Safety and Tolerability of ShigActive™, a <i>Shigella</i> spp. Targeting Bacteriophage Preparation, in a Phase 1 Randomized, Double-Blind, Controlled Clinical Trial
Wilbur H. Chen,
Joelle Woolston,
Silvia Grant-Beurmann,
Courtney K. Robinson,
Garima Bansal,
Joseph Nkeze,
Jasnehta Permala-Booth,
Claire M. Fraser,
Sharon M. Tennant,
Mallory C. Shriver,
Marcela F. Pasetti,
Yuanyuan Liang,
Karen L. Kotloff,
Alexander Sulakvelidze,
Jennifer A. Schwartz
Affiliations
Wilbur H. Chen
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Joelle Woolston
Intralytix, Inc., Columbia, MD 21046, USA
Silvia Grant-Beurmann
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Courtney K. Robinson
Intralytix, Inc., Columbia, MD 21046, USA
Garima Bansal
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Joseph Nkeze
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Jasnehta Permala-Booth
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Claire M. Fraser
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Sharon M. Tennant
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Mallory C. Shriver
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Marcela F. Pasetti
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Yuanyuan Liang
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Karen L. Kotloff
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Bacterial diseases of the gastrointestinal (GI) tract continue to be a major worldwide cause of human morbidity and mortality. Among various enteric pathogens, Shigella spp. are some of the most common and deadly bacterial pathogens. They are responsible for ~125 million worldwide cases of shigellosis, and ~14,000 deaths annually, the majority in children under the age of 5 and occurring in developing countries. Preventing and treating shigellosis with conventional drugs (e.g., vaccines and antibiotics) has proven to be very difficult. Here, we assessed the safety and tolerability of ShigActive™, a lytic bacteriophage preparation targeting Shigella spp., in a randomized, placebo-controlled, double-blind Phase 1 clinical trial. Ten participants randomized 4:1 received ShigActive™ or placebo co-administered with sodium bicarbonate orally three times daily for 7 days. Solicited and unsolicited adverse events (AEs) were observed for 29 days. Fifty percent of the subjects receiving ShigActive™ reported mild GI-related symptoms, while one participant experienced moderate fatigue. No serious or medically attended AEs occurred through day 90. Additionally, no significant differences in GI-associated inflammatory mediators or fecal microbiome changes were observed between placebo- and ShigActive™-treated subjects, or from a participants’ baseline value. The results of this first-in-human (FIH) randomized, controlled Phase 1 trial of ShigActive™ demonstrate that it is safe and well tolerated when orally administered with no significant differences compared to placebo controls.
