Controlled Human Infection Model Challenge/Rechallenge

NCT04992520 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: CVIA 088
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to better understand Shigella immunity. The study will compare the shigellosis rate in participants previously challenged with a different Shigella serotype to the attack rate in participants not previously exposed to Shigella (naive participants).

Conditions

Shigellosis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Shigellosis Following Shigella Challenge

  Shigellosis was defined as: * Severe diarrhea: ≥ 6 loose (grade 3-5) stools within 24 hours or \>800 - 999 g loose stools within any 24-hour window, or * Moderate diarrhea (4 - 5 loose stools within 24 hours or 401-800 g loose stools within any 24-hour window) with fever (oral temperature of ≥ 101.2°F / 38°C) OR with ≥ 1 moderate constitutional or enteric symptom OR ≥ 2 episodes of vomiting in a 24-hour period, or * Dysentery: ≥ 2 loose stools with gross blood (hemoccult positive) in 24 hours AND fever OR ≥ 1 moderate constitutional/enteric symptom OR ≥ 2 episodes of vomiting in 24 hours. Constitutional/Enteric symptoms include nausea, abdominal cramps/pain, myalgia, arthralgia, or malaise. Stools were graded on the following scale: * Grade 1, firm formed; * Grade 2, soft formed; * Grade 3, viscous opaque liquid or semi-liquid; * Grade 4, watery opaque liquid; * Grade 5, clear watery or mucoid liquid. Outcome data were evaluated by an independent, blinded adjudication board.

  8 days after challenge administration (Days 1-8 and Days 90-97 for challenge 2)

Secondary Outcomes (11)

• Maximum Volume of Loose Stools in Any 24-hour Period

  8 days after challenge administration (Days 1-8 and Days 90-97 for challenge 2)

• Percentage of Participants With Severe Diarrhea

  8 days after challenge administration (Days 1-8 and Days 90-97 for challenge 2)

• Percentage of Participants With Diarrhea of Any Severity

  8 days after challenge administration (Days 1-8 and Days 90-97 for challenge 2)

• Total Weight of Grade 3-5 Stools Per Participant After Challenge

  8 days after challenge administration (Days 1-8 and Days 90-97 for challenge 2)

• Percentage of Participants With Nausea, Vomiting, Anorexia, Abdominal Pain/Cramps Rated as Moderate to Severe

  8 days after challenge administration (Days 1-8 and Days 90-97 for challenge 2)

Study Arms (6)

Group 1A: S. sonnei 53G

EXPERIMENTAL

Naïve participants were challenged with 1500 colony forming units (CFU) of S. sonnei strain 53G.

Biological: Shigella sonnei 53G

Group 1B: S. flexneri 2a 2457T (Naive)

EXPERIMENTAL

At least 3 months after the challenge in Group 1A, newly recruited naïve participants were challenged with 1500 CFU of S. flexneri 2a strain 2457T.

Biological: Shigella flexneri 2a 2457T

Group 1B: S. Flexneri 2a (Veteran)

EXPERIMENTAL

At least 3 months after challenge with S. sonnei 53G in Group 1A, participants received a 2nd challenge with 1500 CFU of S. flexneri 2a strain 2457T.

Biological: Shigella flexneri 2a 2457T

Group 2A: S. Flexneri 2a

EXPERIMENTAL

Naïve participants were challenged with 1500 CFU of S. flexneri 2a strain 2457T.

Biological: Shigella flexneri 2a 2457T

Group 2B: S. Sonnei 53G (Naive)

EXPERIMENTAL

At least 3 months after the challenge in Group 2A, newly recruited naïve participants were challenged with 1500 CFU of S. sonnei 53G.

Biological: Shigella sonnei 53G

Group 2B: S. Sonnei 53G (Veteran)

EXPERIMENTAL

At least 3 months after challenge with S. flexneri 2a in Group 2A, participants received a 2nd challenge with 1500 CFU of S. sonnei 53G.

Biological: Shigella sonnei 53G

Interventions

Shigella sonnei 53G BIOLOGICAL

Shigella sonnei (S. sonnei) strain 53G (Lot 1794); Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast.

