5B5 A Phase II Trial of Single-Dose Oral ETX0914 (AZD0914) for Treatment of Uncomplicated Urogenital Gonorrhea

Friday, September 23, 2016: 9:00 AM
Salon B
Stephanie N. Taylor, MD1, Jeanne Marrazzo, MD, MPH2, Byron Batteiger, MD3, Ned Hook III, MD4, Arlene C. Sena, MD, MPH5, Michael Wierzbicki, PhD6, Hannah Kwak, BS7, Shacondra Johnson, BSPH8, Kenneth Lawrence, PharmD9 and John Mueller, PhD9, 1Section of Infectious Diseases, Louisiana State University Health Sciences Center, New Orleans, LA, 2Division of Infectious Diseases, University of Alabama Birmingham, Birmingham, AL, 3Division of Infectious Diseases, Indiana University School of Medicine, Indianapolis, IN, 4Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, 5Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, 6Biostatistics, EMMES Corporation, Rockville, MD, 7Biostatistics, Emmes Corporation, Rockville, MD, 8FHI 360, Durham, NC, 9Clinical Development, Entasis Therapeutics, Waltham, MA

Background:  The Centers for Disease Control and Prevention described antibiotic-resistant Neisseria gonorrhoeae (NG) as an urgent public health threat and recommended the development of new therapies.  ETX0914 is a novel spiropyrimidinetrione antibiotic that unlike any marketed antibiotic, inhibits deoxyribonucleic acid biosynthesis by accumulation of double strand cleavages. In this multi-center Phase II trial, we evaluated ETX0914 for treatment of uncomplicated urogenital (urethral/cervical) gonorrhea in men and women.

Methods:  Individuals with signs and symptoms of urogenital gonorrhea, confirmed urogenital gonorrhea in the past 14 days or who had sexual contact with an individual diagnosed with gonorrhea in the past 14 days were eligible for enrollment. Participants were randomized approximately 70:70:40 to receive either 2000mg or 3000mg ETX0914 orally or 500mg ceftriaxone in a single intramuscular injection. A test-of-cure visit occurred at 6+2 days to evaluate microbiological cure by culture, clinical cure and safety. A follow-up safety visit also occurred at 31+2 days. The primary efficacy outcome measure was the microbiological cure rate for uncomplicated urogenital gonorrhea at the test-of-cure visit.

Results: A total of 179 participants (167 men and 12 women) were enrolled, randomized, and treated from November 2014 through December 2015. At baseline, 141 (79%) had positive urogenital cultures for NG (132 urethral and 9 cervical). In the per protocol population, 48/49 (98%) participants in the ETX0914 2000mg arm, 47/47 (100%) in the ETX0914 3000mg arm, and 21/21 (100%) in the ceftriaxone arm achieved microbiological cure. ETX0914 was well tolerated with only 21/179 (12%) participants reporting 20 mild AEs and 1 moderate AE. The most common ETX0914-related AEs were gastrointestinal.

Conclusions: Single-dose oral ETX0914 was safe and effective in eradicating NG from urogenital sites and shows promise for treatment of uncomplicated gonorrhea.