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Controlled Human Infection Model Challenge/Rechallenge

Primary Purpose

Shigellosis

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
S. sonnei 53G
S. flexneri 2a 2457T
Sponsored by
PATH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Shigellosis

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts 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 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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Group 1A: S. sonnei 53G

Group 1B: S. flexneri 2a 2457T

Group 2A: S. flexneri 2a 2457T (1500 cfu)

Group 2B: S. sonnei 53G

Arm Description

30 naïve participants will be challenged with 1500 colony forming units (cfu) of S. sonnei 53G Mode of Administration: After a 90 minute fast subjects will drink the 120 mL of sodium bicarbonate (to neutralize gastric acidity) and then drink the challenge suspension within 2 minutes.

At least 3 months after challenging Group 1A, 20 of those volunteers, along with 10 newly recruited naïve participants, will be challenged with 1500 cfu of S. flexneri 2a Mode of Administration: After a 90 minute fast subjects will drink the 120 mL of sodium bicarbonate (to neutralize gastric acidity) and then drink the challenge suspension within 2 minutes.

30 naïve participants will be challenged with 1500 colony forming units (cfu) of S. flexneri 2a Mode of Administration: After a 90 minute fast subjects will drink the 120 mL of sodium bicarbonate (to neutralize gastric acidity) and then drink the challenge suspension within 2 minutes.

At least 3 months after challenging Group 2A, 20 of those volunteers, along with 10 newly recruited naïve participants, will be challenged with 1500 cfu of S. sonnei 53G Mode of Administration: After a 90 minute fast subjects will drink the 120 mL of sodium bicarbonate (to neutralize gastric acidity) and then drink the challenge suspension within 2 minutes.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
July 28, 2021
Last Updated
March 22, 2023
Sponsor
PATH
Collaborators
United States Department of Defense, Johns Hopkins University Center for Immunization Research (CIR)
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1. Study Identification

Unique Protocol Identification Number
NCT04992520
Brief Title
Controlled Human Infection Model Challenge/Rechallenge
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 26, 2022 (Actual)
Primary Completion Date
September 15, 2023 (Anticipated)
Study Completion Date
September 15, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PATH
Collaborators
United States Department of Defense, Johns Hopkins University Center for Immunization Research (CIR)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Shigellosis

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
46 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1A: S. sonnei 53G
Arm Type
Experimental
Arm Description
30 naïve participants will be challenged with 1500 colony forming units (cfu) of S. sonnei 53G Mode of Administration: After a 90 minute fast subjects will drink the 120 mL of sodium bicarbonate (to neutralize gastric acidity) and then drink the challenge suspension within 2 minutes.
Arm Title
Group 1B: S. flexneri 2a 2457T
Arm Type
Experimental
Arm Description
At least 3 months after challenging Group 1A, 20 of those volunteers, along with 10 newly recruited naïve participants, will be challenged with 1500 cfu of S. flexneri 2a Mode of Administration: After a 90 minute fast subjects will drink the 120 mL of sodium bicarbonate (to neutralize gastric acidity) and then drink the challenge suspension within 2 minutes.
Arm Title
Group 2A: S. flexneri 2a 2457T (1500 cfu)
Arm Type
Experimental
Arm Description
30 naïve participants will be challenged with 1500 colony forming units (cfu) of S. flexneri 2a Mode of Administration: After a 90 minute fast subjects will drink the 120 mL of sodium bicarbonate (to neutralize gastric acidity) and then drink the challenge suspension within 2 minutes.
Arm Title
Group 2B: S. sonnei 53G
Arm Type
Experimental
Arm Description
At least 3 months after challenging Group 2A, 20 of those volunteers, along with 10 newly recruited naïve participants, will be challenged with 1500 cfu of S. sonnei 53G Mode of Administration: After a 90 minute fast subjects will drink the 120 mL of sodium bicarbonate (to neutralize gastric acidity) and then drink the challenge suspension within 2 minutes.
Intervention Type
Biological
Intervention Name(s)
S. sonnei 53G
Intervention Description
Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast
Intervention Type
Biological
Intervention Name(s)
S. flexneri 2a 2457T
Intervention Description
Shigella flexneri strain 2457T (Lot 1617) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast.
Primary Outcome Measure Information:
Title
Number of Participants With Shigellosis
Description
-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
Time Frame
11 days after challenge administration

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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 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. Exclusion Criteria: 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). IgA deficiency (serum IgA < 7 mg/dL or below the limit of detection of the assay). Positive blood test for HLA-B27. Personal or family history of an inflammatory arthritis. Currently pregnant or nursing. Evidence of current alcohol or drug dependence, or history of dependence in the last 6 months. 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. Treatment with immunoglobulins or blood products within 3 months of challenge. 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). Chronic use of anti-diarrheal, anti-constipation, or antacid therapy; or use of these medications in the 7 days prior to challenge. Use of proton pump inhibitors or H2 blockers (H2-receptor antagonists) within 48 hours prior to challenge. Use of antibiotics within 7 days prior to challenge. Known allergy to any 2 of the following antibiotics: ciprofloxacin, trimethoprim-sulfamethoxazole, or penicillin. 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. History of shigellosis, Shigella vaccination or challenge, or a laboratory worker with known exposure to Shigella within the last 5 years. Serum IgG titer > 2500 to either Shigella flexneri 2a or Shigella sonnei LPS. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kawsar Talaat, MD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Center for Immunization Research (CIR) at Johns Hopkins School of Public Health (JHSPH)
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States

12. IPD Sharing Statement

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Controlled Human Infection Model Challenge/Rechallenge

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