Controlled Human Infection Model Challenge/Rechallenge | NCT04992520

NCT04992520

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
United States Department of Defense	FED
Johns Hopkins University Center for Immunization Research (CIR)	UNKNOWN

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
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

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
Maximum Volume of Loose Stools in Any 24-hour Period	During the 8-day inpatient period after each challenge all stools were weighed and graded according to 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.	8 days after challenge administration (Days 1-8 and Days 90-97 for challenge 2)

Eligibility Module

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 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.

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).
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.
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.
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 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 immunoglobulin G (IgG) titer > 2500 to either Shigella flexneri 2a or Shigella sonnei lipopolysaccharide.
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.

Name	Affiliation	Role
Kawsar Talaat, MD	Johns Hopkins University	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Center for Immunization Research (CIR) at Johns Hopkins School of Public Health (JHSPH)		Baltimore	Maryland	21224	United States

Arm/Group Information

ID	Title	Description
FG000	Group 1A: S. Sonnei 53G	Naïve participants were challenged with 1500 colony forming units (CFU) of Shigella sonnei (S. sonnei) strain 53G.
FG001	Group 1B: S. Flexneri 2a (Naive)	At least 3 months after the challenge in Group 1A, newly recruited naïve participants were challenged with 1500 CFU of Shigella flexneri (S. flexneri) 2a strain 2457T.
FG002	Group 1B: S. Flexneri 2a (Veteran)	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.
FG003	Group 2A: S. Flexneri 2a	Naïve participants were challenged with 1500 CFU of S. flexneri 2a strain 2457T.
FG004	Group 2B: S. Sonnei 53G (Naive)	At least 3 months after the challenge in Group 2A, newly recruited naïve participants were challenged with 1500 CFU of S. sonnei 53G.
FG005	Group 2B: S. Sonnei 53G (Veteran)	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.

ID	Title	Description
BG000	Group 1A: S. Sonnei 53G	Naïve participants were challenged with 1500 CFU of S. sonnei strain 53G.
BG001	Group 1B: S. Flexneri 2a (Naive)	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.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
Primary	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.	Per-Protocol Population included participants who received the challenge dose and had no major protocol violations that were determined to potentially interfere with the clinical assessment.	Posted		Number	95% Confidence Interval	percentage of participants		8 days after challenge administration (Days 1-8 and Days 90-97 for challenge 2)

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Group 1A: S. Sonnei 53G	Naïve participants were challenged with 1500 CFU of S. sonnei strain 53G.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jan 16, 2023	Sep 4, 2024	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Oct 4, 2023	Sep 4, 2024	SAP_001.pdf

ID	Term
D004756	Enterobacteriaceae Infections
D016905	Gram-Negative Bacterial Infections
D001424	Bacterial Infections
D001423	Bacterial Infections and Mycoses