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Prevention of GBS Colonization Via Immunity

Primary Purpose

Beta Haemolytic Streptococcal Infection

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
GBS III-TT
Tetanus and diptheria toxoids vaccine
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Beta Haemolytic Streptococcal Infection focused on measuring Group B Streptococcus, women, vaccine

Eligibility Criteria

18 Years - 40 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria: Participated in and completed the group B Streptococcus (GBS) Screening Protocol Non-pregnant women Aged 18-40 years at time of the screening protocol Currently sexually active at time of enrollment (sex with a male at least once in the last 4 months) Current use of effective birth control methods and stated intention to use the method for at least the next 30 days Provision of written informed consent Intention to stay in the geographical area for the next 18 months Access to telephone Exclusion Criteria: Group B Streptococcus (GBS) positive by culture (vaginal and/or rectal), or culture positive for streptococcal strains that cross-react with GBS typing sera (vaginal and/or rectal). Pregnancy (all women will receive a urine pregnancy prior to vaccination). Any condition which in the opinion of the investigator would pose a health risk to the subject or interfere with the evaluation of the vaccine. Serious underlying disease, which is known at the time of vaccination (including: immunodeficiency, active or chronic hepatitis, immunosuppressive conditions which require systemic steroid therapy, or treatment for a malignancy during the past year). Receipt of any vaccine, blood product, or experimental medicine within the past 30 days with the exception of a licensed inactivated influenza vaccine. Plans to receive any vaccine, blood product, or experimental medicine in the next 30 days with the exception of a licensed inactivated influenza vaccine. Use of any antimicrobial agent(s) (vaginal or systemic) for treatment of any condition within 7 days prior to study enrollment (including: Monistat, Gyne-Lotrimin, et cetera ) History of hypersensitivity to tetanus toxoid vaccine. Tetanus toxoid immunization within the previous 12 months. Previous participation in a study in which participants received tetanus toxoid vaccine or vaccine against Group B Streptococcus. Spontaneous or surgical menopause. Nursing mother. Hypersensitivity to thimerosal.

Sites / Locations

  • Medical College of Georgia
  • Magee-Womens Hospital
  • Planned Parenthood of Houston and Southeast Texas, Inc.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

GBS III-TT

Td

Arm Description

A single dose of GBS III-TT vaccine administered intramuscularly (IM) containing 50 mcg of GBS III capsular polysaccharide and 32 mcg of tetanus toxoid.

The control group will receive a single dose of Tetanus and Diphtheria Toxoids (Td) vaccine.

Outcomes

Primary Outcome Measures

The Time to First Vaginal Swab That is Type III GBS Culture Positive, With All Previous Cultures Negative for Type III GBS, Not Just the Immediately Preceding Culture.
Time to first acquisition of vaginal type III GBS was calculated as time from vaccination to the mid-point of the interval of ascertainment, censored by either the end of the follow-up period, or the first of 2 or more consecutive missed visits. Vaginal type III GBS status at missed visits prior to censoring was imputed from the subsequent visit.

