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Phase 2 Shigella Vaccine and Challenge

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04242264
Recruitment Status : Not yet recruiting
First Posted : January 27, 2020
Last Update Posted : July 25, 2022
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
This is a trial to evaluate the safety, reactogenicity, immunogenicity and efficacy of a 10^6 cfu dose of an oral live-attenuated S. sonnei vaccine candidate, WRSs2, in up to 120 healthy males and non-pregnant females aged 18-49, inclusive. This is a two-phase study, an outpatient WRSs2 vaccination phase and an inpatient S. sonnei 53G challenge phase. There are three groups in each phase. Outpatient WRSs2 phase: Group 1 will receive two doses of WRSs2 vaccine; Group 2 will receive one dose of the placebo and one dose of WRSs2 vaccine; Group 3 will receive two doses of the placebo. All three groups in an inpatient S. sonnei 53G challenge phase will receive one dose of S. sonnei 53G challenge. The study will be conducted in up to 3 Vaccine Treatment Evaluation Units (VTEU) sites. The study duration is approximately 24 months with subject participation duration approximately 8 months. The Primary Objective of this study is to estimate vaccine efficacy of 1 and 2 doses of WRSs2 in preventing shigellosis, following challenge with S. sonnei strain 53G.

Condition or disease Intervention/treatment Phase
Immunisation Shigella Infection Other: Placebo Biological: Shigella sonnei strain 53G Biological: WRSs2 Phase 2

Detailed Description:
This is a double-blind placebo-controlled trial to evaluate the safety, reactogenicity, immunogenicity and efficacy of a 10^6 cfu dose of an oral live-attenuated S. sonnei vaccine candidate, WRSs2, in up to 120 healthy males and non-pregnant females aged 18-49, inclusive. This is a two-phase study, an outpatient WRSs2 vaccination phase and an inpatient S. sonnei 53G challenge phase. There are three groups in each phase. Outpatient WRSs2 phase: Group 1 will receive two doses of WRSs2 vaccine; Group 2 will receive one dose of the placebo and one dose of WRSs2 vaccine; Group 3 will receive two doses of the placebo. All three groups in an inpatient S. sonnei 53G challenge phase will receive one dose of S. sonnei 53G challenge. The study will be conducted in up to 3 Vaccine Treatment Evaluation Units (VTEU) sites. The study duration is approximately 24 months with subject participation duration approximately 8 months. The Primary Objective of this study is to estimate vaccine efficacy of 1 and 2 doses of WRSs2 in preventing shigellosis, following challenge with S. sonnei strain 53G. The Secondary Objectives are to:1) Evaluate the safety of 1 and 2 doses of WRSs2; 2) Evaluate immune responses following vaccination (immunogenicity) with 1 and 2 doses of WRSs2 and after challenge with S. sonnei strain 53G by serum anti-LPS and anti-Invaplex IgG and IgA by ELISA; 3) Determine fecal shedding of S. sonnei after WRSs2 vaccination and 53G challenge by qualitative stool culture.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: A Double-Blind Placebo Controlled Phase 2 Trial to Evaluate the Safety, Reactogenicity and Immunogenicity of a Live-Attenuated Shigella Sonnei Vaccine, WRSs2 and Determine Its Efficacy in a Challenge Model of S. Sonnei 53G in Healthy Adults
Estimated Study Start Date : July 26, 2022
Estimated Primary Completion Date : January 5, 2023
Estimated Study Completion Date : January 5, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vaccines

Arm Intervention/treatment
Experimental: Group 1
Vaccine: 1 ml of saline containing 10^6 cfu of the WRSs2 vaccine in 30 ml of sterile normal saline administered orally on Day 1 and Day 29. N=8 Challenge: 1 ml of S. sonnei 53G challenge administered orally on Day 57. N=6
Biological: Shigella sonnei strain 53G
1.5 x 10^3 Colony Forming Units (cfu) Shigella sonnei 53G, a virulent strain of wildtype Shigella sonnei

Biological: WRSs2
10^6 Colony Forming Units (cfu) dose of an oral live-attenuated Shigella sonnei vaccine candidate derived from a virulent S. sonnei strain Moseley (WRSs2)-a live, attenuated vaccine that has been manufactured under cGMP conditions at the WRAIR PBF

Experimental: Group 2
Placebo+Vaccine: 30 ml of Placebo administered orally on Day 1 and 1 ml of saline containing 10^6 cfu of the WRSs2 vaccine in 30 ml of sterile normal saline administered orally on Day 29. N=8 Challenge: 1 ml of S. sonnei 53G challenge administered orally on Day 57. N=6
Other: Placebo
0.9% Sterile Normal Saline, USP

Biological: Shigella sonnei strain 53G
1.5 x 10^3 Colony Forming Units (cfu) Shigella sonnei 53G, a virulent strain of wildtype Shigella sonnei

