Date: 2014-10-06
Type of information: Initiation of patient enrollment
phase: 3
Announcement: initiation of patient enrollment
Company: Tetraphase Pharmaceuticals (USA - MA)
Product: eravacycline (7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline)
Action
mechanism: Eravacycline is a novel, fully synthetic tetracycline antibiotic with potent antibacterial activity against a broad spectrum of susceptible and multi-drug resistant bacteria. Eravacycline has demonstrated strong activity in vitro against Gram-positive pathogens, including both nosocomial and community-acquired methicillin susceptible or resistant Staphylococcus aureus strains, vancomycin susceptible or resistant Enterococcus faecium and Enterococcus faecalis, and penicillin susceptible or resistant strains of Streptococcus pneumoniae. In in vitro studies for cIAI, eravacycline consistently exhibited strong activity against enterococci and streptococci. One of the most frequently isolated anaerobic pathogens in cIAI, either as the sole pathogen or often in conjunction with another Gram-negative bacterium, is Bacteroides fragilis. In these studies eravacycline demonstrated activity against Bacteroides fragilis and a wide range of Gram-positive and Gram-negative anaerobes.
Disease: complicated urinary tract infections (cUTI)
Therapeutic area: Infectious diseases
Country:
Trial
details: The Phase 3 program called IGNITE (Investigating Gram-negative Infections Treated with Eravacycline) includes two studies, one for the treatment of complicated intra-abdominal infections (cIAI)(IGNITE 1) and one for the treatment of complicated urinary tract infections (cUTI)(IGNITE 2). IGNITE 2 is a two-part, randomized, multi-center, double-blind, Phase 3 clinical trial designed to assess the efficacy and safety of eravacycline compared with levofloxacin in the treatment of cUTI at approximately 150 clinical trial sites worldwide. The two-part trial features a recently completed lead-in portion which was designed to determine the dose regimen to be carried forward into the pivotal portion of the trial. For the pivotal portion, an additional 720 patients are expected to be enrolled and randomized 1:1 to receive eravacycline or levofloxacin (1.5 mg/kg intravenously every 24 hours followed by 200 mg orally every 12 hours) or levofloxacin (750 mg intravenously every 24 hours followed by 750 mg orally every 24 hours). This 720-patient portion of the trial is designed to be a non-inferiority (10% margin) study. The primary endpoint for the FDA is the responder outcome (a combination of clinical cure rate and microbiological response) in the Microbiological Intent-to-Treat (micro-ITT) Population at the Post-Treatment visit (defined as 6-8 days after the completion of therapy). For the EMA, the primary endpoint is the microbiological response in the micro-MITT and microbiologically evaluable populations at the Post Treatment visit. Top-line results from the pivotal portion of the study are expected to be available in mid-2015.
Latest
news: * On October 6, 2014, Tetraphase Pharmaceuticals announced initiation of patient enrollment in the pivotal portion of its IGNITE 2 Phase 3 clinical trial, a two-part trial studying the efficacy and safety of intravenous (IV) and oral formulations of eravacycline for the treatment of complicated urinary tract infections (cUTI). The company has selected the 200 mg eravacycline oral dose for the pivotal portion of the study after evaluating the positive results from the lead-in portion of the trial. As previously reported, in the lead-in portion of the trial, the IV-to-oral dosing regimen of eravacycline (1.5 mg/kg IV followed by 200 mg oral dose) compared favorably to levofloxacin, the comparator drug in the trial. The responder outcomes (FDA endpoint) for the IV-to-oral 200 mg and levofloxacin groups were 70.8% and 52.2%, respectively. The microbiological responses (EMA endpoint) were 75.0% and 56.5%, respectively. Overall, treatment was generally well tolerated in all groups, and the pharmacokinetics of the IV-to-oral 200 mg dose of eravacycline were comparable to the IV formulation. Tetraphase plans to present the full data from the lead-in portion of the IGNITE 2 Phase 3 trial at an upcoming scientific meeting. \"Initiation of the pivotal portion of the IGNITE 2 trial is an important milestone and we look forward to top-line data from the study in mid-2015,\" said Guy Macdonald, President and CEO of Tetraphase. \"We believe eravacycline is a differentiated antibiotic candidate given its potential as an IV-to-oral transition therapy and its activity against a wide variety of bacterial pathogens, including multidrug-resistant Gram-negative bacteria. IGNITE 2 is the second study in our IGNITE pivotal program, which also includes IGNITE 1, a Phase 3 clinical trial of an IV formulation of eravacycline in complicated intra-abdominal infections. We expect to announce top-line data from IGNITE 1 early in the first quarter of 2015.\" Tetraphase Pharmaceuticals expects to be able to file for U.S. regulatory approval for eravacycline for both indications by the end of 2015.
