Controlled Human Infection Model Challenge/Rechallenge

Shigellosis Clinical Trial

Official title:

Controlled Human Infection Model Challenge/Rechallenge: Shigella Flexneri 2a and S. Sonnei Cross-protective Antigens Discovery in Healthy Adults in the United States

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04992520
• Other study ID #: CVIA 088
• Status: Completed
• Phase: Phase 1
• Start date: April 26, 2022
• Est. completion date: August 29, 2023

Study information

• Verified date: March 2023
• Source: PATH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study will compare the shigellosis rate in subjects previously challenged with a heterologous Shigella serotype to the attack rate in naïve subjects.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: August 29, 2023
• Est. primary completion date: August 29, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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 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. IgA deficiency (serum IgA < 7 mg/dL or below the limit of detection of the assay).

10. Positive blood test for HLA-B27.

11. Personal or family history of an inflammatory arthritis.

12. Currently pregnant or nursing.

13. Evidence of current alcohol or drug dependence, or history of dependence in the last 6 months.

14. 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 TD booster may be administered beyond 30 days after each challenge.

15. Treatment with immunoglobulins or blood products within 3 months of challenge.

16. 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).

17. Chronic use of anti-diarrheal, anti-constipation, or antacid therapy; or use of these medications in the 7 days prior to challenge.

18. Use of proton pump inhibitors or H2 blockers (H2-receptor antagonists) within 48 hours prior to challenge.

19. Use of antibiotics within 7 days prior to challenge.

20. Known allergy to any 2 of the following antibiotics: ciprofloxacin, trimethoprim-sulfamethoxazole, or penicillin.

21. Symptoms of travelers' diarrhea (TD) 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.

22. History of shigellosis, Shigella vaccination or challenge, or a laboratory worker with known exposure to Shigella within the last 5 years.

23. Serum IgG titer > 2500 to either Shigella flexneri 2a or Shigella sonnei LPS.

24. 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.

Related Conditions & MeSH terms

• Dysentery, Bacillary
• Shigellosis

Intervention

Biological:
• S. sonnei 53G
Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast
• S. flexneri 2a 2457T
Shigella flexneri strain 2457T (Lot 1617) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast.

Locations

Country	Name	City	State
United States	Center for Immunization Research (CIR) at Johns Hopkins School of Public Health (JHSPH)	Baltimore	Maryland

Sponsors (3)

Lead Sponsor	Collaborator
PATH	Johns Hopkins University Center for Immunization Research (CIR), United States Department of Defense

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Shigellosis	-Severe diarrhea (=6 loose [grade 3-5] stools within 24h or >800 - 999 grams loose [grade 3-5] stools within any 24-hour window); OR; -Moderate diarrhea (4 to 5 loose [grade 3-5] stools within 24h or 401-800 grams loose [grade 3-5] stools within any 24-hour window) with fever (Oral temperature of =101.2°F) OR with one or more 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	11 days after challenge administration