Secondary Outcome Measures

Geometric Mean Concentration (GMC) of Serum Immunoglobulin G (IgG) Antibody Levels to Type III GBS Post-Vaccination.
The GMC was calculated from IgG antibody to type III GBS assay results on serum specimens obtained at clinic visits during the 18 month post-vaccination follow-up period. Results at missed visits prior to loss to follow-up/final visit were not imputed.
Number of Participants With Any Solicited Local and Systemic Symptoms.
Participants maintained a diary card to report the occurrence of solicited local and systemic symptoms for 7 days after vaccination. Participants are counted if they indicated experiencing the symptom at any severity during the reporting period.
Mean Fold-Rise in Serum IgG Antibody Levels to Type III GBS Post-Vaccination
Fold-rises compare the IgG antibody level at post-vaccination to that obtained just prior to vaccination, for each visit during the 18-month follow-up period. Assay results at missed visits prior to loss to follow-up/final visit were not imputed.
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 1 Post-Vaccination
Blood samples were collected from participants prior to vaccination and at 1 month post vaccination, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The lower detection limit for the assay was 0.08 micrograms/milliliter (µg/mL), and antibody levels below this limit were recorded as 0.04 µg/mL by the laboratory. Fold rises compare IgG antibody levels at the post-vaccination visit to that obtained just prior to vaccination. Participants are considered a responder if the antibody increase was four-fold or greater.
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 2 Post-Vaccination
Blood samples were collected from participants prior to vaccination and at 2 months post vaccination, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The lower detection limit for the assay was 0.08 micrograms/milliliter (µg/mL), and antibody levels below this limit were recorded as 0.04 µg/mL by the laboratory. Fold rises compare IgG antibody levels at the post-vaccination visit to that obtained just prior to vaccination. Participants are considered a responder if the antibody increase was four-fold or greater.
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 4 Post-Vaccination
Blood samples were collected from participants prior to vaccination and at 4 months post vaccination, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The lower detection limit for the assay was 0.08 micrograms/milliliter (µg/mL), and antibody levels below this limit were recorded as 0.04 µg/mL by the laboratory. Fold rises compare IgG antibody levels at the post-vaccination visit to that obtained just prior to vaccination. Participants are considered a responder if the antibody increase was four-fold or greater.
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 6 Post-Vaccination
Blood samples were collected from participants prior to vaccination and at 6 months post vaccination, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The lower detection limit for the assay was 0.08 micrograms/milliliter (µg/mL), and antibody levels below this limit were recorded as 0.04 µg/mL by the laboratory. Fold rises compare IgG antibody levels at the post-vaccination visit to that obtained just prior to vaccination. Participants are considered a responder if the antibody increase was four-fold or greater.
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 8 Post-Vaccination
Blood samples were collected from participants prior to vaccination and at 8 month post vaccination, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The lower detection limit for the assay was 0.08 micrograms/milliliter (µg/mL), and antibody levels below this limit were recorded as 0.04 µg/mL by the laboratory. Fold rises compare IgG antibody levels at the post-vaccination visit to that obtained just prior to vaccination. Participants are considered a responder if the antibody increase was four-fold or greater.
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 10 Post-Vaccination
Blood samples were collected from participants prior to vaccination and at 10 months post vaccination, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The lower detection limit for the assay was 0.08 micrograms/milliliter (µg/mL), and antibody levels below this limit were recorded as 0.04 µg/mL by the laboratory. Fold rises compare IgG antibody levels at the post-vaccination visit to that obtained just prior to vaccination. Participants are considered a responder if the antibody increase was four-fold or greater.
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 12 Post-Vaccination
Blood samples were collected from participants prior to vaccination and at 12 months post vaccination, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The lower detection limit for the assay was 0.08 micrograms/milliliter (µg/mL), and antibody levels below this limit were recorded as 0.04 µg/mL by the laboratory. Fold rises compare IgG antibody levels at the post-vaccination visit to that obtained just prior to vaccination. Participants are considered a responder if the antibody increase was four-fold or greater.
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 14 Post-Vaccination
Blood samples were collected from participants prior to vaccination and at 14 months post vaccination, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The lower detection limit for the assay was 0.08 micrograms/milliliter (µg/mL), and antibody levels below this limit were recorded as 0.04 µg/mL by the laboratory. Fold rises compare IgG antibody levels at the post-vaccination visit to that obtained just prior to vaccination. Participants are considered a responder if the antibody increase was four-fold or greater.
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 16 Post-Vaccination
Blood samples were collected from participants prior to vaccination and at 16 months post vaccination, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The lower detection limit for the assay was 0.08 micrograms/milliliter (µg/mL), and antibody levels below this limit were recorded as 0.04 µg/mL by the laboratory. Fold rises compare IgG antibody levels at the post-vaccination visit to that obtained just prior to vaccination. Participants are considered a responder if the antibody increase was four-fold or greater.
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 18 Post-Vaccination
Blood samples were collected from participants prior to vaccination and at 18 months post vaccination, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The lower detection limit for the assay was 0.08 micrograms/milliliter (µg/mL), and antibody levels below this limit were recorded as 0.04 µg/mL by the laboratory. Fold rises compare IgG antibody levels at the post-vaccination visit to that obtained just prior to vaccination. Participants are considered a responder if the antibody increase was four-fold or greater.
Number of Participants With a Serum IgG Antibody to Type III GBS Post-Vaccination of 5 µg/mL or Greater at Month 0
Blood samples were collected from participants at each scheduled clinic visit beginning with Month 0 prior to vaccination, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The threshold for being considered seropositive was 5 µg/mL.
Number of Participants With a Serum IgG Antibody to Type III GBS Post-Vaccination of 5 µg/mL or Greater at Month 1 Post Vaccination
Blood samples were collected from participants at each scheduled clinic visit and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The threshold for being considered seropositive was 5 µg/mL.
Number of Participants With a Serum IgG Antibody to Type III GBS Post-Vaccination of 5 µg/mL or Greater at Month 2 Post Vaccination
Blood samples were collected from participants at each scheduled clinic visit and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The threshold for being considered seropositive was 5 µg/mL.
Number of Participants With a Serum IgG Antibody to Type III GBS Post-Vaccination of 5 µg/mL or Greater at Month 4 Post Vaccination
Blood samples were collected from participants at each scheduled clinic visit, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The threshold for being considered seropositive was 5 µg/mL.
