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Immune Response Induced by a Vaccine Against Group B Streptococcus and Safety in Pregnant Women and Their Offsprings

Primary Purpose

Streptococcal Infection, Gram-positive Bacterial Infection, Bacterial Infection

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Group B Streptococcus Trivalent Vaccine
Placebo
Sponsored by
Novartis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Streptococcal Infection focused on measuring Group B streptococcus, GBS, Vaccine, Prevention of group B streptococcus infection

Eligibility Criteria

18 Years - 40 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  1. Healthy pregnant women 18-40 years of age at 24-35 weeks of gestation at screening.
  2. Individuals who have given a written consent after the nature of the study has been explained according to local regulatory requirements.
  3. Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator.
  4. Individuals who will be available for all scheduled visits (ie, not planning to leave the area before the end of the study period).

Exclusion Criteria:

  1. Individuals who were unwilling and/or unable to give written informed consent to participate in the study.
  2. Individuals with a history of severe allergic reactions after previous vaccinations such as anaphylactic shock, asthma, urticaria, or other allergic reaction or hypersensitivity to any vaccine component.
  3. Individuals with any known or suspected impairment/alteration of immune function, either congenital or acquired or resulting from:

    • receipt of immunosuppressive therapy within 30 days prior to enrollment (any systemic corticosteroid administered for more than 5 days, or in a daily dose > 15 mg/kg/day prednisone or equivalent during any of 30 days prior to enrollment, or cancer chemotherapy).
    • receipt of immunostimulants.
    • receipt of parenteral immunoglobulin preparation, blood products, and /or plasma derivatives within 12 weeks prior to enrollment and for the full length of the study.

    Note: Anti-D (Rho) Immunoglobulins (anti-RhD) given for Anti-D prophylaxis were to be allowed.

  4. Individuals characterized as "high risk" pregnancies at investigator discretion, such as those who have:

    • gestational diabetes
    • preeclampsia/eclampsia
    • women at risk of preterm labor (except positivity for vaginal GBS)
    • History of previous pregnancy complications including delivery of preterm infant.
    • History of still-birth, late abortions and children with congenital anomalies.
  5. Individuals who had received any other investigational agent or investigational intervention during the course of the study.
  6. Individuals with acute infection including oral temperature ≥ 38°C were to be temporarily excluded. They could be enrolled once the infection had resolved (as judged by investigator).
  7. HIV positive by history.
  8. Individuals reporting any known or suspected serious acute, chronic or progressive disease (eg, any history of neoplasm, malignancy, including lymphoproliferative disorder, diabetes, cardiac disease, malnutrition, renal failure, autoimmune disease, HBV or HCV, blood disorders).

    Note: Malignancies, highly likely to having been cured at the investigators discretion are allowed. (eg, no relapse since 5 years post last malignancy specific treatment).

  9. Individuals with bleeding diathesis, or any condition that might have been associated with a prolonged bleeding time.
  10. Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, might have interfered with the subject's ability to participate in the study (eg, who were not able to comprehend or to follow all required study procedures for the whole period of the study).
  11. Individuals with any progressive or severe neurologic disorder, seizure disorder, epilepsy or Guillain-Barré syndrome.
  12. Individuals with history or any illness that, in the opinion of the investigator, might have posed additional risk to subjects due to participation in the study.
  13. Individuals who were part of study personnel or close family members conducting this study.

Sites / Locations

  • UZ Leuven
  • Regionaal Ziekenhuis Heilig Hart,
  • University of British Columbia, Rm B3 25 B, 4500 Oak Street,
  • Dalhousie University, IWK Health Centre, 5850/5980 University Avenue,
  • Centre hospitalier universitaire de Quebec (CHUQ)- hospital CHUL, Centre de recherche en infectiologie, 2705,

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Group B Streptococcus Trivalent Vaccine

Placebo

Arm Description

Pregnant women who received one injection of Group B Streptococcus Trivalent Vaccine.

Pregnant women who received one injection of saline solution.

Outcomes

Primary Outcome Measures

Geometric Mean Concentrations (GMCs) of Antibodies in Mothers and Infants at Delivery/Birth
GMCs of anti-Group B Streptococcus (GBS) capsular polysaccharide (CPS) antibodies against serotypes Ia, Ib and III in mothers and in infants at delivery/birth are presented.
Geometric Mean of the Ratios Between Infant Antibody Level (μg/mL) and Maternal Antibody Level (μg/mL) at Time of Delivery
The Geometric mean transfer ratio of anti-GBS CPS antibodies 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.

