The overall goal of this application is to develop and implement a small pilot study to validate the potential of SQ109 for treatment of Helicobacter pylori infections. SQ109 is a small molecule drug candidate currently in phase 2 clinical trials fo treatment of adult pulmonary tuberculosis (TB). SQ109 is also active against H. pylori in vitro, and we filed an Investigational New Drug (IND) application with the FDA for this new indication in Oct 2010. H. pylori infection of gastric epithelium is the most common bacterial infection in th world.1,2 Ten to 20% of H. pylori-infected individuals eventually develop peptic ulcer disease.4-6 Standard therapy is currently a regimen of 2 to 4 antibiotics administered for up to 14 days with a proton pump inhibitor or an oral bismuth preparation. This regimen, despite the number of drugs, has only a 75%-80% success rate, underscoring the need for new more efficacious and faster-acting drugs for treatment of H. pylori infection. Preclinical studies of orally-administere SQ109 document its presence in stomach tissues as well as stomach contents for up to 5 hr, and SQ109 rapidly (within 4 hr) kills >>99% of H. pylori in vitro at concentrations achievable in stomach. Animal models, such as the Mongolian gerbil or mouse, are inappropriate to evaluate new antibiotics against H. pylori infection, since the former is an H. pylori-related adenocarcinoma model, and the latter is a model to test candidate vaccines. Neither animal model has been used extensively to evaluate new antibiotics. Orally administered SQ109 was safe and well-tolerated in phase 1 studies in healthy volunteers, and a phase 2a study in patients with pulmonary TB. We propose to evaluate the safety, tolerance, and preliminary efficacy of SQ109 in patients with H. pylori infection using a validated and FDA-approved clinical endpoint, the UBT.
SPECIFIC AIM 1. CONDUCT A PILOT CLINICAL STUDY TO EVALUATE SQ109 TREATMENT OF H. PYLORI INFECTION.
SPECIFIC AIM 2. EVALUATE THE ACTIVITY OF SQ109 AGAINST A BANK OF H. PYLORI CLINICAL ISOLATES. The results of this work will be used to determine whether SQ109 should be evaluated in subsequent, well- powered phase 2 and registration-level phase 3 studies for treatment of H. pylori gastrointestinal infection. The criteria for moving this drug into formal clinical development for treatment of duodenal ulcers will be its ability to eliminate H. pylori (a negative UBT at 21 or 42 days).
H. pylori infection of gastric epithelium is the most common bacterial infection in the world, and the lifetime risk for developing ulcers is 3-10-fold higher i infected individuals. Existing drugs are inadequate for treatment of this infection, and in this application we propose to evaluate a new drug with great promise for this indication.