Number of Participants With a Serum IgG Antibody to Type III GBS Post-Vaccination of 5 µg/mL or Greater at Month 6 Post Vaccination
Blood samples were collected from participants at each scheduled clinic visit, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The threshold for being considered seropositive was 5 µg/mL.
Number of Participants With a Serum IgG Antibody to Type III GBS Post-Vaccination of 5 µg/mL or Greater at Month 8 Post Vaccination
Blood samples were collected from participants at each scheduled clinic visit, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The threshold for being considered seropositive was 5 µg/mL.
Number of Participants With a Serum IgG Antibody to Type III GBS Post-Vaccination of 5 µg/mL or Greater at Month 10 Post Vaccination
Blood samples were collected from participants at each scheduled clinic visit, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The threshold for being considered seropositive was 5 µg/mL.
Number of Participants With a Serum IgG Antibody to Type III GBS Post-Vaccination of 5 µg/mL or Greater at Month 12 Post Vaccination
Blood samples were collected from participants at each scheduled clinic visit, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The threshold for being considered seropositive was 5 µg/mL.
Number of Participants With a Serum IgG Antibody to Type III GBS Post-Vaccination of 5 µg/mL or Greater at Month 14 Post Vaccination
Blood samples were collected from participants at each scheduled clinic visit, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The threshold for being considered seropositive was 5 µg/mL.
Number of Participants With a Serum IgG Antibody to Type III GBS Post-Vaccination of 5 µg/mL or Greater at Month 16 Post Vaccination
Blood samples were collected from participants at each scheduled clinic visit, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The threshold for being considered seropositive was 5 µg/mL.
Number of Participants With a Serum IgG Antibody to Type III GBS Post-Vaccination of 5 µg/mL or Greater at Month 18 Post Vaccination
Blood samples were collected from participants at each scheduled clinic visit, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The threshold for being considered seropositive was 5 µg/mL.
Number of Participants Whose Vaginal Cultures Are Type III GBS Culture Negative Throughout the Study.
Number of participants who were vaginal type III GBS negative was calculated throughout the the eighteen month post-vaccination follow-up period. Status at missed visits prior to loss to follow-up /final visit was imputed from the subsequent visit.
Number of Participants Whose Vaginal Cultures Were Type III GBS Culture Positive.
Number of participants whose vaginal swabs were type III GBS culture positive was calculated using data from the eighteen month post-vaccination follow-up period. Status at missed visits prior to loss to follow-up/final visit was imputed from the previous visit.
Number of Participants Whose Vaginal Cultures Were Persistently Type III GBS Culture Positive for Three or More Consecutive Visits
Number of vaginal GBS III culture positive for 3+ consecutive visits was calculated from the post-vaccination visits over the 18 month follow-up. Status at missed visits prior to loss to follow-up/final visit was imputed from the subsequent visit.
The Density of Type III GBS Cultured From Vaginal Swabs at Month 0
The density of type III GBS is an ordinal response with six Density Levels: negative (lowest density, Score 0); broth only (Score 1); 1+ (Score 2); 2+ (Score 3); 3+ (Score 4); and 4+ (highest density, Score 5). The number of swabs with each score was tabulated from swabs collected at Month 0 prior to vaccination.
The Density of Type III GBS Cultured From Vaginal Swabs at Month 1
The density of type III GBS is an ordinal response with six Density Levels: negative (lowest density, Score 0); broth only (Score 1); 1+ (Score 2); 2+ (Score 3); 3+ (Score 4); and 4+ (highest density, Score 5). The number of swabs with each score was tabulated from swabs collected at Month 1. Density at missed visits prior to loss to follow-up/final visit was imputed from the subsequent visit.
The Density of Type III GBS Cultured From Vaginal Swabs at Month 2
The density of type III GBS is an ordinal response with six Density Levels: negative (lowest density, Score 0); broth only (Score 1); 1+ (Score 2); 2+ (Score 3); 3+ (Score 4); and 4+ (highest density, Score 5). The number of swabs with each score was tabulated from swabs collected at Month 2. Density at missed visits prior to loss to follow-up/final visit was imputed from the subsequent visit.
The Density of Type III GBS Cultured From Vaginal Swabs at Month 4
The density of type III GBS is an ordinal response with six Density Levels: negative (lowest density, Score 0); broth only (Score 1); 1+ (Score 2); 2+ (Score 3); 3+ (Score 4); and 4+ (highest density, Score 5). The number of swabs with each score was tabulated from swabs collected at Month 4. Density at missed visits prior to loss to follow-up/final visit was imputed from the subsequent visit.
The Density of Type III GBS Cultured From Vaginal Swabs at Month 6
The density of type III GBS is an ordinal response with six Density Levels: negative (lowest density, Score 0); broth only (Score 1); 1+ (Score 2); 2+ (Score 3); 3+ (Score 4); and 4+ (highest density, Score 5). The number of swabs with each score was tabulated from swabs collected at Month 6. Density at missed visits prior to loss to follow-up/final visit was imputed from the subsequent visit.
The Density of Type III GBS Cultured From Vaginal Swabs at Month 8
The density of type III GBS is an ordinal response with six Density Levels: negative (lowest density, Score 0); broth only (Score 1); 1+ (Score 2); 2+ (Score 3); 3+ (Score 4); and 4+ (highest density, Score 5). The number of swabs with each score was tabulated from swabs collected at Month 8. Density at missed visits prior to loss to follow-up/final visit was imputed from the subsequent visit.
The Density of Type III GBS Cultured From Vaginal Swabs at Month 10
The density of type III GBS is an ordinal response with six Density Levels: negative (lowest density, Score 0); broth only (Score 1); 1+ (Score 2); 2+ (Score 3); 3+ (Score 4); and 4+ (highest density, Score 5). The number of swabs with each score was tabulated from swabs collected at Month 10. Density at missed visits prior to loss to follow-up/final visit was imputed from the subsequent visit.
The Density of Type III GBS Cultured From Vaginal Swabs at Month 12
The density of type III GBS is an ordinal response with six Density Levels: negative (lowest density, Score 0); broth only (Score 1); 1+ (Score 2); 2+ (Score 3); 3+ (Score 4); and 4+ (highest density, Score 5). The number of swabs with each score was tabulated from swabs collected at Month 12. Density at missed visits prior to loss to follow-up/final visit was imputed from the subsequent visit.
The Density of Type III GBS Cultured From Vaginal Swabs at Month 14
The density of type III GBS is an ordinal response with six Density Levels: negative (lowest density, Score 0); broth only (Score 1); 1+ (Score 2); 2+ (Score 3); 3+ (Score 4); and 4+ (highest density, Score 5). The number of swabs with each score was tabulated from swabs collected at Month 14. Density at missed visits prior to loss to follow-up/final visit was imputed from the subsequent visit.
The Density of Type III GBS Cultured From Vaginal Swabs at Month 16
The density of type III GBS is an ordinal response with six Density Levels: negative (lowest density, Score 0); broth only (Score 1); 1+ (Score 2); 2+ (Score 3); 3+ (Score 4); and 4+ (highest density, Score 5). The number of swabs with each score was tabulated from swabs collected at Month 16. Density at missed visits prior to loss to follow-up/final visit was imputed from the subsequent visit.
The Density of Type III GBS Cultured From Vaginal Swabs at Month 18
The density of type III GBS is an ordinal response with six Density Levels: negative (lowest density, Score 0); broth only (Score 1); 1+ (Score 2); 2+ (Score 3); 3+ (Score 4); and 4+ (highest density, Score 5). The number of swabs with each score was tabulated from swabs collected at Month 18. Density at missed visits prior to loss to follow-up/final visit was imputed from the subsequent visit.