Secondary Outcome Measures

GMCs (Enzyme-linked Immunosorbent Assay, ELISA) Antibodies Against Serotypes Ia, Ib and III in Maternal Subjects
GMCs (ELISA) of anti-GBS CPS antibodies against serotypes Ia, Ib and III in maternal subjects at study day 1, study day 31 and at day 91 post-partum after one administration of GBS vaccine or placebo are reported.
Geometric Mean Ratios (GMRs) of Antibody GMCs (ELISA) in Maternal Subjects
GMRs of GMCs (ELISA) of anti-GBS CPS antibodies against serotypes Ia, Ib and III, in maternal subjects at study day 31, at delivery and at day 91 post-partum versus day 1 (baseline) after one administration of GBS vaccine or placebo are reported.
GMC (ELISA) of Anti-GBS CPS Antibodies in Infants
GMC (ELISA) of anti-GBS CPS antibodies against serotypes Ia, Ib and III in infants at birth and at 3 months of age are reported.
GMRs of Anti-GBS CPS Antibody GMCs (ELISA) in Infants at 3 Months of Age Versus GMCs at Birth
GMRs of anti-GBS CPS antibody GMCs (ELISA) against serotypes Ia, Ib and III in infants at 3 months of age (day 91 after birth) versus GMCs at birth are reported.
Percentages of Infant Subjects Showing Anti-diphtheria Antibodies GMCs (ELISA) Over 0.1 IU/mL at 1 Month After the Last Routine Infant Immunization
Percentages of infant subjects showing anti-diphtheria antibodies GMCs (ELISA) over 0.1 IU/mL in sera collected at 1 month after the last routine infant immunization (ie, either 5 months or 7 months after birth, depending on the vaccination schedule) are reported.
Percentage of Maternal Subjects Reporting Solicited Local and Systemic Adverse Events (AEs)
Percentage of maternal subjects reporting solicited local and systemic AEs and other indicators of reactogenicity from day 1 to 7 after vaccination are reported.
Percentage of Maternal Subjects Reporting Unsolicited AEs and Serious Adverse Events (SAEs)
Percentage of maternal subjects reporting unsolicited AEs, SAEs, AEs requiring a non-routine physician's visit, AEs leading to withdrawal are reported.
Percentages of Infants Reporting SAEs
Percentages of infants born from women who received either one injection of the study vaccine or placebo, reporting SAEs from birth until study termination are reported.

Full Information

First Posted
September 27, 2011
Last Updated
September 5, 2014
Sponsor
Novartis
Collaborators
Novartis Vaccines
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1. Study Identification

Unique Protocol Identification Number
NCT01446289
Brief Title
Immune Response Induced by a Vaccine Against Group B Streptococcus and Safety in Pregnant Women and Their Offsprings
Official Title
A Phase II Randomized, Observer-Blind, Multi-Center, Controlled Study of a Trivalent Group B Streptococcus Vaccine in Healthy Pregnant Women
Study Type
Interventional

2. Study Status

Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
September 2011 (undefined)
Primary Completion Date
April 2013 (Actual)
Study Completion Date
October 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis
Collaborators
Novartis Vaccines

4. Oversight

5. Study Description

Brief Summary
The study investigated the immune response induced by the Group B streptococcus vaccine in healthy pregnant women. In addition, the study investigated the amount of vaccine induced antibodies which were transferred to the newborn.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Streptococcal Infection, Gram-positive Bacterial Infection, Bacterial Infection
Keywords
Group B streptococcus, GBS, Vaccine, Prevention of group B streptococcus infection

