Beta Haemolytic Streptococcal Infection Clinical Trial
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.
| Status | Completed |
| Enrollment | 667 |
| Est. completion date | December 2008 |
| Est. primary completion date | December 2008 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | Female |
| Age group | 18 Years to 40 Years |
| Eligibility |
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. |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention
| Country | Name | City | State |
|---|---|---|---|
| United States | Medical College of Georgia | Augusta | Georgia |
| United States | Planned Parenthood of Houston and Southeast Texas, Inc. | Houston | Texas |
| United States | Magee-Womens Hospital | Pittsburgh | Pennsylvania |
| Lead Sponsor | Collaborator |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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. | Time from vaccination to acquisition of vaginal type III GBS, up to 18 months post-vaccination. | No |
| Secondary | 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. | Prior to and at 1, 2, 4, 6, 8, 10, 12, 14, 16, and 18 months following vaccination. | No |
| Secondary | 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. | Safety surveillance during the 1st 7 days. | Yes |
| Secondary | 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. | Prior to and at 1, 2, 4, 6, 8, 10, 12, 14, 16, and 18 months following vaccination. | No |
| Secondary | 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. | Prior to and 1 month following vaccination | No |
| Secondary | 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. | Prior to and 2 months following vaccination | No |
| Secondary | 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. | Prior to and 4 months following vaccination | No |
| Secondary | 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. | Prior to and 6 months following vaccination | No |
| Secondary | 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. | Prior to and 8 month following vaccination | No |
| Secondary | 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. | Prior to and 10 months following vaccination | No |
| Secondary | 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. | Prior to and 12 months following vaccination | No |
| Secondary | 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. | Prior to and 14 months following vaccination | No |
| Secondary | 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. | Prior to and 16 months following vaccination | No |
| Secondary | 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. | Prior to and 18 months following vaccination | No |
| Secondary | 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. | Month 0 prior to vaccination | No |
| Secondary | 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. | Month 1 | No |
| Secondary | 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. | Month 2 | No |
| Secondary | 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. | Month 4 | No |
| Secondary | 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. | Month 6 | No |
| Secondary | 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. | Month 8 | No |
| Secondary | 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. | Month 10 | No |
| Secondary | 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. | Month 12 | No |
| Secondary | 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. | Month 14 | No |
| Secondary | 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. | Month 16 | No |
| Secondary | 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. | Month 18 | No |
| Secondary | 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. | Every 2 months from time of vaccination up to 18 months post-vaccination. | No |
| Secondary | 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. | Every 2 months from time of vaccination up to 18 months post-vaccination. | No |
| Secondary | 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. | Every 2 months from time of vaccination up to 18 months post-vaccination. | No |
| Secondary | 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. | Month 0 | No |
| Secondary | 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. | Month 1 | No |
| Secondary | 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. | Month 2 | No |
| Secondary | 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. | Month 4 | No |
| Secondary | 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. | Month 6 | No |
| Secondary | 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. | Month 8 | No |
| Secondary | 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. | Month 10 | No |
| Secondary | 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. | Month 12 | No |
| Secondary | 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. | Month 14 | No |
| Secondary | 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. | Month 16 | No |
| Secondary | 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. | Month 18 | No |