Biological: WRSs2
10^6 Colony Forming Units (cfu) dose of an oral live-attenuated Shigella sonnei vaccine candidate derived from a virulent S. sonnei strain Moseley (WRSs2)-a live, attenuated vaccine that has been manufactured under cGMP conditions at the WRAIR PBF

Placebo Comparator: Group 3
Placebo: 30 ml of Placebo administered orally on Day 1 and Day 29. N=8 Challenge: 1 ml of S. sonnei 53G challenge administered orally on Day 57. N=6
Other: Placebo
0.9% Sterile Normal Saline, USP

Biological: Shigella sonnei strain 53G
1.5 x 10^3 Colony Forming Units (cfu) Shigella sonnei 53G, a virulent strain of wildtype Shigella sonnei




Primary Outcome Measures :
  1. Occurrence of shigellosis following challenge with Shigella sonnei strain 53G [ Time Frame: Day 57 through Day 63 ]

Secondary Outcome Measures :
  1. Duration of shedding 53G post-challenge [ Time Frame: Day 57 through Day 65 ]
  2. Duration of shedding Shigella sonnei by culture post-vaccination [ Time Frame: Day 1 through Day 57 ]
  3. Maximum Shigella sonnei LPS-specific and Invaplex-specific serum IgG and IgA titers [ Time Frame: Day 1 through Day 113 ]
  4. Number of subjects shedding 53G in their stool by culture [ Time Frame: Day 57 through Day 65 ]
  5. Number of subjects shedding vaccine strain in their stool by culture [ Time Frame: Day 1 through Day 36 ]
  6. Number of subjects with = / > 4-fold rise from pre-vaccination in Shigella sonnei LPS-specific and Invaplex-specific serum IgG and IgA [ Time Frame: Day 1 through Day 113 ]
  7. Occurrence of Serious Adverse Events (SAEs) [ Time Frame: Day 1 through Day 180 or resolution/stabilization ]
  8. Occurrence of solicited systemic Adverse Events (AEs) [ Time Frame: Day 1 through Day 36 ]
  9. Occurrence of vaccine-related unsolicited Adverse Events (AEs) [ Time Frame: Day 1 through Day 57 ]
  10. Peak fold-rise in S. sonnei LPS-specific and Invaplex-specific serum IgG and IgA titer from pre-challenge [ Time Frame: Day 1 through Day 113 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 49 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Provide informed consent prior to initiation of any study procedures.
  2. Are able to understand and comply with planned study procedures and be available for all study visits.
  3. Is 18-49 years of age inclusive and in sufficiently good health* to be safely enrolled in this study as determined by medical history, medication use, and abbreviated physical exam.

    *Good health is defined by the absence of any exclusionary medical conditions. If the subject has another current, ongoing medical condition, the condition cannot meet any of the following criteria: 1) first diagnosed within 3 months of enrollment; 2) is worsening in terms of clinical outcome in last 6 months; or 3) involves need for medication that may pose a risk to subject's safety or impede assessment of adverse events or immunogenicity if they participate in the study. Topical, nasal, and inhaled medications (with the exception of inhaled corticosteroids as outlined in the Subject Exclusion Criteria, herbals, vitamins, and supplements are permitted.

  4. Oral temperature is less than 100.4 degrees Fahrenheit.
  5. Pulse is 50 to 100 beats per minute (bpm), inclusive.
  6. Systolic blood pressure is 90 to 140 mmHg, inclusive.
  7. Diastolic blood pressure is 55 to 90 mmHg, inclusive.
  8. Females of childbearing potential** may enroll if subject has practiced adequate contraception*** = / > 30 days prior to enrollment and agrees to continue adequate contraception for the entire study.

    **Child-bearing potential is defined as not sterilized via tubal ligation, bilateral oophorectomy, salpingectomy, hysterectomy, or successful Essure(R) placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or <1 year of the last menses if menopausal.

    ***Adequate contraception includes; non-male sexual relationships, abstinence from sexual intercourse with a male partner, monogamous relationship with vasectomized partner who has been vasectomized for 180 days or more prior to the subject enrollment, barrier methods such as condoms or diaphragms with spermicide, effective intrauterine devices, NuvaRing(R), and licensed hormonal methods such as implants, injectables, or oral contraceptives ("the pill").

  9. Females of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to enrollment.
  10. Drug screen for opiates is negative.

Exclusion Criteria:

  1. Have any disease or medical condition that, in the opinion of the site principal investigator or appropriate sub-investigator, is a contraindication to study participation****.