Full Information

First Posted
August 5, 2005
Last Updated
January 15, 2015
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00128219
Brief Title
Prevention of GBS Colonization Via Immunity
Official Title
A Phase II Randomized, Double-Blinded, Comparative Clinical Trial for a Group B Streptococcus Serotype III-Tetanus Toxoid (GBS III-TT) Vaccine to Prevent Vaginal Acquisition of GBS Type III
Study Type
Interventional

2. Study Status

Record Verification Date
August 2009
Overall Recruitment Status
Completed
Study Start Date
July 2003 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
December 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

Brief Summary
The group B streptococcus (GBS) vaccine study is being done to see if a single vaccination with a GBS type III vaccine can stop women from getting GBS type III bacteria in the vagina. Approximately 600 women, ages 18-40, will be enrolled from the clinical sites participating in this study. Participants will be non-pregnant, sexually active (sex with a male at least once in the last 4 months), and GBS negative in the vagina or rectum at the screening visit. Participants will be randomly assigned to receive the experimental GBS type III vaccine or a licensed vaccine containing Tetanus and Diphtheria Toxoids (Td). Participants will be followed at one month, 2 months and every other month thereafter following vaccination (for vaginal and rectal swab collection and a blood draw) for 1½ years or a total of 10 post vaccination visits.
Detailed Description
Vaginal colonization is the single most important risk factor for transmission of group B Streptococcus (GBS) from mothers to neonates, resulting in neonatal sepsis and/or meningitis. The long-term goal of this study is to determine whether vaccine-induced serum antibody to type III GBS will be sufficient to prevent vaginal acquisition of type III GBS. This study is linked to Division of Microbiology and Infectious Diseases protocol 04-018. It is a randomized, double-blinded, comparative clinical trial among young (18-40 years old), non-pregnant, sexually active women who are not currently colonized vaginally or rectally with type III GBS, it will be conducted to evaluate the efficacy of a GBS type III-TT vaccine for prevention of type III GBS vaginal acquisition. The observation period for each patient will be 18 months following vaccination. The specific objectives are: enroll 600 women (previously screened within last 14 days in a GBS Screening Protocol) identified as GBS type III negative, vaginally and rectally; vaccinate 600 women randomized to a 1:1 ratio with 50 micrograms of type III GBS polysaccharide conjugated to tetanus toxoid (GBS III-TT) or licensed vaccine containing Tetanus and Diphtheria Toxoids adsorbed for adult use (Td); measure reactogenicity by subject report in a 7-day symptom diary and by 1-2 day follow-up telephone call; evaluate women at 1, 2, 4, 6, 8, 10, 12, 14, 16 and 18 months for serum antibody response. Blood will be obtained at each of these clinic follow-up visits and serum will be used to compare type III GBS specific antibody levels at baseline and follow-up; assess vaginal and rectal acquisition by GBS at months 1, 2, 4, 6, 8, 10, 12, 14, 16 and 18 months using specimens obtained at the clinic visits; compare women receiving GBS III-TT vaccine to women receiving Td vaccine with respect to the time to first vaginal culture positive for type III GBS; assess the relationship between person-level covariates, including features of the decrease of type III GBS antibody levels over time, and the time to first vaginal culture positive for type III GBS; and assess the effect of vaginal colonization by hydrogen peroxide (H2O2)-producing Lactobacillus, sexual activity, antibiotic usage, rectal colonization with GBS and demographic features as risk factors for acquisition of type III GBS, independent of serum antibody levels. The primary study endpoint will be the time to the first vaginal swab that is type III GBS culture positive, with all previous cultures negative for type III GBS, not just the immediately preceding culture. The secondary endpoints include: the proportion of vaginal swabs that are type III GBS culture positive; the proportion of subjects whose vaginal cultures are type III GBS culture negative throughout the study; the frequency of vaginal colonization with GBS serotypes Ia, Ib, II and V; the measurement of serum immunoglobulin (Ig)G antibody levels to type III GBS at 1, 2, 4, 6, 8, 10 12, 14, 16 and 18 months following vaccination; the measurement of post-vaccination antibody levels to type III GBS, stratified by pre-vaccination levels of native antibody; the frequency of local and systemic symptoms attributable to vaccination; and the density of type III GBS cultured from vaginal swabs at culture positive visits.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Beta Haemolytic Streptococcal Infection
Keywords
Group B Streptococcus, women, vaccine

