Beta Haemolytic Streptococcal InfectionPhase 2NCT00128219
Prevention of GBS Colonization Via Immunity
A Phase 2 study testing GBS III-TT and Tetanus and diptheria toxoids vaccine in people with Beta Haemolytic Streptococcal Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Beta Haemolytic Streptococcal Infection
- What is being tested?
- GBS III-TT and Tetanus and diptheria toxoids vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 667 participants
- Where
- 3 sitesUnited States
- Study dates
- Jul 2003to Dec 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Medical College of Georgia
Augusta, Georgia, 30912
Planned Parenthood of Houston and Southeast Texas, Inc.
Houston, Texas, 77004
Magee-Womens Hospital
Pittsburgh, Pennsylvania, 15213
About this study
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
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.
Read the 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.
- Conditions
- Beta Haemolytic Streptococcal Infection
- Being tested
- GBS III-TT, Tetanus and diptheria toxoids vaccine
- Keywords
- Group B Streptococcus, women, vaccine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GBS III-TTBiological
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.
Tetanus and diptheria toxoids vaccineBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| GBS III-TT | Experimental | 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. Receives: Biological: GBS III-TT |
| Td | Active comparator | The control group will receive a single dose of Tetanus and Diphtheria Toxoids (Td) vaccine. Receives: Biological: Tetanus and diptheria toxoids vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Time from vaccination to acquisition of vaginal type III GBS, up to 18 months post-vaccination.
Secondary outcomes (38)
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.
Measured: Prior to and at 1, 2, 4, 6, 8, 10, 12, 14, 16, and 18 months following vaccination.
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.
Measured: Safety surveillance during the 1st 7 days.
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.
Measured: Prior to and at 1, 2, 4, 6, 8, 10, 12, 14, 16, and 18 months following vaccination.
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.
Measured: Prior to and 1 month following vaccination
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.
Measured: Prior to and 2 months following vaccination
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.
Measured: Prior to and 4 months following vaccination
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.
Measured: Prior to and 6 months following vaccination
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.
Measured: Prior to and 8 month following vaccination
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.
Measured: Prior to and 10 months following vaccination
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.
Measured: Prior to and 12 months following vaccination
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.
Measured: Prior to and 14 months following vaccination
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.
Measured: Prior to and 16 months following vaccination
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.
Measured: Prior to and 18 months following vaccination
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.
Measured: Month 0 prior to vaccination
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.
Measured: Month 1
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.
Measured: Month 2
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.
Measured: Month 4
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.
Measured: Month 6
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.
Measured: Month 8
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.
Measured: Month 10
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.
Measured: Month 12
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.
Measured: Month 14
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.
Measured: Month 16
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.
Measured: Month 18
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.
Measured: Every 2 months from time of vaccination up to 18 months post-vaccination.
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.
Measured: Every 2 months from time of vaccination up to 18 months post-vaccination.
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.
Measured: Every 2 months from time of vaccination up to 18 months post-vaccination.
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.
Measured: Month 0
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.
Measured: Month 1
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.
Measured: Month 2
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.
Measured: Month 4
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.
Measured: Month 6
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.
Measured: Month 8
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.
Measured: Month 10
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.
Measured: Month 12
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.
Measured: Month 14
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.
Measured: Month 16
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.
Measured: Month 18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2005 (estimated)
- Study startJul 2003
- Primary completionDec 2008
- Study completionDec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Beta Haemolytic Streptococcal InfectionStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 667 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00128219
- Sponsor's protocol ID
- 02-015
- Status last verified
- Aug 2009
- First submitted
- 5 Aug 2005
- Last updated
- 27 Jan 2015
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 30281066
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00128219
- Acronym / sponsor ID
- 02-015
- Conditions
- Beta Haemolytic Streptococcal Infection
- Keywords
- Group B Streptococcus, women, vaccine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 667 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Jul 2003
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 9 Aug 2005 (estimated)
- Results
- Posted 5 Jul 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GBS III-TT | Experimental | Biological: GBS III-TTA single dose of GBS III-TT vaccine administered intramuscularly (IM) containing 50 mcg of GBS III capsular polysaccharide and 32 mcg of tetanus toxoid. |
| Td | Active comparator | Biological: Tetanus and diptheria toxoids vaccineThe control group will receive a single dose of Tetanus and Diphtheria Toxoids (Td) vaccine. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GBS III-TT50 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. | Biological | GBS III-TT |
| Tetanus and diptheria toxoids vaccineTd 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. | Biological | Td |
Primary outcome
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.
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.
38 secondary outcomes
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.
Number of Participants With Any Solicited Local and Systemic Symptoms.
Time frame: Safety surveillance during the 1st 7 days.
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.
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 1 Post-Vaccination
Time frame: Prior to and 1 month following vaccination
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 2 Post-Vaccination
Time frame: Prior to and 2 months following vaccination
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 4 Post-Vaccination
Time frame: Prior to and 4 months following vaccination
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 6 Post-Vaccination
Time frame: Prior to and 6 months following vaccination
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 8 Post-Vaccination
Time frame: Prior to and 8 month following vaccination
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 10 Post-Vaccination
Time frame: Prior to and 10 months following vaccination
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 12 Post-Vaccination
Time frame: Prior to and 12 months following vaccination
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 14 Post-Vaccination
Time frame: Prior to and 14 months following vaccination
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 16 Post-Vaccination
Time frame: Prior to and 16 months following vaccination
Number of Participants With a Four-Fold or Greater Rise in Serum IgG Antibody to Type III GBS at Month 18 Post-Vaccination
Time frame: Prior to and 18 months following vaccination
Number of Participants With a Serum IgG Antibody to Type III GBS Post-Vaccination of 5 µg/mL or Greater at Month 0
Time frame: Month 0 prior to vaccination
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
Time frame: Month 1
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
Time frame: Month 2
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
Time frame: Month 4
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
Time frame: Month 6
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
Time frame: Month 8
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
Time frame: Month 10
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
Time frame: Month 12
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
Time frame: Month 14
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
Time frame: Month 16
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
Time frame: Month 18
Number of Participants 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.
Number of Participants Whose Vaginal Cultures Were Type III GBS Culture Positive.
Time frame: Every 2 months from time of vaccination up to 18 months post-vaccination.
Number of Participants 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.
The Density of Type III GBS Cultured From Vaginal Swabs at Month 0
Time frame: Month 0
The Density of Type III GBS Cultured From Vaginal Swabs at Month 1
Time frame: Month 1
The Density of Type III GBS Cultured From Vaginal Swabs at Month 2
Time frame: Month 2
The Density of Type III GBS Cultured From Vaginal Swabs at Month 4
Time frame: Month 4
The Density of Type III GBS Cultured From Vaginal Swabs at Month 6
Time frame: Month 6
The Density of Type III GBS Cultured From Vaginal Swabs at Month 8
Time frame: Month 8
The Density of Type III GBS Cultured From Vaginal Swabs at Month 10
Time frame: Month 10
The Density of Type III GBS Cultured From Vaginal Swabs at Month 12
Time frame: Month 12
The Density of Type III GBS Cultured From Vaginal Swabs at Month 14
Time frame: Month 14
The Density of Type III GBS Cultured From Vaginal Swabs at Month 16
Time frame: Month 16
The Density of Type III GBS Cultured From Vaginal Swabs at Month 18
Time frame: Month 18
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30281066Hillier 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GBS III-TT and Tetanus and diptheria toxoids vaccine in people with Beta Haemolytic Streptococcal Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jul 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00128219, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2015; AzTrials last refreshed its copy on 6 Nov 2026.