Controlled Human Infection Model Challenge/Rechallenge

PATH

Status and phase: Completed; Phase 1

Conditions: Shigellosis

Treatments: Biological: Shigella flexneri 2a 2457T; Biological: Shigella sonnei 53G

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT04992520

CVIA 088

Details and patient eligibility

About

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).

Full description

This is a single-center controlled human infection model (CHIM) study designed to assess the cross-protective efficacy and markers of protection after challenge and heterologous rechallenge with Shigella strains of different serotypes in naïve healthy adult volunteers.

Enrollment: 46 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Healthy adults, male or female, aged 18 to 50 years (all inclusive) at the time of enrollment.
2. General good health, without clinically significant medical history, physical examination findings, or clinical laboratory abnormalities per judgment of Principal Investigator (PI).
3. Willingness to participate in the study after all aspects of the protocol have been explained and written informed consent obtained.
4. 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).
5. Availability for the study duration, including all planned follow-up visits.
6. Female participants must have a negative pregnancy test at screening and prior to each challenge.
7. 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).
8. Willingness to refrain from participation in a study of another investigational agent for 90 days following the last challenge dose.

Exclusion criteria

1. 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.
2. 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.
3. Recent receipt of another investigational product (within 30 days before enrollment).
4. Positive enzyme-linked immunosorbent assay (ELISA) and confirmatory tests for human immunodeficiency virus (HIV).
5. Positive hepatitis C (HCV) ELISA and confirmatory test (e.g., HCV ribonucleic acid (RNA)).
6. Positive hepatitis B virus surface antigen (HBsAg) by ELISA.
7. 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).
8. 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).
9. Immunoglobulin A (IgA) deficiency (serum IgA < 7 mg/dL or below the limit of detection of the assay).
10. Positive blood test for human leukocyte antigen (HLA)-B27.
11. Personal or family history of an inflammatory arthritis.
12. Currently pregnant or nursing.
13. Have household contacts who are < 2 years old or > 80 years old or infirm or immunocompromised.
14. 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.
15. Evidence of current alcohol or drug dependence, or history of dependence in the last 6 months.
16. Recent vaccination (including licensed vaccines) or receipt of an investigational product (within 30 days before challenge through 90 days following the last challenge dose). Annual influenza vaccine, an emergency authorized or licensed COVID-19 vaccine, or a TdaP or Travelers' diarrhea (TD) booster may be administered beyond 30 days after each challenge.
17. Treatment with immunoglobulins or blood products within 3 months of challenge.
18. Current or prior history of inflammatory bowel disease or irritable bowel syndrome or abnormal stool pattern (> 3/day or < 3/ week, or loose or liquid stools).
19. Chronic use of anti-diarrheal, anti-constipation, or antacid therapy; or use of these medications in the 7 days prior to challenge.
20. Use of proton pump inhibitors or H2 blockers (H2-receptor antagonists) within 48 hours prior to challenge.
21. Use of antibiotics within 7 days prior to challenge.
22. Known allergy to any 2 of the following antibiotics: ciprofloxacin, trimethoprim-sulfamethoxazole, or penicillin.
23. Symptoms of travelers' diarrhea associated with travel to countries where Shigella or other enteric infections are endemic (most of the developing world) within 3 years prior to challenge OR planned travel to endemic countries during the active study period.
24. History of shigellosis, Shigella vaccination or challenge, or a laboratory worker with known exposure to Shigella within the last 5 years.
25. Serum immunoglobulin G (IgG) titer > 2500 to either Shigella flexneri 2a or Shigella sonnei lipopolysaccharide.
26. Any other criteria which, in the investigator's opinion, would compromise the ability of the volunteer to participate in the study, the safety of the study, or the results of the study.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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46 participants in 6 patient groups

Group 1A: S. sonnei 53G

Experimental group

Description:

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

Treatment:

Biological: Shigella sonnei 53G

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

Experimental group

Description:

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.

Treatment:

Biological: Shigella flexneri 2a 2457T

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

Experimental group

Description:

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.

Treatment:

Biological: Shigella flexneri 2a 2457T

Group 2A: S. Flexneri 2a

Experimental group

Description:

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

Treatment:

Biological: Shigella flexneri 2a 2457T

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

Experimental group

Description:

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

Treatment:

Biological: Shigella sonnei 53G

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

Experimental group

Description:

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.

Treatment:

Biological: Shigella sonnei 53G