Clinical trial NCT01446289: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Streptococcal Infection
Gram-positive Bacterial Infection
Bacterial Infection
Keywords: Group B streptococcus
GBS
Vaccine
Prevention of group B streptococcus infection
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: Novartis Vaccines
First posted: 2011-10-05
Enrollment: 86
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Geometric Mean Concentrations (GMCs) of Antibodies in Mothers and Infants at Delivery/Birth
timeFrame: Day of delivery/birth
measure: Geometric Mean of the Ratios Between Infant Antibody Level (μg/mL) and Maternal Antibody Level (μg/mL) at Time of Delivery
timeFrame: Day of delivery/birth
Secondary outcomes:
measure: GMCs (Enzyme-linked Immunosorbent Assay, ELISA) Antibodies Against Serotypes Ia, Ib and III in Maternal Subjects
timeFrame: Day 1, day 31 and day 91 post-delivery
measure: Geometric Mean Ratios (GMRs) of Antibody GMCs (ELISA) in Maternal Subjects
timeFrame: Day 31, day of delivery, day 91 post-delivery
measure: GMC (ELISA) of Anti-GBS CPS Antibodies in Infants
timeFrame: Day of birth and day 91 after birth
measure: GMRs of Anti-GBS CPS Antibody GMCs (ELISA) in Infants at 3 Months of Age Versus GMCs at Birth
timeFrame: Day 91 after birth
measure: Percentages of Infant Subjects Showing Anti-diphtheria Antibodies GMCs (ELISA) Over 0.1 IU/mL at 1 Month After the Last Routine Infant Immunization
timeFrame: 1 month after the last routine infant immunization
measure: Percentage of Maternal Subjects Reporting Solicited Local and Systemic Adverse Events (AEs)
timeFrame: From day 1 to 7 after vaccination
measure: Percentage of Maternal Subjects Reporting Unsolicited AEs and Serious Adverse Events (SAEs)
timeFrame: 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.
measure: Percentages of Infants Reporting SAEs
timeFrame: From birth until study termination
Other outcomes:
Locations:
city: Herestraat
country: Belgium
facility: UZ Leuven
state: Leuven
city: Gasthuismolenstraat 31
country: Belgium
facility: Regionaal Ziekenhuis Heilig Hart,
state: Tienen
city: Vancouver
country: Canada
facility: University of British Columbia, Rm B3 25 B, 4500 Oak Street,
state: British Columbia
city: Halifax
country: Canada
facility: Dalhousie University, IWK Health Centre, 5850/5980 University Avenue,
state: Nova Scotia
city: Boulevard laurier, S-745
country: Canada
facility: Centre hospitalier universitaire de Quebec (CHUQ)- hospital CHUL, Centre de recherche en infectiologie, 2705,
state: Quebec
Study officials:
affiliation: Novartis Vaccines
name: Novartis Vaccines
role: STUDY_CHAIR
affiliation: Regional Hospital Heilig Hart, Tienen, Belgium
name: Gilbert Donders, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.