Alvine had produced promising results.
Additional review of study findings
In their ongoing review of the CeliAction results, ImmunogenX and study investigators found that participants with positive celiac disease blood tests who got the highest doses of latiglutenase showed significant improvement in abdominal pain and bloating, although this was not the case for patients who had negative blood tests.
Among the 398 patients with a positive blood test, severity of abdominal pain improved for 57 percent and bloating for 44 percent. Tiredness and constipation were also shown to have decreased in these patients.
Celiac disease patients who are monitored after diagnosis present a complicated picture of symptoms, blood test results and signs of intestinal damage revealed through a biopsy. Some show evidence of the disease by all three measures, others only two and some only when a biopsy is done.
Given this complexity, information collected from the large number of patients in the CeliAction study offers researchers a continuing chance to gain new insights.
“While the published study showed no overall benefit, we have since discovered that people with symptoms and elevated celiac disease antibodies did have a significant benefit,” said Peter Green, M.D., a study author and director of the Celiac Disease Center at Columbia University. “We are thrilled with that because it gives the medicine an ongoing opportunity to get out there to help patients.”
Jack Syage, Ph.D., ImmunogenX chief executive officer, said the subset of patients who showed improvement are the ones most in need of a therapy. “The symptom improvements are greater for more symptomatic patients which means the analysis says we are heading in the right direction,” he said.
A separate study by Dr. Green and colleagues published this year in the journal Alimentary Pharmacology and Therapeutics showed that 23 percent of patients with moderate to severe symptoms had positive results on at least one of three different types of celiac disease blood tests. That study also concluded that celiac disease antibodies were associated with intestinal damage.
Digestive Disease Week 2017
ImmunogenX was recently selected through a peer-reviewed process to give a lecture presentation covering the symptom improvement results from the CeliAction study at the upcoming Digestive Disease Week (DDW). The company has also submitted these results for publication in a peer-reviewed medical journal.
DDW is the world's largest gathering of physicians, researchers and industry in the fields of gastroenterology, hepatology, and endoscopy, and late breaking developments in celiac disease are often presented at the annual meeting.
Two research abstracts from Beyond Celiac have also been accepted for poster presentations. Staff and some members of the research teams will attend DDW and follow celiac disease news at the conference.
You can read more about the CeliAction study here and ImmunogenX here.
Beyond Celiac will continue to explore the issues raised by the CeliAction study. To keep up-to-date on this and other research news, sign up for our Research Opt-In here.