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
667 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GBS III-TT
Arm Type
Experimental
Arm Description
A single dose of GBS III-TT vaccine administered intramuscularly (IM) containing 50 mcg of GBS III capsular polysaccharide and 32 mcg of tetanus toxoid.
Arm Title
Td
Arm Type
Active Comparator
Arm Description
The control group will receive a single dose of Tetanus and Diphtheria Toxoids (Td) vaccine.
Intervention Type
Biological
Intervention Name(s)
GBS III-TT
Intervention Description
50 mcg GBS Type III capsular polysaccharide conjugated to 32 mcg of tetanus toxoid. A single dose of vaccine administered by intramuscular (IM) injection in the upper arm. All subjects will receive a volume of 0.5 ml.
Intervention Type
Biological
Intervention Name(s)
Tetanus and diptheria toxoids vaccine
Intervention Description
Td vaccine is a sterile solution of alum-precipitated toxoids in isotonic sodium chloride solution. A single dose of vaccine will be administered by intramuscular (IM) injection in the upper arm. All subjects will receive a volume of 0.5 ml. Each 0.5 ml dose is formulated to contain 5 Lf (flocculation units) of tetanus toxoid and 2 Lf of diphtheria toxoid.
Primary Outcome Measure Information:
Title
The Time to First Vaginal Swab That is Type III GBS Culture Positive, With All Previous Cultures Negative for Type III GBS, Not Just the Immediately Preceding Culture.
Description
Time to first acquisition of vaginal type III GBS was calculated as time from vaccination to the mid-point of the interval of ascertainment, censored by either the end of the follow-up period, or the first of 2 or more consecutive missed visits. Vaginal type III GBS status at missed visits prior to censoring was imputed from the subsequent visit.
Time Frame
Time from vaccination to acquisition of vaginal type III GBS, up to 18 months post-vaccination.
Secondary Outcome Measure Information:
Title
Geometric Mean Concentration (GMC) of Serum Immunoglobulin G (IgG) Antibody Levels to Type III GBS Post-Vaccination.
Description
The GMC was calculated from IgG antibody to type III GBS assay results on serum specimens obtained at clinic visits during the 18 month post-vaccination follow-up period. Results at missed visits prior to loss to follow-up/final visit were not imputed.
Time Frame
Prior to and at 1, 2, 4, 6, 8, 10, 12, 14, 16, and 18 months following vaccination.
Title
Number of Participants With Any Solicited Local and Systemic Symptoms.
Description
Participants maintained a diary card to report the occurrence of solicited local and systemic symptoms for 7 days after vaccination. Participants are counted if they indicated experiencing the symptom at any severity during the reporting period.
Time Frame
Safety surveillance during the 1st 7 days.
Title
Mean Fold-Rise in Serum IgG Antibody Levels to Type III GBS Post-Vaccination
Description
Fold-rises compare the IgG antibody level at post-vaccination to that obtained just prior to vaccination, for each visit during the 18-month follow-up period. Assay results at missed visits prior to loss to follow-up/final visit were not imputed.
Time Frame
Prior to and at 1, 2, 4, 6, 8, 10, 12, 14, 16, and 18 months following vaccination.
Title
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 1 Post-Vaccination
Description
Blood samples were collected from participants prior to vaccination and at 1 month post vaccination, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The lower detection limit for the assay was 0.08 micrograms/milliliter (µg/mL), and antibody levels below this limit were recorded as 0.04 µg/mL by the laboratory. Fold rises compare IgG antibody levels at the post-vaccination visit to that obtained just prior to vaccination. Participants are considered a responder if the antibody increase was four-fold or greater.
Time Frame
Prior to and 1 month following vaccination
Title
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 2 Post-Vaccination
Description
Blood samples were collected from participants prior to vaccination and at 2 months post vaccination, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The lower detection limit for the assay was 0.08 micrograms/milliliter (µg/mL), and antibody levels below this limit were recorded as 0.04 µg/mL by the laboratory. Fold rises compare IgG antibody levels at the post-vaccination visit to that obtained just prior to vaccination. Participants are considered a responder if the antibody increase was four-fold or greater.
Time Frame
Prior to and 2 months following vaccination
Title
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 4 Post-Vaccination
Description
Blood samples were collected from participants prior to vaccination and at 4 months post vaccination, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The lower detection limit for the assay was 0.08 micrograms/milliliter (µg/mL), and antibody levels below this limit were recorded as 0.04 µg/mL by the laboratory. Fold rises compare IgG antibody levels at the post-vaccination visit to that obtained just prior to vaccination. Participants are considered a responder if the antibody increase was four-fold or greater.
Time Frame
Prior to and 4 months following vaccination
Title
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 6 Post-Vaccination
Description
Blood samples were collected from participants prior to vaccination and at 6 months post vaccination, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The lower detection limit for the assay was 0.08 micrograms/milliliter (µg/mL), and antibody levels below this limit were recorded as 0.04 µg/mL by the laboratory. Fold rises compare IgG antibody levels at the post-vaccination visit to that obtained just prior to vaccination. Participants are considered a responder if the antibody increase was four-fold or greater.
Time Frame
Prior to and 6 months following vaccination
Title
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 8 Post-Vaccination
Description
Blood samples were collected from participants prior to vaccination and at 8 month post vaccination, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The lower detection limit for the assay was 0.08 micrograms/milliliter (µg/mL), and antibody levels below this limit were recorded as 0.04 µg/mL by the laboratory. Fold rises compare IgG antibody levels at the post-vaccination visit to that obtained just prior to vaccination. Participants are considered a responder if the antibody increase was four-fold or greater.
Time Frame
Prior to and 8 month following vaccination
Title
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 10 Post-Vaccination
Description
