Magnitude of the Antibody Response to and Safety of a GBS Trivalent Vaccine in HIV Positive and HIV Negative Pregnant Women and Their Offsprings

A Phase II Open-Label, Multi-Center Study of a Group B Streptococcus Vaccine in HIV Positive and HIV Negative Pregnant Women

The study compared the magnitude of the antibody response and safety of a GBS Trivalent Vaccine in HIV positive and HIV negative pregnant women and their offspring. In addition the study investigated the maternal to fetal transfer of antibodies induced by the investigational vaccine.

Study Overview

• Status: Completed
• Conditions: Bacterial Infections; Streptococcal Infections; Gram-Positive Bacterial Infections
• Intervention / Treatment: Biological: Group B streptococcus vaccine

• Study Type: Interventional
• Enrollment (Actual): 270
• Phase: Phase 2

Contacts and Locations

Study Locations

• Malawi
  • Blantyre, Malawi
    • Limbe Health Center
• South Africa
  • Bertsham, South Africa, 2013
    • 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:

• Pregnant women 18-40 years of age between 24-35 weeks gestation
• Women who were HIVneg or HIVpos with WHO stage I or II disease and with CD4+ counts > 50 cells/µL

Exclusion Criteria:

• Women who had CD4+ count ≤ 50 cells/µL
• Women who were HIVpos with WHO stage III or IV disease, history of severe allergic reactions after previous vaccinations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HIVneg; HIV-antibody negative maternal subjects at 24 to 35 weeks gestation received one dose of Group B streptococcus vaccine.	Biological: Group B streptococcus vaccine; Subjects receive one dose of 5 μg of each of the 3 glycoconjugates present in the Group B streptococcus vaccine.
Experimental: HIVposCD4HIGH; HIV-antibody positive maternal subjects at 24 to 35 weeks gestation with CD4+ count >350 cells/µL received one dose of Group B streptococcus vaccine.	Biological: Group B streptococcus vaccine; Subjects receive one dose of 5 μg of each of the 3 glycoconjugates present in the Group B streptococcus vaccine.
Experimental: HIVposCD4LOW; HIV-antibody positive maternal subjects at 24 to 35 weeks gestation with CD4+ count ≤350 cells/µL but > 50 cells/µL received one dose of Group B streptococcus vaccine	Biological: Group B streptococcus vaccine; Subjects receive one dose of 5 μg of each of the 3 glycoconjugates present in the Group B streptococcus vaccine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Concentrations (GMCs) of Antibodies in Maternal Subjects and Infants at Delivery/Birth	GMCs of Group B Streptococcus (GBS)-specific Abs against serotypes Ia, Ib and III in mothers and in infants at delivery/birth are presented.	Day of delivery/birth
Geometric Mean Antibody Transfer Ratio Between Infant Antibody Level (μg/mL) and Maternal Antibody Level (μg/mL), for GBS Serotypes Ia, Ib and III at Delivery/Birth.	The Geometric mean transfer ratio of GBS-specific Ab against serotypes Ia, Ib and III at delivery is calculated as the geometric mean of the pairwise ratios between the antibody concentrations from infant at birth and to maternal serum concentration at delivery.	Day of delivery/birth

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vaccine Induced Maternal Serotype Specific GBS Antibody Levels for GBS Serotypes Ia, Ib and III at Day 1, 15, 31 and at Delivery	Immunogenicity was measured as Geometric Mean Concentration of Antibody levels for GBS Serotypes Ia, Ib and III after receiving one dose of GBS Trivalent Vaccine.	Day 1, 15, 31 and at Delivery
Percentages of Maternal Subjects With The Enzyme-linked Immunosorbent Assay (ELISA) Antibody Levels for GBS Serotypes Ia, Ib and III Above a Specific Threshold at Delivery	Immunogenicity was measured in terms of the percentages of maternal subjects with ELISA Antibody Levels for GBS Serotypes Ia, Ib and III Above a Specific Threshold after receiving one dose of GBS Trivalent Vaccine.Threshold values of 0.1, 0.2, 0.5, 1, 2, 3, 5, and 8 μg/mL were used for serum concentrations for maternal subjects.	Day of Delivery
Percentages of Subjects With Solicited Local Adverse Events (AEs)	Safety was assessed in terms of the number of subjects with solicited local AEs after receiving one dose of the GBS Trivalent Vaccine	From 6 Hours to Day 7 After Each Vaccination, for up to 24 weeks
Percentages of Subjects With Solicited Systemic AEs	Safety was assessed in terms of the number of subjects with solicited systemic AEs after receiving one dose of the GBS Trivalent Vaccine	From 6 Hours to Day 7 After Each Vaccination, for up to 24 weeks
Percentages of Subjects Who Experienced Unsolicited Adverse Events	Safety was assessed in terms of the number of subjects who experienced Unsolicited Adverse Events after receiving one dose of the GBS Trivalent Vaccine	Day 1 to Study Termination, for up to 24 weeks
Percentages of Infants Who Experienced Unsolicited Adverse Events	Safety in Infants was assessed in terms of the number of subjects who experienced Unsolicited Adverse Events since birth to study termination	Birth to Study Termination, for up to 24 weeks

Collaborators and Investigators

• Sponsor: Novartis Vaccines

Publications and helpful links

General Publications

• Heyderman RS, Madhi SA, French N, Cutland C, Ngwira B, Kayambo D, Mboizi R, Koen A, Jose L, Olugbosi M, Wittke F, Slobod K, Dull PM. Group B streptococcus vaccination in pregnant women with or without HIV in Africa: a non-randomised phase 2, open-label, multicentre trial. Lancet Infect Dis. 2016 May;16(5):546-555. doi: 10.1016/S1473-3099(15)00484-3. Epub 2016 Feb 8.

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: August 8, 2011
• First Submitted That Met QC Criteria: August 8, 2011
• First Posted (Estimate): August 9, 2011

Study Record Updates

• Last Update Posted (Estimate): September 12, 2014
• Last Update Submitted That Met QC Criteria: September 5, 2014
• Last Verified: September 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: Pathologic Processes; Disease Attributes; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Bacterial Infections; Streptococcal Infections; Gram-Positive Bacterial Infections
• Other Study ID Numbers: V98_05