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
86 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group B Streptococcus Trivalent Vaccine
Arm Type
Experimental
Arm Description
Pregnant women who received one injection of Group B Streptococcus Trivalent Vaccine.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Pregnant women who received one injection of saline solution.
Intervention Type
Biological
Intervention Name(s)
Group B Streptococcus Trivalent Vaccine
Intervention Description
Pregnant women who received one injection of Group B Streptococcus Trivalent Vaccine administered intramuscularly.
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Pregnant women who received one injection of saline solution administered intramuscularly.
Primary Outcome Measure Information:
Title
Geometric Mean Concentrations (GMCs) of Antibodies in Mothers and Infants at Delivery/Birth
Description
GMCs of anti-Group B Streptococcus (GBS) capsular polysaccharide (CPS) antibodies against serotypes Ia, Ib and III in mothers and in infants at delivery/birth are presented.
Time Frame
Day of delivery/birth
Title
Geometric Mean of the Ratios Between Infant Antibody Level (μg/mL) and Maternal Antibody Level (μg/mL) at Time of Delivery
Description
The Geometric mean transfer ratio of anti-GBS CPS antibodies 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.
Time Frame
Day of delivery/birth
Secondary Outcome Measure Information:
Title
GMCs (Enzyme-linked Immunosorbent Assay, ELISA) Antibodies Against Serotypes Ia, Ib and III in Maternal Subjects
Description
GMCs (ELISA) of anti-GBS CPS antibodies against serotypes Ia, Ib and III in maternal subjects at study day 1, study day 31 and at day 91 post-partum after one administration of GBS vaccine or placebo are reported.
Time Frame
Day 1, day 31 and day 91 post-delivery
Title
Geometric Mean Ratios (GMRs) of Antibody GMCs (ELISA) in Maternal Subjects
Description
GMRs of GMCs (ELISA) of anti-GBS CPS antibodies against serotypes Ia, Ib and III, in maternal subjects at study day 31, at delivery and at day 91 post-partum versus day 1 (baseline) after one administration of GBS vaccine or placebo are reported.
Time Frame
Day 31, day of delivery, day 91 post-delivery
Title
GMC (ELISA) of Anti-GBS CPS Antibodies in Infants
Description
GMC (ELISA) of anti-GBS CPS antibodies against serotypes Ia, Ib and III in infants at birth and at 3 months of age are reported.
Time Frame
Day of birth and day 91 after birth
Title
GMRs of Anti-GBS CPS Antibody GMCs (ELISA) in Infants at 3 Months of Age Versus GMCs at Birth
Description
GMRs of anti-GBS CPS antibody GMCs (ELISA) against serotypes Ia, Ib and III in infants at 3 months of age (day 91 after birth) versus GMCs at birth are reported.
Time Frame
Day 91 after birth
Title
Percentages of Infant Subjects Showing Anti-diphtheria Antibodies GMCs (ELISA) Over 0.1 IU/mL at 1 Month After the Last Routine Infant Immunization
Description
Percentages of infant subjects showing anti-diphtheria antibodies GMCs (ELISA) over 0.1 IU/mL in sera collected at 1 month after the last routine infant immunization (ie, either 5 months or 7 months after birth, depending on the vaccination schedule) are reported.
Time Frame
1 month after the last routine infant immunization
Title
Percentage of Maternal Subjects Reporting Solicited Local and Systemic Adverse Events (AEs)
Description
Percentage of maternal subjects reporting solicited local and systemic AEs and other indicators of reactogenicity from day 1 to 7 after vaccination are reported.
Time Frame
From day 1 to 7 after vaccination
Title
Percentage of Maternal Subjects Reporting Unsolicited AEs and Serious Adverse Events (SAEs)
Description
Percentage of maternal subjects reporting unsolicited AEs, SAEs, AEs requiring a non-routine physician's visit, AEs leading to withdrawal are reported.
Time Frame
All AEs were recorded until delivery, after delivery all AEs requiring a non-routine physician's visit and AEs leading to withdrawal from the study. SAEs were collected for the duration of the trial.
Title
Percentages of Infants Reporting SAEs
Description
Percentages of infants born from women who received either one injection of the study vaccine or placebo, reporting SAEs from birth until study termination are reported.
Time Frame
From birth until study termination