Blood samples were collected from participants prior to vaccination and at 10 months post vaccination, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The lower detection limit for the assay was 0.08 micrograms/milliliter (µg/mL), and antibody levels below this limit were recorded as 0.04 µg/mL by the laboratory. Fold rises compare IgG antibody levels at the post-vaccination visit to that obtained just prior to vaccination. Participants are considered a responder if the antibody increase was four-fold or greater.
Time Frame
Prior to and 10 months following vaccination
Title
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 12 Post-Vaccination
Description
Blood samples were collected from participants prior to vaccination and at 12 months post vaccination, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The lower detection limit for the assay was 0.08 micrograms/milliliter (µg/mL), and antibody levels below this limit were recorded as 0.04 µg/mL by the laboratory. Fold rises compare IgG antibody levels at the post-vaccination visit to that obtained just prior to vaccination. Participants are considered a responder if the antibody increase was four-fold or greater.
Time Frame
Prior to and 12 months following vaccination
Title
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 14 Post-Vaccination
Description
Blood samples were collected from participants prior to vaccination and at 14 months post vaccination, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The lower detection limit for the assay was 0.08 micrograms/milliliter (µg/mL), and antibody levels below this limit were recorded as 0.04 µg/mL by the laboratory. Fold rises compare IgG antibody levels at the post-vaccination visit to that obtained just prior to vaccination. Participants are considered a responder if the antibody increase was four-fold or greater.
Time Frame
Prior to and 14 months following vaccination
Title
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 16 Post-Vaccination
Description
Blood samples were collected from participants prior to vaccination and at 16 months post vaccination, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The lower detection limit for the assay was 0.08 micrograms/milliliter (µg/mL), and antibody levels below this limit were recorded as 0.04 µg/mL by the laboratory. Fold rises compare IgG antibody levels at the post-vaccination visit to that obtained just prior to vaccination. Participants are considered a responder if the antibody increase was four-fold or greater.
Time Frame
Prior to and 16 months following vaccination
Title
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 18 Post-Vaccination
Description
Blood samples were collected from participants prior to vaccination and at 18 months post vaccination, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The lower detection limit for the assay was 0.08 micrograms/milliliter (µg/mL), and antibody levels below this limit were recorded as 0.04 µg/mL by the laboratory. Fold rises compare IgG antibody levels at the post-vaccination visit to that obtained just prior to vaccination. Participants are considered a responder if the antibody increase was four-fold or greater.
Time Frame
Prior to and 18 months following vaccination
Title
Number of Participants With a Serum IgG Antibody to Type III GBS Post-Vaccination of 5 µg/mL or Greater at Month 0
Description
Blood samples were collected from participants at each scheduled clinic visit beginning with Month 0 prior to vaccination, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The threshold for being considered seropositive was 5 µg/mL.
Time Frame
Month 0 prior to vaccination
Title
Number of Participants With a Serum IgG Antibody to Type III GBS Post-Vaccination of 5 µg/mL or Greater at Month 1 Post Vaccination
Description
Blood samples were collected from participants at each scheduled clinic visit and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The threshold for being considered seropositive was 5 µg/mL.
Time Frame
Month 1
Title
Number of Participants With a Serum IgG Antibody to Type III GBS Post-Vaccination of 5 µg/mL or Greater at Month 2 Post Vaccination
Description
Blood samples were collected from participants at each scheduled clinic visit and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The threshold for being considered seropositive was 5 µg/mL.
Time Frame
Month 2
Title
Number of Participants With a Serum IgG Antibody to Type III GBS Post-Vaccination of 5 µg/mL or Greater at Month 4 Post Vaccination
Description
Blood samples were collected from participants at each scheduled clinic visit, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The threshold for being considered seropositive was 5 µg/mL.
Time Frame
Month 4
Title
Number of Participants With a Serum IgG Antibody to Type III GBS Post-Vaccination of 5 µg/mL or Greater at Month 6 Post Vaccination
Description
Blood samples were collected from participants at each scheduled clinic visit, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The threshold for being considered seropositive was 5 µg/mL.
Time Frame
Month 6
Title
Number of Participants With a Serum IgG Antibody to Type III GBS Post-Vaccination of 5 µg/mL or Greater at Month 8 Post Vaccination
Description
Blood samples were collected from participants at each scheduled clinic visit, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The threshold for being considered seropositive was 5 µg/mL.
Time Frame
Month 8
Title
Number of Participants With a Serum IgG Antibody to Type III GBS Post-Vaccination of 5 µg/mL or Greater at Month 10 Post Vaccination
Description
Blood samples were collected from participants at each scheduled clinic visit, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The threshold for being considered seropositive was 5 µg/mL.
Time Frame
Month 10
Title
Number of Participants With a Serum IgG Antibody to Type III GBS Post-Vaccination of 5 µg/mL or Greater at Month 12 Post Vaccination
Description
Blood samples were collected from participants at each scheduled clinic visit, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The threshold for being considered seropositive was 5 µg/mL.
Time Frame
Month 12
Title
Number of Participants With a Serum IgG Antibody to Type III GBS Post-Vaccination of 5 µg/mL or Greater at Month 14 Post Vaccination
Description
Blood samples were collected from participants at each scheduled clinic visit, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The threshold for being considered seropositive was 5 µg/mL.
Time Frame
Month 14
Title
Number of Participants With a Serum IgG Antibody to Type III GBS Post-Vaccination of 5 µg/mL or Greater at Month 16 Post Vaccination
Description
Blood samples were collected from participants at each scheduled clinic visit, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The threshold for being considered seropositive was 5 µg/mL.
Time Frame
Month 16
Title
Number of Participants With a Serum IgG Antibody to Type III GBS Post-Vaccination of 5 µg/mL or Greater at Month 18 Post Vaccination
Description
Blood samples were collected from participants at each scheduled clinic visit, and serum was assayed with an ELISA to measure IgG antibody levels to Type III GBS. The threshold for being considered seropositive was 5 µg/mL.
