Safety and Immunogenicity of a Group B Streptococcus Vaccine in Healthy Women

A Phase Ib Randomized, Observer-Blind, Controlled, Single Center, Dose-Ranging Study of a Group B Streptococcus Vaccine in Healthy Women 18-40 Years of Age

This study will evaluate the safety and immunogenicity of a Group B Streptococcus vaccine.

Study Overview

• Status: Completed
• Conditions: Group B Streptococcus
• Intervention / Treatment: Biological: Group B streptococcus (GBS) vaccine- low dose; Biological: Group B streptococcus (GBS) vaccine- High dose; Biological: Placebo- Saline

• Study Type: Interventional
• Enrollment (Actual): 678
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Healthy females 18-40 years of age inclusive.

Exclusion Criteria:

• Individuals who are pregnant or nursing.
• Individuals who have had a previous immunization with a vaccine containing streptococcus antigens or any vaccine within 30 days of enrollment through 30 days of study completion.
• Individuals with a history of severe allergic reactions after previous vaccination
• Individuals with designated blood tests that are not within normal range

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5 µg_No Adj; Subjects received either 1 or 2 doses of active vaccine (5 µg) without any adjuvant	Biological: Group B streptococcus (GBS) vaccine- low dose
Experimental: 20 µg_No Adj; Subjects received either 1 or 2 doses of active vaccine (20 µg) without any adjuvant.	Biological: Group B streptococcus (GBS) vaccine- High dose
Experimental: 5 µg_Alum; Subjects received either 1 or 2 doses of active vaccine (5 µg) with Alum adjuvant.	Biological: Group B streptococcus (GBS) vaccine- low dose
Experimental: 20 µg_Alum; Subjects received either 1 or 2 doses of active vaccine (5 µg) with Alum adjuvant.	Biological: Group B streptococcus (GBS) vaccine- High dose
Experimental: 5 µg_MF59-H; Subjects received either 1 or 2 doses of active vaccine (5 µg) adjuvanted with 4.87 mg of MF59	Biological: Group B streptococcus (GBS) vaccine- low dose
Experimental: 20 µg_MF59-H; Subjects received either 1 or 2 doses of active vaccine (20 µg) adjuvanted with 4.87 mg of MF59	Biological: Group B streptococcus (GBS) vaccine- High dose
Experimental: 5 µg_MF59-F; Subjects received either 1 or 2 doses of active vaccine (5 µg) adjuvanted with 9.75 mg of MF59	Biological: Group B streptococcus (GBS) vaccine- low dose
Experimental: 20 µg_MF59-F; Subjects received either 1 or 2 doses of active vaccine (20 µg) adjuvanted with 9.75 mg of MF59	Biological: Group B streptococcus (GBS) vaccine- High dose
Placebo Comparator: Placebo; Subjects received 2 injections of placebo administered 1 month apart	Biological: Placebo- Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Achieving Specific Thresholds of Antibody Concentrations for Subjects in Enrollment Group 1	The percentage of subjects achieving a specific threshold of antibody concentrations of ≥ 0.5 µg/mL as determined by ELISA at day 61 across cohorts 1 and 2 for potential use in pregnant women.	Day 1 and Day 61
Geometric Mean Concentrations of Serum Anti-GBS IgG Antibody Levels by Serotype at Day 61	Serotype-specific (Ia, Ib & III) group B streptococcus (GBS) IgG antibody levels in healthy subjects for potential use in pregnant woman was assessed in terms of Geometric Mean Concentrations (GMCs) at Day 61 in cohorts 1 and 2.	Day 1 and Day 61
Geometric Mean Ratios of Serum Group B Streptococcus IgG Antibody Levels By Serotype	Geometric mean ratios (GMRs) relative to baseline (Day 1) of serotype-specific (Ia, Ib, III) GBS IgG antibody levels measured at Day 61 for subjects across cohorts 1 and 2.	Day 61/Day 1
Percentage of Subjects Achieving Specific Thresholds of Antibody Concentrations for Subjects in Enrollment Groups 1 & 2	The percentage of subjects achieving a specific threshold of antibody concentrations of ≥ 0.5 µg/mL at day 361 across all the cohorts for potential use in non-pregnant women.	Day 1 and Day 361
Geometric Mean Concentrations of Serum Anti-GBS IgG Antibody Levels by Serotype at Day 361	Serotype-specific (Ia, Ib & III) GBS IgG antibody levels in healthy subjects for potential use in non-pregnant woman was assessed in terms of GMCs at Day 361 across all cohorts.	Day 1 and Day 361
Geometric Mean Ratios of Serum Group B Streptococcus IgG Antibody Levels By Serotype at Day 361	GMRs relative to baseline (Day 1) of serotype-specific (Ia, Ib, III) GBS IgG antibody levels in healthy subjects for potential use in non-pregnant women, measured at Day 361 across all cohorts.	Day 1 and day 361

