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Shigella Sonnei 53G Challenge

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ClinicalTrials.gov Identifier: NCT02816346
Recruitment Status : Completed
First Posted : June 28, 2016
Last Update Posted : April 11, 2018
Sponsor:
Collaborators:
United States Department of Defense
Children's Hospital Medical Center, Cincinnati
Information provided by (Responsible Party):
PATH

Brief Summary:
Development of an S. sonnei human challenge model using a newly manufactured lyophilized lot of S. sonnei strain 53G (Lot 1794) that can be used in the future as a challenge strain for all S. sonnei vaccine candidates. An adaptable dosing plan will be used to determine the dose of Shigella sonnei 53G that induces the primary outcome in approximately 60% of subjects.

Condition or disease Intervention/treatment Phase
Healthy Biological: Shigella sonnei 53G Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 46 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Dose-Finding Study of Lyophilized Shigella Sonnei 53G Challenge Strain
Study Start Date : September 12, 2016
Actual Primary Completion Date : December 31, 2017
Actual Study Completion Date : December 31, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: A
dose 500 cfu
Biological: Shigella sonnei 53G
Experimental: B
250 cfu or 1000 cfu (based on results of cohort A)
Biological: Shigella sonnei 53G
Experimental: C
TBD based on cohort A and B
Biological: Shigella sonnei 53G
Experimental: D
Based on results of previous cohorts
Biological: Shigella sonnei 53G



Primary Outcome Measures :
  1. Shigellosis [ Time Frame: abnormal clinical laboratory values within 11 days post challenge. ]
    Shedding of S. sonnei in the stool accompanied by moderate-severe diarrhea and/or dysentery along with fever or one or more severe intestinal symptoms.


Secondary Outcome Measures :
  1. Immunogenicity [ Time Frame: Up to study day 56 ]
    Systemic, mucosal, cell mediated immunogenicity. B memory cell assays. Fecal shedding of shigella.



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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. Male or non-pregnant female between 18 and 49 years of age (inclusive).
  2. General good health defined as (a) no significant medical illness, (b) no clinically significant physical examination findings and (c) no screening laboratory values significantly outside the normal limits of the testing laboratory within 45 days of challenge.
  3. Demonstrate comprehension of the protocol procedures and knowledge of study by passing a written examination (pass grade ≥70%) on day -1.
  4. Willing to sign an informed consent form (ICF).
  5. Willingness to participate for an inpatient stay lasting up to 11 days and an outpatient follow-up lasting 6 months from challenge.
  6. Willing to not smoke during the inpatient stay.
  7. Available for all planned follow-up visits.
  8. Negative serum pregnancy test at screening and negative urine pregnancy test on the day of admission to the inpatient phase for female subjects of childbearing potential. Females of childbearing potential must agree to use an effective method of birth control (birth control pills, injection hormonal contraceptive, implant hormonal contraceptive,

    hormonal patch, IUD, sterilization by hysterectomy or tubal ligation, spermicidal products and barrier methods such as cervical sponge, diaphragm, or condom) within two months of challenge and during the entire study. Abstinence is acceptable. A woman is eligible if she is monogamous with a vasectomized partner.

  9. Willing to not donate blood for up to 6 months after completion of the inpatient phase of the study.
  10. Willing to refrain from participation in another investigational vaccine or drug trial at least until after completion of the 6 month follow-up safety call.

Exclusion Criteria:

  1. Presence of a significant medical condition (e.g. psychiatric conditions, alcohol or illicit drug abuse/dependency, or gastrointestinal disease, such as peptic ulcer, symptoms or evidence of active gastritis or gastroesophageal reflux disease, inflammatory bowel disease), or other laboratory abnormalities which in the opinion of the investigator precludes participation in the study.
  2. Immunosuppressive illness or IgA deficiency
  3. Positive serology results for HIV, HBsAg, HCV, or RPR (syphilis) antibodies.
  4. Evidence of inflammatory arthritis on exam and/or HLA-B27 positive.
  5. Family history of inflammatory arthritis.
  6. Significant abnormalities in screening lab hematology or serum chemistry, as determined by PI.
  7. Allergy to fluoroquinolones or trimethoprim-sulfamethoxazole
  8. Fewer than 3 stools per week or more than 3 stools per day as the usual frequency.
  9. History of diarrhea in the 2 weeks prior to planned inpatient phase
  10. Use of antibiotics during the 7 days before receiving the challenge inoculum dosing
  11. Use of prescription and/or OTC medications that contain Imodium, acetaminophen, aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs, during the 48 hours prior to investigational product administration
  12. Travel within two years prior to dosing to countries where Shigella infection is endemic.
  13. Use of any medication known to affect the immune function [e.g., oral steroids, parenteral steroids, or high-dose inhaled steroids (>800 μg/day of beclomethasone dipropionate or equivalent and others): nasal and topical steroids are allowed] within 30 days preceding receipt of the challenge inoculum or planned use during the active study period.
  14. Serologic evidence of Shigella sonnei (titer > 1:2500)
  15. A positive urine test for opiates.
  16. A chronic disease (such as hypertension, hyperlipidemia or anxiety/depression) for which doses of prescription medications are not stable for at least the past 3 months.
  17. Scheduled and/or long-term use of oral steroids, parenteral steroids, or high-dose inhaled steroids (>800 μg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months (Nasal, intra-articular, and topical steroids are allowed)
  18. Have immunocompromised household contacts.
  19. A clinically significant abnormality on physical examination, including a systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg, or a resting pulse >100 beats/min or <55 beats/min (<50 beats/min for conditioned athletes).
  20. Pregnant, nursing, or plan to become pregnant within 6 months of receipt of the study product.
  21. In the 4 weeks following challenge, subject will be living with or having daily contact with elderly persons aged 70 years or more, diapered individuals, persons with disabilities, children <2 years old, or a woman known to be pregnant or nursing, or anyone with diminished immunity. This includes contact at home, school, day-care, nursing homes, or similar places.
  22. Work in a health care setting, day care center, or as a food handler in the 4 weeks following the challenge with S. sonnei.
  23. Use of any investigational drug or any investigational vaccine within 60 days preceding challenge, or planned use during the 6 months after receipt of the study agent.
  24. Have received a licensed, live vaccine within 28 days or a licensed inactivated vaccine within 14 days of receiving the challenge inoculum.
  25. Inability to comply with inpatient rules and regulations.
  26. Has any other condition that, in the opinion of the Investigator, would jeopardize the safety or rights of a participant or would render the subject unable to comply with the protocol.
  27. Received blood or blood products within the past six months.

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): NCT02816346


Locations
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United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
PATH
United States Department of Defense
Children's Hospital Medical Center, Cincinnati
Investigators
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Principal Investigator: Robert Frenck, MD Children's Hospital Medical Center, Cincinnati

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Responsible Party: PATH
ClinicalTrials.gov Identifier: NCT02816346     History of Changes
Other Study ID Numbers: VAC-048
First Posted: June 28, 2016    Key Record Dates
Last Update Posted: April 11, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by PATH:
shigella

Additional relevant MeSH terms:
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Dysentery, Bacillary
Enterobacteriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Dysentery
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases