Prevention of GBS Colonization Via Immunity

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00128219
First received: August 5, 2005
Last updated: June 7, 2012
Last verified: August 2009
  Purpose

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.


Condition Intervention Phase
Streptococcus Group B
Biological: Td
Biological: GBS III-TT
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

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 Frame: Time from vaccination to acquisition of vaginal type III GBS, up to 18 months post-vaccination. ] [ Designated as safety issue: No ]
    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. [ Time Frame: Prior to and at 1, 2, 4, 6, 8, 10, 12, 14, 16, and 18 months following vaccination. ] [ Designated as safety issue: No ]
    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 Subjects With Any Solicited Local and Systemic Symptoms. [ Time Frame: Safety surveillance during the 1st 7 days. ] [ Designated as safety issue: Yes ]
    Subjects maintained a diary card to report the occurrence of solicited local and systemic symptoms for 7 days after vaccination. Subjects are counted if they indicated experiencing the symptom at any severity during the reporting period.

  • The Density of Type III GBS Cultured From Vaginal Swabs. [ Time Frame: Every 2 months from time to vaccination up to 18 months post-vaccination. ] [ Designated as safety issue: No ]
    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). Density at missed visits prior to loss to follow-up/final visit was imputed from the subsequent visit

  • Mean Fold-Rise in Serum IgG Antibody Levels to Type III GBS Post-Vaccination [ Time Frame: Prior to and at 1, 2, 4, 6, 8, 10, 12, 14, 16, and 18 months following vaccination. ] [ Designated as safety issue: No ]
    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.

  • Percent Responders - Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS Post-Vaccination [ Time Frame: At 1, 2, 4, 6, 8, 10, 12, 14, 16 and 18 months post-vaccination. ] [ Designated as safety issue: No ]
    Four-fold or greater rises compare IgG antibody levels at each post-vaccination visit during the 18-month follow-up period to that obtained just prior to vaccination. Assay results at missed visits prior to loss to follow-up/final visit were not imputed.

  • Percent Responders - 5 µg/ml or Greater Serum IgG Antibody to Type III GBS Post-Vaccination [ Time Frame: Prior to and at 1, 2, 4, 6, 8, 10, 12, 14, 16, and 18 months post vaccination ] [ Designated as safety issue: No ]
    Percent responders were the proportion of subjects with >=5 µg/ml in serum IgG antibody levels, assessed at each post-vaccination visit. Assay results at missed visits prior to loss to follow-up/final visit were not imputed.

  • Number of Subjects Whose Vaginal Cultures Are Type III GBS Culture Negative Throughout the Study. [ Time Frame: Every 2 months from time of vaccination up to 18 months post-vaccination. ] [ Designated as safety issue: No ]
    Number of subjects 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 Subjects Whose Vaginal Cultures Were Type III GBS Culture Positive. [ Time Frame: Every 2 months from time of vaccination up to 18 months post-vaccination. ] [ Designated as safety issue: No ]
    Number of subjects 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 Subjects Whose Vaginal Cultures Were Persistently Type III GBS Culture Positive for Three or More Consecutive Visits [ Time Frame: Every 2 months from time of vaccination up to 18 months post-vaccination. ] [ Designated as safety issue: No ]
    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.


Enrollment: 667
Study Start Date: July 2003
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GBS III-TT
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.
Biological: GBS III-TT
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.
Active Comparator: Td
The control group will receive a single dose of Tetanus and Diphtheria Toxoids (Td) vaccine.
Biological: Td
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00128219

Locations
United States, Georgia
Medical College of Georgia
Augusta, Georgia, United States, 30912
United States, Pennsylvania
Magee-Womens Hospital
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
Planned Parenthood of Houston and Southeast Texas, Inc.
Houston, Texas, United States, 77004
Sponsors and Collaborators
  More Information

No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00128219     History of Changes
Other Study ID Numbers: 02-015
Study First Received: August 5, 2005
Results First Received: August 3, 2009
Last Updated: June 7, 2012
Health Authority: United States: Federal Government
United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Group B Streptococcus, women, vaccine

ClinicalTrials.gov processed this record on October 20, 2014