Time Frame
Month 18
Title
Number of Participants Whose Vaginal Cultures Are Type III GBS Culture Negative Throughout the Study.
Description
Number of participants who were vaginal type III GBS negative was calculated throughout the the eighteen month post-vaccination follow-up period. Status at missed visits prior to loss to follow-up /final visit was imputed from the subsequent visit.
Time Frame
Every 2 months from time of vaccination up to 18 months post-vaccination.
Title
Number of Participants Whose Vaginal Cultures Were Type III GBS Culture Positive.
Description
Number of participants whose vaginal swabs were type III GBS culture positive was calculated using data from the eighteen month post-vaccination follow-up period. Status at missed visits prior to loss to follow-up/final visit was imputed from the previous visit.
Time Frame
Every 2 months from time of vaccination up to 18 months post-vaccination.
Title
Number of Participants Whose Vaginal Cultures Were Persistently Type III GBS Culture Positive for Three or More Consecutive Visits
Description
Number of vaginal GBS III culture positive for 3+ consecutive visits was calculated from the post-vaccination visits over the 18 month follow-up. Status at missed visits prior to loss to follow-up/final visit was imputed from the subsequent visit.
Time Frame
Every 2 months from time of vaccination up to 18 months post-vaccination.
Title
The Density of Type III GBS Cultured From Vaginal Swabs at Month 0
Description
The density of type III GBS is an ordinal response with six Density Levels: negative (lowest density, Score 0); broth only (Score 1); 1+ (Score 2); 2+ (Score 3); 3+ (Score 4); and 4+ (highest density, Score 5). The number of swabs with each score was tabulated from swabs collected at Month 0 prior to vaccination.
Time Frame
Month 0
Title
The Density of Type III GBS Cultured From Vaginal Swabs at Month 1
Description
The density of type III GBS is an ordinal response with six Density Levels: negative (lowest density, Score 0); broth only (Score 1); 1+ (Score 2); 2+ (Score 3); 3+ (Score 4); and 4+ (highest density, Score 5). The number of swabs with each score was tabulated from swabs collected at Month 1. Density at missed visits prior to loss to follow-up/final visit was imputed from the subsequent visit.
Time Frame
Month 1
Title
The Density of Type III GBS Cultured From Vaginal Swabs at Month 2
Description
The density of type III GBS is an ordinal response with six Density Levels: negative (lowest density, Score 0); broth only (Score 1); 1+ (Score 2); 2+ (Score 3); 3+ (Score 4); and 4+ (highest density, Score 5). The number of swabs with each score was tabulated from swabs collected at Month 2. Density at missed visits prior to loss to follow-up/final visit was imputed from the subsequent visit.
Time Frame
Month 2
Title
The Density of Type III GBS Cultured From Vaginal Swabs at Month 4
Description
The density of type III GBS is an ordinal response with six Density Levels: negative (lowest density, Score 0); broth only (Score 1); 1+ (Score 2); 2+ (Score 3); 3+ (Score 4); and 4+ (highest density, Score 5). The number of swabs with each score was tabulated from swabs collected at Month 4. Density at missed visits prior to loss to follow-up/final visit was imputed from the subsequent visit.
Time Frame
Month 4
Title
The Density of Type III GBS Cultured From Vaginal Swabs at Month 6
Description
The density of type III GBS is an ordinal response with six Density Levels: negative (lowest density, Score 0); broth only (Score 1); 1+ (Score 2); 2+ (Score 3); 3+ (Score 4); and 4+ (highest density, Score 5). The number of swabs with each score was tabulated from swabs collected at Month 6. Density at missed visits prior to loss to follow-up/final visit was imputed from the subsequent visit.
Time Frame
Month 6
Title
The Density of Type III GBS Cultured From Vaginal Swabs at Month 8
Description
The density of type III GBS is an ordinal response with six Density Levels: negative (lowest density, Score 0); broth only (Score 1); 1+ (Score 2); 2+ (Score 3); 3+ (Score 4); and 4+ (highest density, Score 5). The number of swabs with each score was tabulated from swabs collected at Month 8. Density at missed visits prior to loss to follow-up/final visit was imputed from the subsequent visit.
Time Frame
Month 8
Title
The Density of Type III GBS Cultured From Vaginal Swabs at Month 10
Description
The density of type III GBS is an ordinal response with six Density Levels: negative (lowest density, Score 0); broth only (Score 1); 1+ (Score 2); 2+ (Score 3); 3+ (Score 4); and 4+ (highest density, Score 5). The number of swabs with each score was tabulated from swabs collected at Month 10. Density at missed visits prior to loss to follow-up/final visit was imputed from the subsequent visit.
Time Frame
Month 10
Title
The Density of Type III GBS Cultured From Vaginal Swabs at Month 12
Description
The density of type III GBS is an ordinal response with six Density Levels: negative (lowest density, Score 0); broth only (Score 1); 1+ (Score 2); 2+ (Score 3); 3+ (Score 4); and 4+ (highest density, Score 5). The number of swabs with each score was tabulated from swabs collected at Month 12. Density at missed visits prior to loss to follow-up/final visit was imputed from the subsequent visit.
Time Frame
Month 12
Title
The Density of Type III GBS Cultured From Vaginal Swabs at Month 14
Description
The density of type III GBS is an ordinal response with six Density Levels: negative (lowest density, Score 0); broth only (Score 1); 1+ (Score 2); 2+ (Score 3); 3+ (Score 4); and 4+ (highest density, Score 5). The number of swabs with each score was tabulated from swabs collected at Month 14. Density at missed visits prior to loss to follow-up/final visit was imputed from the subsequent visit.
Time Frame
Month 14
Title
The Density of Type III GBS Cultured From Vaginal Swabs at Month 16
Description
The density of type III GBS is an ordinal response with six Density Levels: negative (lowest density, Score 0); broth only (Score 1); 1+ (Score 2); 2+ (Score 3); 3+ (Score 4); and 4+ (highest density, Score 5). The number of swabs with each score was tabulated from swabs collected at Month 16. Density at missed visits prior to loss to follow-up/final visit was imputed from the subsequent visit.
Time Frame
Month 16
Title
The Density of Type III GBS Cultured From Vaginal Swabs at Month 18
Description
The density of type III GBS is an ordinal response with six Density Levels: negative (lowest density, Score 0); broth only (Score 1); 1+ (Score 2); 2+ (Score 3); 3+ (Score 4); and 4+ (highest density, Score 5). The number of swabs with each score was tabulated from swabs collected at Month 18. Density at missed visits prior to loss to follow-up/final visit was imputed from the subsequent visit.
Time Frame
Month 18

