Crohn's disease is a type of inflammatory bowel disease (IBD) that usually affects the intestines, but may occur anywhere in the nine-meter-long alimentary canal that starts at the mouth and finishes at the end of the rectum (anus).
The exact cause of Crohn's disease is unknown, but we know it is an autoimmune disorder, where the body's immune system mistakenly attacks and destroys healthy tissue. There are different forms of Crohn's disease, depending on what part of the body is affected.
The trial, called TRUST-I (TRichUris Suis ova Trial), is a Phase 2 clinical trial of the biologic treatment TSO (Trichuris suis ova, also known as CNDO-201) in patients with Crohn's disease.
New Biologics Act As Immune RegulatorsTSO is a new drug, taken by mouth, that contains microscopic eggs of the pig whipworm parasite. It acts as a natural regulator of the immune system, by controlling T-cells, a group of white blood cells, and cytokines, signalling proteins that deal with inflammation, among other things.
In a pig, the eggs grow into whipworms and reproduce, without causing harm to the animal. In a human, the same eggs live no more than two weeks. But in that time, they appear able to influence the host immune system and stop it attacking tissue and organs.
Previous trials have shown that TSO can stimulate response and remission in patients with inflammatory bowel disease.
Bobby W Sandage Jr, President and CEO of Coronado Biosciences Inc, of Burlington, Massachusetts, the company behind the new treatment, told the press:
"This Phase 2 study will expand our understanding of TSO's clinical usefulness in patients with moderately to severely active Crohn's disease."
The company is developing TSO as a biologic treatment for autoimmune diseases, such as Crohn's disease, ulcerative colitis and multiple sclerosis.
In a statetement, Coronado said it chose TSO "as the biological agent of choice because it is not a human pathogen and is spontaneously eliminated from the body within several weeks after dosing".
It is also developing another biologic, called CND0-109, that activates natural killer (NK) cells, for the treatment of acute myeloid leukemia (AML) and solid tumors.
The TRUST-I TrialTRUST-I is a randomized, double-blind, placebo-controlled trial that is taking place at a number of US centers and is designed to test the safety and effectiveness of TSO in patients with Crohn's disease.
The team aims to enrol about 220 patients with the disease who will take either a dose of the active drug or a placebo by mouth once every two weeks for 12 weeks.
One dose of TSO will contain 7,500 parasite eggs harvested from pig feces, suspended in a tablespoon of saline, ready for swallowing.
The main point of the trial is to test whether the treatment produces a response, as measured by the Crohn's Disease Activity Index (CDAI), with induction of remission being a secondary measure.
The company said it expects the trial to finish in the second half of 2013.
A parallel trial will take place in Europe, run by Coronado's German development partner for TSO in Crohn's disease, Dr. Falk Pharma GmbH. That will also be a multi-center, phase 2, double-blind, randomized, placebo-controlled trial.
Coronado recently reported positive results from a phase 1 trial of TSO in patients with Crohn's disease, where the biologic was shown to be "safe and well- tolerated". That trial was a multi-center, double-blind, placebo-controlled study of 36 patients with Crohn's disease that tested escalating doses of the drug.
Hygiene HypothesisUsing TSO to treat Crohn's disease and other autoimmune disorders is based on a theory called the Hygiene Hypothesis that suggests having little exposure to parasites somehow prevents proper immune system regulation in people who live in developed countries with "cleaner environments".
Karin Hehenberger, Coronado's Executive Vice President & Chief Medical Officer, says epidemiologic studies, as well as pre-clinical data in different disease models, show autoimmune diseases are less prevalent in people with parasitic worm colonies, supporting the idea of an "inverse relationship" between such diseases and colonization by such parasites.
An evidence-based systematic review on the management of IBD that was published in the The American Journal of Gastroenterology in April 2011, said the link between higher risk of IBD in people living in "cleaner environments", as suggested by the "hygiene hypothesis", means we need to better understand the immune system and gut flora as causes of the disease.
Written by Catharine Paddock PhD