Group 1A: S. sonnei 53G; Group 2B: S. Sonnei 53G (Naive); Group 2B: S. Sonnei 53G (Veteran)

Shigella flexneri 2a 2457T BIOLOGICAL

Shigella flexneri (S. flexneri) strain 2457T (Lot 1617); Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast.

Group 1B: S. Flexneri 2a (Veteran); Group 1B: S. flexneri 2a 2457T (Naive); Group 2A: S. Flexneri 2a

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adults, male or female, aged 18 to 50 years (all inclusive) at the time of enrollment.
• General good health, without clinically significant medical history, physical examination findings, or clinical laboratory abnormalities per judgment of Principal Investigator (PI).
• Willingness to participate in the study after all aspects of the protocol have been explained and written informed consent obtained.
• Completion of a training session and demonstrated comprehension of the protocol procedures and knowledge of Shigella-associated illness by passing a written examination (70% passing score).
• Availability for the study duration, including all planned follow-up visits.
• Female participants must have a negative pregnancy test at screening and prior to each challenge.
• Female participants must agree to avoid pregnancy for 29 days following the last challenge dose by use of an efficacious hormonal or barrier method of birth control during the study. Abstinence is acceptable. Female participants unable to bear children must have this documented (e.g., tubal ligation or hysterectomy).
• Willingness to refrain from participation in a study of another investigational agent for 90 days following the last challenge dose.

You may not qualify if:

• Presence of a significant medical or psychiatric condition that in the opinion of the investigator precludes participation in the study. Some medical conditions that are adequately treated and stable would not preclude entry into the study.
• Clinically significant abnormalities in screening on physical exam or screening laboratory results as determined by PI or PI in consultation with the research monitor and Sponsor.
• Recent receipt of another investigational product (within 30 days before enrollment).
• Positive enzyme-linked immunosorbent assay (ELISA) and confirmatory tests for human immunodeficiency virus (HIV).
• Positive hepatitis C (HCV) ELISA and confirmatory test (e.g., HCV ribonucleic acid (RNA)).
• Positive hepatitis B virus surface antigen (HBsAg) by ELISA.
• Use of any medication that affects immune function (e.g., corticosteroids and others) within 30 days preceding the first challenge or planned use during the active study period (topical and ophthalmologic steroids are allowable).
• Evidence of impaired immune function or immune compromise (known immunodeficiency syndrome; either congenital, acquired, or iatrogenic; active autoimmune disease; repeated serious infections without known cause).
• Immunoglobulin A (IgA) deficiency (serum IgA \< 7 mg/dL or below the limit of detection of the assay).
• Positive blood test for human leukocyte antigen (HLA)-B27.
• Personal or family history of an inflammatory arthritis.
• Currently pregnant or nursing.
• Have household contacts who are \< 2 years old or \> 80 years old or infirm or immunocompromised.
• Employment as a health care worker with direct patient care, in a daycare center (for children or the elderly), or direct food handler; includes individuals who work directly with food in commercial establishments.
• Evidence of current alcohol or drug dependence, or history of dependence in the last 6 months.

Sponsors & Collaborators

• PATH: lead
• United States Department of Defense: collaborator
• Johns Hopkins University Center for Immunization Research (CIR): collaborator

Study Sites (1)

Center for Immunization Research (CIR) at Johns Hopkins School of Public Health (JHSPH)

Baltimore, Maryland, 21224, United States

Location

MeSH Terms

Conditions

Dysentery, Bacillary

Condition Hierarchy (Ancestors)

Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Dysentery; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Results Point of Contact

• Title: Patricia Njuguna/Senior Medical Officer
• Organization: PATH

pnjuguna@path.org

+254 20 3877177

Study Officials

• Kawsar Talaat, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2021
• First Posted: August 5, 2021
• Study Start: April 26, 2022
• Primary Completion: August 29, 2023
• Study Completion: August 29, 2023
• Last Updated: January 31, 2025
• Results First Posted: January 31, 2025

Record last verified: 2024-12

Locations

US (1)