Phase III Trials Evaluate Antibiotic Candidate Eravacycline
Investigational treatment targets multidrug-resistant infections
Tetraphase Pharmaceuticals has provided a clinical update on its phase III global clinical trial program IGNITE (Investigating Gram-Negative Infections Treated With Eravacycline).
Eravacycline is being developed as a broad-spectrum antibiotic to treat multidrug-resistant (MDR) infections, including those caused by many of the MDR Gram-negative bacteria identified as urgent public health threats by the Centers for Disease Control and Prevention in September 2013.
Fifty percent of targeted enrollment has been achieved in the IGNITE 1 trial, which was initiated in late August 2013 to investigate the safety and efficacy of eravacycline in the treatment of complicated intra-abdominal infections (cIAIs). Enrollment has also been initiated in the IGNITE 2 study, a two-part phase III clinical trial evaluating the safety and efficacy of intravenous (IV) and oral formulations of eravacycline for the treatment of complicated urinary tract infections (cUTIs).
Data from the lead-in portion of the IGNITE 2 study are expected in mid-2014, top-line data from IGNITE 1 in the first quarter of 2015, and top-line data from IGNITE 2 in mid-2015. Tetraphase plans to file for U.S. regulatory approval of eravacycline for both indications by the end of 2015.
IGNITE 1 is a randomized, double-blind, double-dummy, global phase III clinical trial designed to assess the efficacy and safety of eravacycline (1.0 mg/kg every 12 hours) compared with ertapenem (1 g every 24 hours) in the treatment of cIAIs. The study is designed to enroll 536 adult patients in approximately 100 centers worldwide. The study’s primary endpoint is the clinical response at the test-of-cure (TOC) visit in the microbiological intent-to-treat (micro-ITT) patient population in the two treatment arms.
The study is also comparing the microbiologic responses in the treatment arms at the end of treatment and at TOC visits in the micro-ITT and microbiologically evaluable populations. TOC visits take place 25 to 31 days after the initial dose of eravacycline. The follow-up visit is conducted 38 to 50 days after the initial dose of eravacycline.
IGNITE 2 is a randomized, double-blind, phase III clinical trial designed to assess the efficacy and safety of eravacycline compared with levofloxacin in the treatment of cUTIs at approximately 150 clinical trial sites worldwide. The two-part study includes a lead-in phase, in which approximately 120 patients will be randomly assigned to receive eravacycline in one of two IV-to-oral step-down dosing cohorts (1.5 mg/kg IV every 24 hours followed by 200 or 250 mg orally every 12 hours) or levofloxacin (750 mg IV every 24 hours followed by 750 mg orally every 24 hours). The two eravacycline oral dosing regimens were determined based on the results of a phase 1 oral pharmacokinetic trial, which indicated acceptable plasma drug levels and tolerability in healthy subjects at the 200-mg and 250-mg twice-daily dose levels.
Under the planned trial protocol, after treatment of the 120 patients in the lead-in portion of the trial, an evaluation of primary efficacy, safety, and tolerability endpoints will be conducted in a planned interim analysis to determine the dose regimen to be carried forward into the second portion of the study. An additional 720 patients will then be enrolled and randomly assigned to receive the selected dose regimen of eravacycline or levofloxacin.
This 720-patient study is designed to be a non-inferiority (10% margin) trial, with a primary endpoint of clinical and microbiological responses approximately 7 days after the completion of treatment.
Source: Tetraphase Pharmaceuticals; March 20, 2014.