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy pregnant women 18-40 years of age at 24-35 weeks of gestation at screening. Individuals who have given a written consent after the nature of the study has been explained according to local regulatory requirements. Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator. Individuals who will be available for all scheduled visits (ie, not planning to leave the area before the end of the study period). Exclusion Criteria: Individuals who were unwilling and/or unable to give written informed consent to participate in the study. Individuals with a history of severe allergic reactions after previous vaccinations such as anaphylactic shock, asthma, urticaria, or other allergic reaction or hypersensitivity to any vaccine component. Individuals with any known or suspected impairment/alteration of immune function, either congenital or acquired or resulting from: receipt of immunosuppressive therapy within 30 days prior to enrollment (any systemic corticosteroid administered for more than 5 days, or in a daily dose > 15 mg/kg/day prednisone or equivalent during any of 30 days prior to enrollment, or cancer chemotherapy). receipt of immunostimulants. receipt of parenteral immunoglobulin preparation, blood products, and /or plasma derivatives within 12 weeks prior to enrollment and for the full length of the study. Note: Anti-D (Rho) Immunoglobulins (anti-RhD) given for Anti-D prophylaxis were to be allowed. Individuals characterized as "high risk" pregnancies at investigator discretion, such as those who have: gestational diabetes preeclampsia/eclampsia women at risk of preterm labor (except positivity for vaginal GBS) History of previous pregnancy complications including delivery of preterm infant. History of still-birth, late abortions and children with congenital anomalies. Individuals who had received any other investigational agent or investigational intervention during the course of the study. Individuals with acute infection including oral temperature ≥ 38°C were to be temporarily excluded. They could be enrolled once the infection had resolved (as judged by investigator). HIV positive by history. Individuals reporting any known or suspected serious acute, chronic or progressive disease (eg, any history of neoplasm, malignancy, including lymphoproliferative disorder, diabetes, cardiac disease, malnutrition, renal failure, autoimmune disease, HBV or HCV, blood disorders). Note: Malignancies, highly likely to having been cured at the investigators discretion are allowed. (eg, no relapse since 5 years post last malignancy specific treatment). Individuals with bleeding diathesis, or any condition that might have been associated with a prolonged bleeding time. Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, might have interfered with the subject's ability to participate in the study (eg, who were not able to comprehend or to follow all required study procedures for the whole period of the study). Individuals with any progressive or severe neurologic disorder, seizure disorder, epilepsy or Guillain-Barré syndrome. Individuals with history or any illness that, in the opinion of the investigator, might have posed additional risk to subjects due to participation in the study. Individuals who were part of study personnel or close family members conducting this study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Vaccines
Organizational Affiliation
Novartis Vaccines
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Gilbert Donders, Prof.
Organizational Affiliation
Regional Hospital Heilig Hart, Tienen, Belgium
Official's Role
Principal Investigator
Facility Information:
Facility Name
UZ Leuven
City
Herestraat
State/Province
Leuven
ZIP/Postal Code
49-B-3000
Country
Belgium
Facility Name
Regionaal Ziekenhuis Heilig Hart,
City
Gasthuismolenstraat 31
State/Province
Tienen
ZIP/Postal Code
3300
Country
Belgium
Facility Name
University of British Columbia, Rm B3 25 B, 4500 Oak Street,
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6H3N1
Country
Canada
Facility Name
Dalhousie University, IWK Health Centre, 5850/5980 University Avenue,
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3K 6R8
Country
Canada
Facility Name
Centre hospitalier universitaire de Quebec (CHUQ)- hospital CHUL, Centre de recherche en infectiologie, 2705,
City
Boulevard laurier, S-745
State/Province
Quebec
ZIP/Postal Code
G1V 4G2
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
29374589
Citation
Fabbrini M, Rigat F, Tuscano G, Chiarot E, Donders G, Devlieger R, Filippini S, Frigimelica E, Forte P, Wittke F, Halperin SA, Slobod K, Grandi G, Margarit I. Functional activity of maternal and cord antibodies elicited by an investigational group B Streptococcus trivalent glycoconjugate vaccine in pregnant women. J Infect. 2018 May;76(5):449-456. doi: 10.1016/j.jinf.2018.01.006. Epub 2018 Jan 31.
Results Reference
derived
PubMed Identifier
26942345
Citation
Donders GG, Halperin SA, Devlieger R, Baker S, Forte P, Wittke F, Slobod KS, Dull PM. Maternal Immunization With an Investigational Trivalent Group B Streptococcal Vaccine: A Randomized Controlled Trial. Obstet Gynecol. 2016 Feb;127(2):213-21. doi: 10.1097/AOG.0000000000001190.
Results Reference
derived

Learn more about this trial

Immune Response Induced by a Vaccine Against Group B Streptococcus and Safety in Pregnant Women and Their Offsprings

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