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Reporting Solicited Adverse Events (AEs) After Receiving the GBS Trivalent Vaccine in Enrollment Group 1	Safety was assessed in terms of number of participants reporting solicited local and systemic adverse events after receiving trivalent GBS vaccine from day 1 to day 7 for subjects across cohorts 1 and 2.	Day 1 to Day 7
Number of Participants Reporting Solicited AEs After Receiving the GBS Trivalent Vaccine in Enrollment Group 2	Safety was assessed in terms of number of participants reporting solicited local and systemic adverse events after receiving GBS vaccine from day 1 to day 7 for subjects in cohorts 3 and 4.	Day 1 to Day 7
Number of Participants Reporting Unsolicited AE After Receiving GBS Trivalent Vaccine in Enrollment Group 1	Safety was assessed in terms of number of participants with unsolicited AEs after receiving GBS trivalent vaccine, reported from day 1 to day 721 across subjects in cohorts 1 and 2.	Day 1 through Day 721
Number of Participants Reporting Unsolicited AE After Receiving GBS Trivalent Vaccine in Enrollment Group 2	Safety was assessed in terms of number of participants with unsolicited AEs after receiving GBS trivalent vaccine, reported from day 1 to day 721 across subjects in cohorts 3 and 4.	Day 1 through Day 721
Persistence of Antibody Response in Terms of Geometric Mean Concentrations by Serotype for Subjects in Enrollment Group 1	The persistence of Serotype-specific (Ia, Ib & III) GBS IgG antibody response was assessed by comparing ELISA responses in terms of GMCs at day 721 after the first injection for subjects enrolled in cohorts 1 and 2.	Day 1 and Day 721
Persistence of Antibody Response in Terms of Geometric Mean Concentrations by Serotype in Subjects in Enrollment Group 2	The persistence of Serotype-specific (Ia, Ib & III) GBS IgG antibody response assessed by comparing ELISA responses in terms of GMCs at day 721 after the first injection for subjects enrolled in cohort 3 and 4.	Day 1 and Day 721
Geometric Mean Ratios of Serum GBS IgG Antibody Levels By Serotype for Subjects in Enrollment Group 1	GMR was calculated at Day 721 relative to baseline (Day 1) of serotype-specific (Ia, Ib, III) GBS IgG antibody levels across all cohorts 1 and 2.	Day 1 and Day 721
Geometric Mean Ratios of Serum GBS IgG Antibody Levels By Serotype for Subjects in Enrollment Group 2	GMR was calculated at Day 721 relative to baseline (Day 1) of serotype-specific (Ia, Ib, III) GBS IgG antibody levels across cohorts 3 and 4.	Day 1 and Day 721

Collaborators and Investigators

• Sponsor: Novartis Vaccines
• Collaborators: GlaxoSmithKline
• Investigators: Study Chair: Novartis Vaccines, Novartis

Publications and helpful links

General Publications

• Leroux-Roels G, Maes C, Willekens J, De Boever F, de Rooij R, Martell L, Bedell L, Wittke F, Slobod K, Dull P. A randomized, observer-blind Phase Ib study to identify formulations and vaccine schedules of a trivalent Group B Streptococcus vaccine for use in non-pregnant and pregnant women. Vaccine. 2016 Apr 4;34(15):1786-91. doi: 10.1016/j.vaccine.2016.02.044. Epub 2016 Mar 5.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: March 31, 2010
• First Submitted That Met QC Criteria: June 23, 2010
• First Posted (Estimate): June 24, 2010

Study Record Updates

• Last Update Posted (Actual): May 15, 2017
• Last Update Submitted That Met QC Criteria: May 8, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Vaccine; Group B streptococcus; GBS; Group B streptococcus (GBS) disease
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: V98_06