Celiacs needed for medication research study

Okanagan Clinical Trials press release

Okanagan Clinical TrialsAdults with Celiac Disease are invited to participate in an ongoing research study with Okanagan Clinical Trials examining an investigational possible treatment for this disorder.

Celiac Disease is an autoimmune disorder, which damages the small intestine and affects its ability to absorb nutrients from food. Currently, the only management available for this condition is strict adherence to a gluten-free diet – in which all products with wheat or a variety of other grains are off limits.

“Avoiding gluten is very difficult for patients and having to live on a gluten-free diet is restrictive and can definitely affect your quality of life,” says Dr. Sally Godsell, investigator for Okanagan Clinical Trials. “If it is possible to develop a new medicine for this condition, which could help patients reduce their signs and symptoms, it would make a big difference for a lot of people.”

Celiac Disease affects 1% of the population or about ~346,890 people in Canada, ~3 million people in the United States and it occurs in individuals who are genetically susceptible. Gluten, a protein found in grains such as wheat, rye and barley, triggers an immune response in the body that damages the mucosal lining of the small intestine.

If left unmanaged, Celiac Disease can cause chronic intestinal damage and increased risk for a variety of disorders included iron deficiency anemia, osteoporosis, vitamin deficiencies, nervous system disorders, pancreatic insufficiency, lactose intolerance, intestinal lymphomas and other gastrointestinal cancers.

The current research study at Okanagan Clinical Trials is examining an investigational medication that is now being tested for its effectiveness and tolerability in Celiac Disease.

In order to meet research study criteria, volunteers must be between the ages of 18 and 75, and diagnosed with Celiac Disease by biopsy and blood test 12 months or more before research study entry.  Volunteers must also have attempted a gluten-free diet for 12 months or longer and are still experiencing gastrointestinal symptoms when exposed to gluten.

More than 320 patients at 60 centers across the United States and Canada will participate in this research study. Okanagan Clinical Trials was selected to participate because of its proven track record in conducting clinical trials since 1992.

Effects will be measured over a 20 week period and will not affect regular medical coverage. Participants are free to leave the research study at any time.

For more information see: Celiac Disease Clinical Trial Invitation Letter

or visit www.okanaganclinicaltrials.com 

Alvine announces positive results for anti-gluten drug phase 2a trial

Press Release

Alvine Pharmaceuticals, Inc. has announced positive results from its Phase 2a clinical trial of ALV003, which demonstrated the ability of ALV003 to attenuate gluten-induced intestinal mucosal injury in serologically negative celiac disease patients maintained on a gluten-free diet for one or more years.  The study findings will be presented in a late breaking oral session at the 19th United European Gastroenterology Week (UEGW) in Stockholm on October 24.  The full abstract (#OP050B) can currently be accessed on the UEGW website at http://www.uegw11.uegf.org.

“There are currently no approved therapies for celiac disease.  Strict, life-long adherence to a gluten-free diet (GFD) is the current standard of care and the only treatment option for these patients, but this does not offer a comprehensive solution,” said Peter Green, M.D., director of The Celiac Disease Center and professor of clinical medicine at Columbia University College of Physicians and Surgeons .  “A GFD does not completely prevent exposure to gluten and does not affect the underlying cause of disease, potentially leaving patients vulnerable to gastrointestinal symptoms and serious long-term medical consequences.”

Phase 2a Trial Design and Results

In the double-blind, placebo-controlled Phase 2a clinical trial, 41 well-controlled, well-characterized adult celiac disease patients were randomized to receive ALV003 or placebo daily for six weeks at the time of ingestion of 2g of gluten (bread crumbs). Study participants underwent small bowel biopsy at the beginning of the trial and after being given the daily gluten challenge for six weeks. The primary endpoint was intestinal villus morphometry (Villus height: Crypt depth, or Vh:Cd) measured at baseline and at six weeks. Secondary endpoints included intraepithelial lymphocyte (IEL) density, gastrointestinal symptoms as measured by Gastrointestinal Symptom Rating Scale (GSRS) scores, celiac serologies, safety and tolerability.

Biopsy results from 34 evaluable patients with celiac disease showed that there was significantly less small intestinal mucosal injury in patients treated with ALV003 than in placebo-treated patients at six weeks (p=0.013).  In addition, the data showed statistically significant differences in changes in IEL and both α/β and γ/δ T-lymphocyte subsets.