    **** Including acute or chronic disease or medical condition that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this trial. These include:

    1. History of inflammatory bowel disease (IBD) (including ulcerative colitis, Crohn's disease, indeterminate colitis, or celiac disease).
    2. Irritable bowel syndrome (IBS) within the past 12 months or any active uncontrolled gastrointestinal disorders or diseases as assessed by the investigator. Including: symptoms or evidence of active gastritis or gastroesophageal reflux disease, gastric surgery or gastric acid hyper-secretory disorders (e.g., Zollinger-Ellison syndrome), gastrointestinal obstruction, ileus, gastric retention, bowel perforation, toxic colitis, persistent infectious gastroenteritis, persistent or chronic diarrhea of unknown etiology, Clostridium difficile infection.
    3. Known active neoplastic disease (Non-melanoma, treated, skin cancers are permitted), a history of any hematologic malignancy, or have used anticancer chemotherapy/radiation therapy (cytotoxic) within 3 years prior to study enrollment.
    4. Personal or family history of reactive arthritis.
    5. Reported history of HIV, Hepatitis B, or Hepatitis C
    6. History of immunodeficiency due to congenital or hereditary causes, underlying illness or treatment.
  2. Positive serology results for HLA-B27, HIV, HBsAg, or HCV antibodies.
  3. Have clinically significant abnormalities as determined by study investigator in other screening laboratory tests, as outlined in the protocol.
  4. Have participated in a previous Shigella challenge study or reports having received vaccination for Shigella previously.
  5. Have a previously laboratory confirmed case of disease caused by S. sonnei or serology positive (>1:2500) for anti S. sonnei LPS IgG ELISA titer at screening.
  6. Has a history of diarrhea in the 14 days prior to enrollment.
  7. Have fewer than 3 stools per week or more than 3 stools per day as the usual frequency.
  8. Recent history/current use of immunosuppressive/immunomodulating disease therapy.
  9. Known hypersensitivity to ciprofloxacin or trimethoprim-sulfamethoxazole; sodium bicarbonate; or any components of vaccine, placebo, or challenge material.
  10. Received or plan to receive a licensed live vaccine within 30 days prior to enrollment.
  11. Received or plan to receive a licensed, inactivated, vaccine (including the seasonal flu vaccine) within 14 days before enrollment.
  12. Have a history of severe reactions following previous immunization with any licensed or unlicensed vaccine.
  13. Received Ig or other blood products (with exception of Rho D Ig) within 90 days prior to enrollment.
  14. Have taken oral or parenteral (including intra-articular) corticosteroids of any dose, or high-dose inhaled corticosteroids***** within 30 days prior to enrollment.

    ***** High-dose defined per age as using inhaled high dose per reference chart Estimated Comparative Daily Dosages https://www.nhlbi.nih.gov/files/docs/guidelines/asthma_qrg.pdf

  15. Have taken antibiotics within 7 days prior to enrollment.
  16. Have taken prescription and/or OTC medication containing loperamide, acetaminophen, aspirin, ibuprofen, or other non-steroidal anti-inflammatory < / = 48 hours prior to enrollment.
  17. Have a history of alcohol or drug abuse within 1 year prior to enrollment.
  18. Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within 5 years prior to enrollment.
  19. Work or plan to work in either a health care setting, day care center, or as a food handler or have known daily contact with individuals with possible increased susceptibility****** to Shigella within 14 days after discharge from inpatient challenge.

    ****** Immunocompromised, elderly persons aged 70 years or more, diapered individuals, persons with disabilities, children < 2 years old, a woman known to be pregnant or nursing, or anyone with diminished immunity. Known daily contact includes contact at home, school, day-care, nursing home, or similar places.

  20. Are pregnant, breastfeeding or plan to become pregnant or breastfeed at any given time during the study.
  21. Have fever or an acute illness******* as determined by the site principal investigator or appropriate sub-investigator, within 72 hours prior to enrollment.

    ******* An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site principal investigator or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol

  22. Received an experimental agent (including vaccine, drug, biologic, device, blood product, or medication, other than from participation in this trial) within 30 days prior to the first study vaccination or expect to receive an investigational product during the study period which might affect safety or assessment of study endpoints.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04242264


Contacts
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Contact: Robert W. Frenck 15136367839 robert.frenck@cchmc.org

Locations
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United States, Ohio
Cincinnati Children's Hospital Medical Center - Infectious Diseases
Cincinnati, Ohio, United States, 45229-3039
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT04242264    
Other Study ID Numbers: 17-0112
HHSN272201300016I
First Posted: January 27, 2020    Key Record Dates
Last Update Posted: July 25, 2022
Last Verified: April 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Challenge
Double-blind
Efficacy
Healthy Adults
Immunogenicity
Live-attenuated Shigella sonnei Vaccine
Phase 2 Trial
Placebo-controlled
Protective efficacy
Reactogenicity
Safety
Shigella sonnei 53G Challenge
WRSs2
Additional relevant MeSH terms:
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Dysentery, Bacillary
Enterobacteriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Infections
Dysentery
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases