A Phase 1/2a Double-Blind, Randomized, Placebo-Controlled Trial to Assess the Safety and Efficacy of Oral Administration of the Bacteriophage Preparation, ShigActive™, in a Human Experimental Model of Shigellosis With Shigella Flexneri 2a Strain
Overview
- Phase
- Phase 1
- Intervention
- Placebo
- Conditions
- Shigellosis
- Sponsor
- Intralytix, Inc.
- Enrollment
- 52
- Locations
- 1
- Primary Endpoint
- Phase 1: Number and Severity of Solicited and Unsolicited Adverse Reactions
- Status
- Active, not recruiting
- Last Updated
- 10 months ago
Overview
Brief Summary
The study is a first-in-human Phase 1/2a randomized, double-blind, placebo-controlled trial to assess the clinical safety and efficacy of ShigActive in healthy adults with experimental Shigella challenge.
Detailed Description
The purpose of this study is to determine if ShigActive is safe and effective in healthy adults in a continuous Phase 1/2a trial. Phase 1 will asses the safety of ShigActive in healthy adults, while Phase 2a will evaluate the safety and efficacy of ShigActive in healthy adults after a challenge with Shigella. ShigActive is a collection of bacteriophages. Bacteriophages (or phages) are viruses that infect only bacteria. The phages in ShigActive infect a specific type of bacteria called Shigella, which is the causative agent of shigellosis or dysentery. ShigActive is intended to significantly reduce or eliminate Shigella levels in the human gastrointestinal tract, which in turn, is anticipated to reduce the incidence and/or severity of shigellosis.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age 18 to 50 years.
- •Access to CVD clinical site and available and willing to be followed for the planned duration of the study, including all follow-up visits.
- •Able and willing to provide informed consent.
- •Willing to participate after all aspects of trial explained.
- •Assessment of understanding:
- •Volunteer demonstrates understanding of this study;
- •Completes a questionnaire prior to first treatment with verbal demonstration of understanding of all questionnaire items answered incorrectly;
- •Receives a passing score of 70% or higher on the Comprehension Assessment Tool.
- •Agrees not to enroll in another study of an investigational research agent during the study, with the exception of potentially life-saving or COVID-19-related experimental treatments.
- •Good general health as shown by medical history, physical exam, and screening laboratory tests or clinical laboratory abnormalities per clinical judgment of the PI.
Exclusion Criteria
- •Blood products received within 120 days before first treatment.
- •Investigational research agents received within 30 days before first treatment.
- •Body mass index (BMI) less than 19.0 kg/m2 or greater than 36.0 kg/m
- •Pregnant or breastfeeding.
- •Poor venous access, as defined by inability to obtain venous blood after 3 venipuncture attempts.
- •Persons whose occupation involves the handling of ETEC, cholera, or Shigella bacteria.
- •Regular (one time per week or more) use of antidiarrheals, stool softeners, laxatives, antacids, or other agents to lower stomach acidity.
- •Use of oral or IV antimicrobials within 2 weeks of study start or planned use during active study phase.
- •Proton pump inhibitors, H2 blockers or antacids within 48 hours prior to dosing or planned use during active study phase.
- •Abnormal bowel patterns, defined by \<3 stools per week or \>2 stools per day on average over the past 6 months.
Arms & Interventions
Placebo
Dose is 1mL of placebo given orally three times a day for 7 days (Phase 1) or 6 days (Phase 2a)
Intervention: Placebo
Bacteriophage
Dose is 1mL of bacteriophage preparation given orally three times a day for 7 days (Phase 1) or 6 days (Phase 2a)
Intervention: bacteriophage
Outcomes
Primary Outcomes
Phase 1: Number and Severity of Solicited and Unsolicited Adverse Reactions
Time Frame: Up to Day 90
Number of subjects reporting solicited and unsolicited AEs, laboratory measures of safety, and adverse (up to Day 29) and serious adverse events (up to Day 90) following treatment with ShigActive or placebo
Phase 2a: Number of Solicited and Unsolicited Adverse Reactions
Time Frame: Up to Day 90
Number of subjects reporting solicited and unsolicited AEs, laboratory measures of safety, and adverse (up to Day 29) and serious adverse events (up to Day 90) following treatment with ShigActive or placebo
Phase 2a: Onset of Clinical Shigellosis Post-Challenge
Time Frame: Day 2 to Day 7 (Post-Challenge)
Clinical shigellosis with onset during Day 2 to Day 7 post-challenge, defined as fever, diarrhea, and/or dysentery
Secondary Outcomes
- Phase 2a: Onset of Moderate-to-Severe Shigellosis Post-Challenge(Day 2 to Day 7 (Post-Challenge))
- Phase 2a: Severity of Shigellosis Symptoms(Day 2 to Day 7 (Post-Challenge))
- Phase 2a: Number of Shigella Organisms Secreted in Stool(Up to Day 15)