NCT01509846

Brief Summary

This is a research study about an experimental (investigational) oral inactivated whole cell Shigella flexneri 2a killed vaccine (Sf2aWC). Sf2aWC is a killed vaccine that is being made to prevent disease from Shigella., which causes bloody, watery diarrhea. Infants and children living in developing countries experience the greatest consequences of this disease. The purpose of this study is to find a dose of the vaccine that is safe, tolerable, and develops an immune response. About 82 healthy adults, ages 18-45, will participate in this study. This study will require volunteers to stay in the research facility for several nights for the first dose. Participants in Cohorts 2, 3, and 4 will not be required to stay overnight for the second and third doses. Participants will be assigned to receive 1 of 4 vaccine doses by mouth. Study procedures include: stool samples, blood samples and documenting side effects. Participants will be involved in study related procedures for about 8 months.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
82

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Mar 2011

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2011

Completed
10 months until next milestone

First Submitted

Initial submission to the registry

January 5, 2012

Completed
8 days until next milestone

First Posted

Study publicly available on registry

January 13, 2012

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2012

Completed
8.7 years until next milestone

Results Posted

Study results publicly available

August 11, 2021

Completed
Last Updated

August 11, 2021

Status Verified

July 1, 2021

Enrollment Period

1.8 years

First QC Date

January 5, 2012

Results QC Date

July 31, 2018

Last Update Submit

August 10, 2021

Conditions

Shigellosis

Keywords

Shigellavaccineshigellosisdysenterywhole cell

Outcome Measures

Primary Outcomes (2)

  • Maximum Reactogenicity Per Subject and Treatment Group

    Local and systemic reactogenicity was assessed post-vaccination using targeted physical examinations, vital signs and clinical laboratory tests, and diary cards (completed following discharge daily through Day 7). Reactogenicity included: nausea, vomiting, fever, abdominal pain, abdominal cramping, bloating, malaise, headache, decreased appetite, generalized myalgias, chills, light-headedness, constipation, excessive flatulence, reactive arthritis, dysentery, loose stool, diarrhea, hypovolemia, joint pain, defecation urgency, and oral temperature.

    7 days after each vaccination (Day 0, Day 35, Day 63)

  • Frequency of Unsolicited Adverse Events With a Reasonable Possibility That the Study Product Caused the Event

    6 months after final vaccination (Day 168 or Day 224)

Secondary Outcomes (24)

  • Number and Percentage of Subjects in Cohort 3 With Positive Immunologic Response in Serum Lipopolysaccharide (LPS) Immunoglobulin A (IgA) Response From Baseline

    35 days

  • Number and Percentage of Subjects in Cohort 4 With Positive Immunologic Response in Serum Lipopolysaccharide (LPS) Immunoglobulin A (IgA) Response From Baseline

    63 days

  • Geometric Mean Titer (GMT) of Serum Lipopolysaccharide (LPS) Immunoglobulin A (IgA) Response in Cohort 3

    35 days

  • Geometric Mean Titer (GMT) of Serum Lipopolysaccharide (LPS) Immunoglobulin A (IgA) Response in Cohort 4

    63 days

  • Number and Percentage of Subjects in Cohort 3 With Positive Immunologic Response in Serum Lipopolysaccharide (LPS) Immunoglobulin G (IgG) Response From Baseline

    16 weeks

  • +19 more secondary outcomes

Study Arms (5)

Cohort 1

EXPERIMENTAL

Received one oral dose of 2.6±0.8 x 10\^8 vp/mL Shigella flexneri 2a whole cell killed vaccine (Sf2aWC)

Biological: Vaccine: 2.6±0.8 x 10^8 vp/mL, 1 dose

Cohort 2

EXPERIMENTAL

Received three oral doses of 2.6±0.8 x 10\^9 vp/mL Shigella flexneri 2a whole cell killed vaccine (Sf2aWC)

Biological: Vaccine: 2.6±0.8 x 10^9 vp/mL, 3 doses

Cohort 3

EXPERIMENTAL

Received three oral doses of 2.6±0.8 x 10\^10 vp/mL Shigella flexneri 2a whole cell killed vaccine (Sf2aWC)

Biological: Vaccine: 2.6±0.8 x 10^10 vp/mL, 3 doses

Cohort 4

EXPERIMENTAL

Received three oral doses of 2.6±0.8 x 10\^11 vp/mL Shigella flexneri 2a whole cell killed vaccine (Sf2aWC)

Biological: Vaccine: 2.6±0.8 x 10^11 vp/mL, 3 doses

Placebo

PLACEBO COMPARATOR

Received oral dose of placebo concurrent with Cohort 1 (one dose), 2, 3, or 4 (3 doses).