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Participated in and completed the group B Streptococcus (GBS) Screening Protocol Non-pregnant women Aged 18-40 years at time of the screening protocol Currently sexually active at time of enrollment (sex with a male at least once in the last 4 months) Current use of effective birth control methods and stated intention to use the method for at least the next 30 days Provision of written informed consent Intention to stay in the geographical area for the next 18 months Access to telephone Exclusion Criteria: Group B Streptococcus (GBS) positive by culture (vaginal and/or rectal), or culture positive for streptococcal strains that cross-react with GBS typing sera (vaginal and/or rectal). Pregnancy (all women will receive a urine pregnancy prior to vaccination). Any condition which in the opinion of the investigator would pose a health risk to the subject or interfere with the evaluation of the vaccine. Serious underlying disease, which is known at the time of vaccination (including: immunodeficiency, active or chronic hepatitis, immunosuppressive conditions which require systemic steroid therapy, or treatment for a malignancy during the past year). Receipt of any vaccine, blood product, or experimental medicine within the past 30 days with the exception of a licensed inactivated influenza vaccine. Plans to receive any vaccine, blood product, or experimental medicine in the next 30 days with the exception of a licensed inactivated influenza vaccine. Use of any antimicrobial agent(s) (vaginal or systemic) for treatment of any condition within 7 days prior to study enrollment (including: Monistat, Gyne-Lotrimin, et cetera ) History of hypersensitivity to tetanus toxoid vaccine. Tetanus toxoid immunization within the previous 12 months. Previous participation in a study in which participants received tetanus toxoid vaccine or vaccine against Group B Streptococcus. Spontaneous or surgical menopause. Nursing mother. Hypersensitivity to thimerosal.
Facility Information:
Facility Name
Medical College of Georgia
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
Magee-Womens Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Planned Parenthood of Houston and Southeast Texas, Inc.
City
Houston
State/Province
Texas
ZIP/Postal Code
77004
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
30281066
Citation
Hillier SL, Ferrieri P, Edwards MS, Ewell M, Ferris D, Fine P, Carey V, Meyn L, Hoagland D, Kasper DL, Paoletti LC, Hill H, Baker CJ. A Phase 2, Randomized, Control Trial of Group B Streptococcus (GBS) Type III Capsular Polysaccharide-tetanus Toxoid (GBS III-TT) Vaccine to Prevent Vaginal Colonization With GBS III. Clin Infect Dis. 2019 May 30;68(12):2079-2086. doi: 10.1093/cid/ciy838.
Results Reference
derived

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Prevention of GBS Colonization Via Immunity

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