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

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

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.

Study Overview

• Status: Completed
• Conditions: Streptococcal Infections
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 380
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• South Africa
  • Johannesburg
    • Chris Hani Rd, Soweto, Johannesburg, South Africa
      • Chris Hani Baragwanath Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Vaccines
• Investigators: Study Chair: Novartis Vaccines and Diagnostics, Novartis

Publications and helpful links

General Publications

• Cutland CL, Cunnington M, Olugbosi M, Jones SA, Hugo A, Maharaj K, Slobod K, Madhi SA. Lessons learnt from enrolment and follow up of pregnant women and their infants in clinical trials in South Africa, a low-middle income country. Vaccine. 2015 Nov 25;33(47):6406-12. doi: 10.1016/j.vaccine.2015.08.040. Epub 2015 Sep 26.
• Madhi SA, Koen A, Cutland CL, Jose L, Govender N, Wittke F, Olugbosi M, Sobanjo-Ter Meulen A, Baker S, Dull PM, Narasimhan V, Slobod K. Antibody Kinetics and Response to Routine Vaccinations in Infants Born to Women Who Received an Investigational Trivalent Group B Streptococcus Polysaccharide CRM197-Conjugate Vaccine During Pregnancy. Clin Infect Dis. 2017 Nov 13;65(11):1897-1904. doi: 10.1093/cid/cix666.
• Madhi SA, Cutland CL, Jose L, Koen A, Govender N, Wittke F, Olugbosi M, Meulen AS, Baker S, Dull PM, Narasimhan V, Slobod K. Safety and immunogenicity of an investigational maternal trivalent group B streptococcus vaccine in healthy women and their infants: a randomised phase 1b/2 trial. Lancet Infect Dis. 2016 Aug;16(8):923-34. doi: 10.1016/S1473-3099(16)00152-3. Epub 2016 Apr 29.

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: September 1, 2010
• First Submitted That Met QC Criteria: September 1, 2010
• First Posted (Estimate): September 2, 2010

Study Record Updates

• Last Update Posted (Estimate): August 22, 2014
• Last Update Submitted That Met QC Criteria: August 18, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: Vaccine; Group B streptococcus; GBS; Prevention of group B streptococcus infection
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Streptococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines; Pharmaceutical Solutions
• Other Study ID Numbers: V98_08; MCC Reference n° 20100601 (Other Identifier: South African authorities)