Phase 3 IGNITE4 trial to examine safety, efficacy of IV eravacycline in cIAIs

Tetraphase Pharmaceuticals recently launched IGNITE4 — a randomized, double blind, phase 3 trial examining the safety and efficacy of IV eravacycline compared with meropenem in patients with complicated intra-abdominal infections — according to a company press release.

Eravacycline (Tetraphase Pharmaceuticals) is a fully-synthetic tetracycline antibiotic with activity against multidrug-resistant pathogens, including carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii and colistin-resistant bacteria carrying the mcr-1 gene.

For the trial, researchers will compare twice-daily eravacycline dosed at 1 mg/kg every 12 hours with meropenem dosed at 1 g every 8 hours in patients with complicated intra-abdominal infections (cIAIs). Researchers expect to enroll approximately 450 patients from 75 centers worldwide, according to the release. The primary endpoint is clinical response at the test-of–cure visit, which is 25 to 31 days following the initial dose. The noninferiority margin will be set at 12.5%.

To date, eravacycline has been assessed in more than 1,300 patients with cIAIs and complicated urinary tract infections (cUTIs) and has completed two phase 3 trials — IGNITE1 and IGNITE2.

In the IGNITE1 trial, twice-daily IV eravacycline was well-tolerated and noninferior to ertapenem in patients with cIAIs, including those with resistant pathogens. The overall cure rates were 86.8% with eravacycline and 87.6% with ertapenem. Eravacycline also was effective in certain high-risk groups, including patients aged 65 years and older (88.6% vs. 89.3%), those with more severe disease (87.2% vs. 82.7%) and patients with one or more abscesses (87% vs. 86.4%).

In the IGNITE2 trial, an IV-to-oral regimen of eravacycline was inferior to IV-to-oral levofloxacin among patients with cUTIs (60.4% vs. 66.9%; difference, –6.5% [95% CI, –14.1 to 1.2]), according to data presented at ASM Microbe 2016. However, researchers noticed higher response rates among patients who stayed on IV eravacycline compared with those who switched. In a subgroup analysis of microbiological intent-to-treat patients who only received IV therapy, eravacycline response rates met the primary post-treatment endpoint (54.4% vs. 42.2%; difference, 12.2% [95% CI, –5.7% to 29.3%]), and the treatment continued to be more efficacious against levofloxacin-resistant pathogens. Another subgroup analysis examining independent risk factors for posttreatment visit failure linked receipt of IV drug for 3 or fewer days to poorer outcomes.

In the press release, Guy Macdonald, president and CEO of Tetraphase, said the company expects to see data from IGNITE4 in the fourth quarter of 2017. If successful, the results, along with data from IGNITE1, will be used to support a new drug application for IV eravacyline in cIAI.

Tetraphase Pharmaceuticals also plans to launch another phase 3 trial, IGNITE3, to assess once-daily IV eravacycline in patients with complicated cUTIs. In addition, the company continues to investigate an oral dose formulation in an ongoing phase 1 trial.

“Antibiotic resistance continues to be a growing public health threat and this critical issue is achieving attention on a global scale, most recently as an area of focus at the United Nations General Assembly,” Macdonald told Infectious Disease News. “We are committed to being part of the solution by working to develop new antibiotics, as we evaluate our phase 3 product candidate eravacycline as a potential new option for the treatment of both complicated urinary tract infections and complicated intra-abdominal infections.” – by Stephanie Viguers

References:

Tsai L, et al. Abstract L-834. Presented at: Interscience Conference on Antimicrobial Agents and Chemotherapy; Sept. 17-21, 2015; San Diego.

Tsai L, et al. Abstract L-835. Presented at: Interscience Conference on Antimicrobial Agents and Chemotherapy; Sept. 17-21, 2015; San Diego.

Tsai L, et al. Intravenous eravacycline with transition to oral therapy for treatment of complicated urinary tract infections including pyelonephritis: Results from a randomized, double-blind, multicenter, phase 3 trial (Ignite2). Presented at: ASM Microbe; June 16-20, 2016; Boston.

Tsai L, et al. Intravenous eravacycline compared to intravenous levofloxacin for the treatment of complicated urinary tract infections: Subgroup analysis from a randomized, double-blind, phase 3 trial (Ignite2). Presented at: ASM Microbe; June 16-20, 2016; Boston.

Tsai L, et al. Risk factors for change in microbiological outcomes between the end of therapy and post-treatment evaluations in patients with complicated uti treated with eravacycline: Analysis from a randomized, double-blind, multicenter, phase 3 trial (Ignite2). Presented at: ASM Microbe; June 16-20, 2016; Boston.

Disclosures: Macdonald is president and CEO of Tetraphase.