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

Bacterial Infection Clinical Trial

Official title:

A Phase II Randomized, Observer-Blind, Multi-Center, Controlled Study of a Trivalent Group B Streptococcus Vaccine in Healthy Pregnant Women

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01446289
• Other study ID #: V98_04
• Secondary ID: 2010-020840-36
• Status: Completed
• Phase: Phase 2
• First received: September 27, 2011
• Last updated: September 5, 2014
• Start date: September 2011
• Est. completion date: October 2013

Study information

• Verified date: September 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Public Health Agency of Canada - Health CanadaBelgium: FAMHP, Federal Agency for Medicinal and Health Products
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: October 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Bacterial Infection
• Bacterial Infections
• Communicable Diseases
• Gram-positive Bacterial Infection
• Gram-Positive Bacterial Infections
• Infection
• Streptococcal Infection
• Streptococcal Infections

Intervention

Biological:
• Group B Streptococcus Trivalent Vaccine
Pregnant women who received one injection of Group B Streptococcus Trivalent Vaccine administered intramuscularly.
• Placebo
Pregnant women who received one injection of saline solution administered intramuscularly.

Locations

Country	Name	City	State
Belgium	Regionaal Ziekenhuis Heilig Hart,	Gasthuismolenstraat 31	Tienen
Belgium	UZ Leuven	Herestraat	Leuven
Canada	Centre hospitalier universitaire de Quebec (CHUQ)- hospital CHUL, Centre de recherche en infectiologie, 2705,	Boulevard laurier, S-745	Quebec
Canada	Dalhousie University, IWK Health Centre, 5850/5980 University Avenue,	Halifax	Nova Scotia
Canada	University of British Columbia, Rm B3 25 B, 4500 Oak Street,	Vancouver	British Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Novartis	Novartis Vaccines

Countries where clinical trial is conducted

Belgium,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day of delivery/birth	No
Primary	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.	Day of delivery/birth	No
Secondary	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.	Day 1, day 31 and day 91 post-delivery	No
Secondary	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.	Day 31, day of delivery, day 91 post-delivery	No
Secondary	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.	Day of birth and day 91 after birth	No
Secondary	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.	Day 91 after birth	No
Secondary	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.	1 month after the last routine infant immunization	No
Secondary	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.	From day 1 to 7 after vaccination	Yes
Secondary	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.	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.	Yes
Secondary	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.	From birth until study termination	Yes