GSRS scores were directionally consistent with the morphologic changes in the intestinal mucosa (i.e., with less intestinal mucosal injury there was a directionally consistent lower GSRS score). No significant changes were observed in the celiac serology tests.  Adverse events consistently occurred more frequently in the placebo-treated patients. Adverse events that occurred in 10 percent or more patients included abdominal distension, flatulence, eructation, abdominal pain and diarrhea.

“Based on the results of this rigorously conducted trial, we believe that clinical proof-of-principle has been achieved.  We are currently preparing for a Phase 2b trial of ALV003 in celiac disease patients targeted to begin in 2012,” said Daniel Adelman, chief medical officer at Alvine Pharmaceuticals.

UEGW Data Presentation and Conference Call Information

The abstract, titled “ALV003, a Novel Glutenase, Attenuates Gluten-Induced Small Intestinal Mucosal Injury in Celiac Disease Patients: A Randomized Controlled Phase 2A Clinical Trial,” will be presented on Monday, October 24, at 2:12 p.m. CEST during the Free Paper Session: Late breaking news in Hall K1/2 by Dr. Markku Mäki, chair and professor of pediatrics at the University of Tampere and Tampere University Hospital in Finland, and lead investigator of the ALV003 Phase 2a trial.

Alvine will host a conference call and webcast to discuss these data and the overall celiac disease space. In addition to Alvine management, Dr. Peter Green will also participate in the conference call. The call will be held Thursday, October 27, at 10:00 a.m. Pacific Time (PT)/1:00 p.m. Eastern Time (ET). The live event will be available from Alvine’s website at http://www.alvinepharma.com, under the News and Media section, or by calling (866) 582-8907 (domestic) or (678) 825-8232 (international). The access code is 15752879.  A replay of the webcast will be available from Alvine’s website.

About ALV003

ALV003 is an orally administered mixture of two recombinant gluten-specific proteases, a cysteine protease (EP-B2) and a prolyl endopeptidase (PEP).  ALV003 targets gluten and degrades it into small fragments, which, in vitro, diminishes immunogenicity.  ALV003 is being developed as a potential treatment for celiac disease patients in conjunction with a gluten-free diet and is currently in Phase 2 clinical development.

About Alvine

Alvine Pharmaceuticals, Inc. is a private, clinical-stage, specialty biopharmaceutical company located in San Carlos, Calif., focused on the development of biologics targeting autoimmune and inflammatory diseases, including celiac disease.  Alvine is focusing clinical development efforts on ALV003, an investigational drug in Phase 2 trials that could potentially be the first approved therapeutic treatment for patients with celiac disease.  For additional information about the company, please visithttp://www.alvinepharma.com.

Treatments Under Development For Celiac Disease

L.A. Times reporter Cathryn Delude has written a great summary article of the efforts underway to develop treatments for Celiac Disease. You can find the full article in the December 21st edition called “New hope for Celiac Disease“.

She writes that there are two categories of treatments being developed:

1. Enzyme therapy, that would supplement a gluten-free diet and protect patients from occasional gluten exposure, and;

2. Immunotherapy, that would train the immune system to tolerate gluten and allow one to eat a regular diet.

Here’s a quick summary of the article.

Enzyme therapy uses oral enzymes that target gluten. Humans cannot completely digest gluten as we lack the digestive enzymes to break it down. Stanford researchers are combining enzymes from bacteria and barley to finish this digestion. Tests in rats proved to be promising. Alvine Pharmaceuticals is now recruiting patients for a Phase II clinical trial. Phase II trial testing of a different enzyme therapy drug, Larazotide, by Alba Therapeutics, is almost complete.

Immunotherapy is proported to allow Celiacs to eat a regular diet by quelling T-cell immune response. A company, Nexpep, is packaging the gluten peptides that trigger the immune response in a vaccine delivered under the skin to desensitize the immune reaction. Testing is said to have worked well in animals. Phase I safety trials of the vaccine, Nexvax2, will be completed in mid-2010.

Some of you may have also heard of the hook worm approach. This is where a hookworm is put in the gut to relieve asthma. Researchers have now tested it on 20 patients with celiac disease to see if they have benefits from it as a low-tech immunotherapy. The results haven’t been published but all the patients in the trial refused medication that would kill the parasites after the trial was complete.