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ShigellosisPhase 1NCT04992520

Controlled Human Infection Model Challenge/Rechallenge

A Phase 1 study testing Shigella sonnei 53G and Shigella flexneri 2a 2457T in people with Shigellosis, run by PATH at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for
Shigellosis
What is being tested?
Shigella sonnei 53G and Shigella flexneri 2a 2457T
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
1 siteUnited States
Study dates
26 Apr 2022to 29 Aug 2023
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

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

    Baltimore, Maryland, 21224

Other trials in United States

About this study

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

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).

Read the 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.

Conditions
Shigellosis
Being tested
Shigella sonnei 53G, Shigella flexneri 2a 2457T
Medical subject headings
Dysentery, Bacillary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Shigella sonnei 53GBiological

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

  • Shigella flexneri 2a 2457TBiological

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

Study groups in NCT04992520
Study groupRoleWhat they receive
Group 1A: S. sonnei 53GExperimentalNaïve participants were challenged with 1500 colony forming units (CFU) of S. sonnei strain 53G.
Receives: Biological: Shigella sonnei 53G
Group 1B: S. flexneri 2a 2457T (Naive)ExperimentalAt least 3 months after the challenge in Group 1A, newly recruited naïve participants were challenged with 1500 CFU of S. flexneri 2a strain 2457T.
Receives: Biological: Shigella flexneri 2a 2457T
Group 1B: S. Flexneri 2a (Veteran)ExperimentalAt 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.
Receives: Biological: Shigella flexneri 2a 2457T
Group 2A: S. Flexneri 2aExperimentalNaïve participants were challenged with 1500 CFU of S. flexneri 2a strain 2457T.
Receives: Biological: Shigella flexneri 2a 2457T
Group 2B: S. Sonnei 53G (Naive)ExperimentalAt least 3 months after the challenge in Group 2A, newly recruited naïve participants were challenged with 1500 CFU of S. sonnei 53G.
Receives: Biological: Shigella sonnei 53G
Group 2B: S. Sonnei 53G (Veteran)ExperimentalAt least 3 months after challenge with S. flexneri 2a in Group 2A, participants received a 2nd challenge with 1500 CFU of S. sonnei 53G.
Receives: Biological: Shigella sonnei 53G

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (11)

  1. 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.

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

  2. Percentage of Participants With Severe Diarrhea

    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.

    Severe diarrhea was defined as ≥ 6 loose (Grade 3-5) stools within 24 hours or > 800 grams of loose (Grade 3-5) stools within any 24-hour window.

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

  3. Percentage of Participants With Diarrhea of Any Severity

    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.

    Participants met the criteria for diarrhea if they had ≥ 2 loose (Grade 3-5) stools weighing ≥ 200 grams within any 48-hour window or any loose stools weighing ≥ 300 grams.

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

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

    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.

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

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

    During the 8-day inpatient period after each challenge, nausea, vomiting, anorexia, and abdominal pain/cramps were monitored and graded (except for vomiting) according to the following:

    Mild: Discomfort noted, but no disruption of normal daily activities; slightly bothersome; relieved with or without symptomatic treatment.

    Moderate: Discomfort sufficient to reduce or affect normal daily activity to some degree; bothersome; interferes with activities, only partially relieved with symptomatic treatment.

    Severe: Discomfort sufficient to reduce or affect normal daily activity considerably; prevents regular activities; not relieved with symptomatic treatment.

    Vomiting was graded according the the following:

    Mild: One episode within a 24-hour period Moderate: Two episodes within a 24-hour period Severe: Three or more episodes within a 24-hour period.

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

  6. Percentage of Participants With Dysentery

    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.

    Dysentery was defined as ≥ 2 loose stools (Grade 3-5) 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 included nausea, abdominal cramps/pain, myalgia, arthralgia, and malaise.

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

  7. Time to Onset of Diarrhea

    Measured: From challenge administration to the end of the 8-day inpatient period (Days 1-8 and Days 90-97 for challenge 2)

  8. Number of Participants With More Severe Diarrhea

    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.

    More severe diarrhea was defined as ≥ 10 loose (Grade 3-5) stools within 24 hours or ≥ 1000 grams loose stools within any 24-hour window.

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

  9. Number of Participants With Fever After Challenge

    Fever: measured oral temperature ≥ 38°C confirmed within about 20 minutes.

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

  10. Shigella Clinical Severity Score

    The Shigella clinical severity score is a composite, ordinal disease score that consists of three parameters: self-reported symptoms (arthralgia, nausea, myalgia, headache, anorexia, and abdominal cramps and pain), clinical signs (blood in stool, fever, and vomiting) and stool output (maximum loose stool output / 24 hours). Each parameter is scored based off maximum severity clinical signs, self-reported symptoms and stool output experienced over over the 8-day period.

    The Shigella clinical severity score ranges from 0 to 9, where 0 = no or mild symptoms only and 9 = severe symptoms.

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

  11. Number of Colony Forming Units (CFUs) of the Challenge Strain Per Gram of Stool

    Analysis of stool samples to quantify challenge strains in the stool are not yet complete. Data will be reported once the assays have been completed.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Aug 2021
  2. Study start26 Apr 2022
  3. Primary completion29 Aug 2023
  4. Study completion29 Aug 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Non-randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04992520
Sponsor's protocol ID
CVIA 088
Status last verified
Dec 2024
First submitted
28 Jul 2021
Last updated
31 Jan 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Shigella sonnei 53G and Shigella flexneri 2a 2457T in people with Shigellosis, run by PATH at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Shigellosis Following Shigella Challenge (time frame: 8 days after challenge administration (Days 1-8 and Days 90-97 for challenge 2)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04992520.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2025.

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