Biological: Placebo: 1-3 doses

Interventions

Vaccine: 2.6±0.8 x 10^8 vp/mL, 1 doseBIOLOGICAL

Shigella flexneri 2a whole cell killed vaccine (Sf2aWC): 2.6±0.8 x 10\^8 vp/mL administered on Day 0

Cohort 1
Vaccine: 2.6±0.8 x 10^9 vp/mL, 3 dosesBIOLOGICAL

Shigella flexneri 2a whole cell killed vaccine (Sf2aWC): 2.6±0.8 x 10\^9 vp/mL administered on Days 0, 28, and 56

Cohort 2
Vaccine: 2.6±0.8 x 10^10 vp/mL, 3 dosesBIOLOGICAL

Shigella flexneri 2a whole cell killed vaccine (Sf2aWC): 2.6±0.8 x 10\^10 vp/mL administered on Days 0, 28, and 56

Cohort 3
Vaccine: 2.6±0.8 x 10^11 vp/mL, 3 dosesBIOLOGICAL

Shigella flexneri 2a whole cell killed vaccine (Sf2aWC): 2.6±0.8 x 10\^11 vp/mL administered on Days 0, 28, and 56

Cohort 4
Placebo: 1-3 dosesBIOLOGICAL

Placebo administered on Day 0 (if 1 dose) or Day 0, 28, and 56 (3 doses)

Placebo

Eligibility Criteria

Age18 Years - 45 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Healthy adults, male or female, age 18 to 45 years (inclusive) at the time of enrollment.
  • Completion and review of comprehension test (achieved \>70% accuracy).
  • Signed informed consent form.
  • Available for the required follow-up period and scheduled clinic visits.
  • Negative urine pregnancy test before each vaccination for female subjects of childbearing potential. Females of childbearing potential must agree to use an efficacious hormonal or barrier method of birth control during the study. Abstinence is also acceptable.

You may not qualify if:

  • 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. These conditions might include stable asthma, hypertension or depression controlled with medication.
  • Clinically significant abnormalities on physical examination.
  • Clinically significant abnormalities in screening hematology, serum chemistry, or urinalysis as determined by PI or PI in consultation with Medical Monitor.
  • History of febrile illness within 48 hours prior to vaccination.
  • BMI \<19 or \>34.
  • Positive blood test for HBsAG, hepatitis C virus (HCV), HIV-1, Human leukocyte antigen (HLA)-B27.
  • Women currently nursing.
  • History of reactive arthritis.
  • Evidence of current excessive alcohol consumption
  • Evidence of current drug use or drug dependence.
  • Regular use of anti-diarrheal, anti-constipation, or antacid therapy (excluding use associated with spicy meals).
  • Abnormal stool pattern (fewer than 3 stools per week or more than 3 stools per day) on a regular basis; loose or liquid stools on other than an occasional basis.
  • Personal or family history of an inflammatory arthritis.
  • History of allergy to soy products.
  • History of microbiologically confirmed Shigella infection within 3 years.
  • +9 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

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

Baltimore, Maryland, 21224, United States

Location

Johns Hopkins University CIR Isolation Unit

Baltimore, Maryland, 21224, United States

Location

Related Publications (1)

  • Chakraborty S, Harro C, DeNearing B, Bream J, Bauers N, Dally L, Flores J, Van de Verg L, Sack DA, Walker R. Evaluation of the Safety, Tolerability, and Immunogenicity of an Oral, Inactivated Whole-Cell Shigella flexneri 2a Vaccine in Healthy Adult Subjects. Clin Vaccine Immunol. 2016 Apr 4;23(4):315-25. doi: 10.1128/CVI.00608-15. Print 2016 Apr.

    PMID: 26865592RESULT

MeSH Terms

Conditions

Dysentery, BacillaryDysentery

Condition Hierarchy (Ancestors)

Enterobacteriaceae InfectionsGram-Negative Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfectionsGastroenteritisGastrointestinal DiseasesDigestive System DiseasesIntestinal Diseases

Results Point of Contact

Title
Jorge Flores
Organization
PATH
jeflores@path.org
(202) 822-0033

Study Officials

  • Clayton D Harro, MD, ScM

    Johns Hopkins Bloomberg School of Public Health

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 5, 2012

First Posted

January 13, 2012

Study Start

March 1, 2011

Primary Completion

December 1, 2012

Study Completion

December 1, 2012

Last Updated

August 11, 2021

Results First Posted

August 11, 2021

Record last verified: 2021-07

Locations

US(2)