Safety and Immunogenicity of a Group B Streptococcus Vaccine in Non Pregnant and Pregnant Women 18-40 Years of Age

Study Overview
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Brief Summary
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This study will evaluate the safety and immunogenicity of a Group B Streptococcus vaccine at one dose in healthy non pregnant women and then in three different doses in healthy pregnant women.

Official Title
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A Phase Ib/II Randomized, Observer-Blind, Controlled, Single Centre Study of a Trivalent Group B Streptococcus Vaccine in Healthy Non-Pregnant Women Leading Into a Dose-Ranging Study in Pregnant Women in South Africa

Conditions
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Streptococcal Infections

Intervention / Treatment
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* Biological: Group B Streptococcus Trivalent Vaccine - 20/20/20 μg
* Other: Saline solution
* Biological: Group B Streptococcus Trivalent Vaccine - 0.5/0.5/0.5 μg
* Biological: Group B Streptococcus Trivalent Vaccine - 2.5/2.5/2.5 μg
* Biological: Group B Streptococcus Trivalent Vaccine - 5/5/5 μg
* Other: saline solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Group 1 (Non Pregnant Women): Healthy females 18-40 years of age inclusive. Group 2 (Healthy Pregnant Women): Healthy pregnant women 18-40 yrs of age (between 28-35 weeks gestation) Exclusion Criteria: Group 1 (Non Pregnant Women): Pregnant or nursing; History of severe allergy to previous vaccines; Known HIV positive Group 2 (Healthy Pregnant Women): History of severe allergy to previous vaccines; Known HIV positive

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1: GBS Trivalent Vaccine with aluminium - 20/20/20 μg<br>Non-pregnant women who received two injections of 20/20/20 μg dose of Group B Streptococcus (GBS) Trivalent Vaccine with aluminum. | Biological: Group B Streptococcus Trivalent Vaccine - 20/20/20 μg<br>* Subjects received two injections of 20/20/20 μg dose of Group B Streptococcus (GBS) Trivalent Vaccine with aluminum.<br>|
| Placebo Comparator: 2: Placebo - Sterile saline<br>Non-Pregnant Women who received two injection of saline solution. | Other: Saline solution<br>* Subjects received two injection of saline solution.<br>|
| Experimental: 3: GBS Trivalent Vaccine - 0.5/0.5/0.5 µg<br>Pregnant women who received one injection of 0.5/0.5/0.5 μg dose of non adjuvanted Group B Streptococcus (GBS) Trivalent Vaccine. | Biological: Group B Streptococcus Trivalent Vaccine - 0.5/0.5/0.5 μg<br>* Subjects received one injection of 0.5/0.5/0.5 μg dose of non adjuvanted Group B Streptococcus (GBS) Trivalent Vaccine.<br>|
| Experimental: 4: GBS Trivalent Vaccine - 2.5/2.5/2.5 µg<br>Pregnant Women who received one injection of 2.5/2.5/2.5 μg dose of non adjuvanted Group B Streptococcus (GBS) Trivalent Vaccine. | Biological: Group B Streptococcus Trivalent Vaccine - 2.5/2.5/2.5 μg<br>* Subjects received one injection of 2.5/2.5/2.5 μg dose of non adjuvanted Group B Streptococcus (GBS) Trivalent Vaccine.<br>|
| Experimental: 5: GBS Trivalent Vaccine - 5/5/5 µg<br>Pregnant women who received one injection of 5/5/5 μg dose of non adjuvanted Group B Streptococcus (GBS) Trivalent Vaccine. | Biological: Group B Streptococcus Trivalent Vaccine - 5/5/5 μg<br>* Subjects received one injection of 5/5/5 μg dose of non adjuvanted Group B Streptococcus (GBS) Trivalent Vaccine.<br>|
| Placebo Comparator: 6: Placebo - Sterile saline<br>Pregnant Women who received one injection of saline solution. | Other: saline solution<br>* Subjects received one injection of saline solution.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentages of Non-pregnant Subjects With Antibody Concentrations Above a Defined Threshold at One Month After the Second Vaccination. | The percentages of non-pregnant subjects with antibody concentrations above a defined threshold per serotype after the administration of two vaccine doses administered one month apart. Defined thresholds for antibody concentrations, which exceed pre-defined serotype specific ELISA values are 1, 2, 3, 5 and 8 μg/mL. | Day 61, one month after the second vaccination | 
| Antibody Geometric Mean Concentrations (GMC) in Non-pregnant Women at One Month After the Second Vaccination. | Antibody GMC per serotype in non-pregnant women after receiving two doses of the study vaccine administered one month apart . | Day 61, one month after the second vaccination | 
| The Percentages of Maternal Subjects With Antibody Concentrations Above a Defined Threshold at Day of Delivery. | The percentages of maternal subjects with antibody concentrations above a defined threshold per serotype following the administration of one of three different doses of the study vaccine or placebo.Antibody concentrations which exceed pre-defined serotype specific ELISA values are 1, 2, 3, 5 and 8 μg/mL. | Day of delivery | 
| Antibody GMC in Maternal Subjects at Day of Delivery | Antibody GMC per serotype in maternal subjects at day of delivery following one administration of one of three different doses of the study vaccine or placebo are reported. | Day of delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentages of Maternal Subjects With Antibody Concentrations Above a Defined Threshold Per Serotype at One Month After Vaccination. | The percentages of maternal subjects with antibody concentrations above a defined threshold per serotype at one month after the administration of one of three different doses of the study vaccine or placebo. Antibody concentrations which exceed pre-defined serotype specific ELISA values are 1, 2, 3, 5 and 8 μg/mL. | Day 31, one month after vaccination | 
| Antibody GMC Per Serotype in Maternal Subjects at One Month After Vaccination | Antibody GMC per serotype in maternal subjects at one month after the administration of one of three different doses of the study vaccine or placebo. | day 31 | 
| The Percentage of Non-pregnant Subjects With Antibody Concentrations Above a Defined Threshold at One Year After the First Vaccination. | The percentage of non-pregnant subjects with antibody concentrations above a defined threshold per serotype after the administration of two vaccine doses one month apart. Antibody concentrations which exceed pre-defined serotype specific ELISA values are 1, 2, 3, 5 and 8 mcg/mL. | Day 361, one year after the first vaccination | 
| Antibody GMC in Non-pregnant Subjects at One Year After the First Vaccination | Antibody GMC per serotype in non-pregnant subjects after receiving two doses of the study vaccine administered one month apart, at one year after first vaccination. | Day 361, one year after the first vaccination | 
| Number of Non-pregnant Subjects Reporting Solicited and Unsolicited Adverse Events | Number of non-pregnant subjects reporting solicited and unsolicited adverse events following 2 injections (1 month apart) of the trivalent GBS vaccine at a dose of 20/20/20 μg with aluminum at one month after second vaccination are reported. | Day 61 | 
| Number of Maternal Subjects Reporting Solicited and Unsolicited Adverse Events | Number of maternal subjects reporting solicited and unsolicited adverse events following the administration of either one of three different doses of the study vaccine or placebo. | From day 1 to one year after delivery | 
| Antibody GMC Per Serotype at Different Time Points in Infants | Antibody GMC per serotype on the day of birth, at 6 weeks and 3 months of age in infants born from women who received either one of three different doses of the study vaccine or placebo. | Day 4, day 43 and day 91 after birth | 
| Number of Infants Reporting Serious Adverse Events | Number of infants born from women who received either one of three different doses of the study vaccine or placebo who reported serious adverse events | one year after birth | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Group B streptococcus, GBS, Vaccine, Prevention of group B streptococcus infection