Safety and Tolerability of ShigActive™, a Shigella spp. Targeting Bacteriophage Preparation, in a Phase 1 Randomized,...

Area of Science:

• Microbiology
• Gastroenterology
• Clinical Trials

Background:

• Shigella species cause significant global morbidity and mortality, particularly in children, with limited conventional treatment options.
• Shigellosis, a severe diarrheal disease, presents challenges for prevention and treatment due to antimicrobial resistance and vaccine limitations.
• Bacteriophage therapy offers a potential alternative for treating bacterial infections, including those caused by Shigella.

Purpose of the Study:

• To evaluate the safety and tolerability of ShigActive™, a bacteriophage preparation targeting Shigella spp.
• To assess adverse events and potential impacts on gastrointestinal inflammatory mediators and the fecal microbiome.
• To establish the feasibility of ShigActive™ as a therapeutic agent in a human clinical setting.

Main Methods:

• A randomized, placebo-controlled, double-blind Phase 1 clinical trial was conducted.
• Ten participants received ShigActive™ or placebo orally with sodium bicarbonate for 7 days.
• Adverse events, inflammatory markers, and microbiome changes were monitored over 90 days.

Main Results:

• Fifty percent of ShigActive™ recipients reported mild gastrointestinal symptoms; one experienced moderate fatigue.
• No serious or medically attended adverse events were observed up to day 90.
• No significant differences in inflammatory mediators or fecal microbiome composition were detected between groups or from baseline.

Conclusions:

• The first-in-human trial demonstrates that ShigActive™ is safe and well-tolerated when administered orally.
• ShigActive™ shows no significant adverse effects compared to placebo, supporting its potential as a shigellosis treatment.
• Further research is warranted to explore the efficacy of ShigActive™ in treating shigellosis.