A Phase II, Multicenter, Randomized, Observer-Blind, Controlled Study to Evaluate Safety and Immunogenicity of a Trivalent Group B Streptococcus Vaccine in Healthy Pregnant Women
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- GlaxoSmithKline
- Enrollment
- 75
- Locations
- 7
- Primary Endpoint
- Concentration of Serotype Ib GBS IgG Levels in Infant Serum at Delivery and at Days 42 and 90 of Age
Study Overview
Brief Summary
Evaluate the safety and immunogenicity of the trivalent group B streptococcus vaccine in healthy pregnant women. The study will also evaluate the levels of GBS serotype-specific antibodies in infants, placental transfer from the pregnant women to the infant and levels of antibodies in the breast milk.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 40 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Healthy pregnant women 18-40 years of age, inclusive and at 24 0/7 through 34 6/7 weeks gestation.
- •Individuals who intend to breastfeed for at least 90 days postpartum.
- •Individuals who have given 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 can comprehend and comply with all study procedures and are available for follow-up.
Exclusion Criteria
- •Individuals with history of illness or an ongoing illness that, in the opinion of the investigator, may pose additional risk to the subject if she participates in the study.
- •Individuals with known hypersensitivity to any component of the vaccine.
- •Individuals who received or plan to receive any licensed vaccine within 14 days before or after the study vaccine with the exception of inactivated influenza vaccine which may be administered up to 7 days before or after study vaccine.
- •Individuals with an infection requiring systemic antibiotic or antiviral treatment within 7 days prior to Study Day
- •Individuals determined as high risk for serious obstetrical complication, including:
- •Gestational hypertension, as defined by American College of Obstetricians and Gynecologists guidelines (ACOG Practice Bulletin 2012)
- •Gestational diabetes which is not controlled by diet and exercise as per American College of Obstetricians and Gynecologists guidelines (ACOG Practice Bulletin 2013)
- •Pre-eclampsia or eclampsia as defined by American College of Obstetricians and Gynecologists guidelines (ACOG practice bulletin, 2002)
- •HIV infection
- •Obesity class II or greater (pre-pregnancy BMI≥35.0)
- •multiple pregnancy
- •Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the subject's ability to participate in the study.
- •Individuals who are not able to comprehend and to follow all required study procedures for the whole period of the study.
- •Individuals with known or suspected impairment of the immune system including known or suspected HIV infection or HIV-related disease, a history of or an active autoimmune disorder and receipt of immunosuppressive therapy.
- •Long term use of glucocorticoids, including oral or parenteral prednisone ≥ 20 mg/day or equivalent for more than 2 consecutive weeks (or 2 weeks total) within 30 days prior to enrollment. Use of inhaled, intranasal, or topical corticosteroids is allowed.
- •Individuals participating in any clinical trial with another investigational product during the pregnancy or intent to participate in another clinical study at any time during the conduct of this study.
- •Pregnant with a fetus with a known or suspected congenital anomaly
- •Individuals who are acting as study personnel or immediate family members (brother, sister, child, parent) or the spouse of study personnel.
- •Individuals with a fever (oral temperature ≥ 38°C/100.4 °F) within 3 days prior to intended study vaccination.
- •Individuals with a history of culture confirmed GBS case in the infant(s) previously born to her.
Outcomes
Primary Outcomes
Concentration of Serotype Ib GBS IgG Levels in Infant Serum at Delivery and at Days 42 and 90 of Age
Time Frame: At Birth, Day 42 and Day 90
To evaluate serotype-specific Ib GBS serum IgG antibody levels (anti-Ib) in infants born to maternal subjects receiving the GBS trivalent vaccine, as measured at birth, Day 42 and Day 90 of age. As the singleton ELISA was no longer in use at the time of serotypes Ib and III testing, results for both serotypes were tested using multiplex immunoassay
Concentration of Serotype Ia GBS IgG Levels in Infant Serum at Delivery and at Days 42 and 90 of Age
Time Frame: At Birth, Day 42 and Day 90
To evaluate serotype-specific Ia GBS serum IgG antibody levels (anti-Ia) in infants born to maternal subjects receiving the GBS trivalent vaccine, as measured at birth, Day 42 and Day 90 of age. Antibody concentrations were measured by Enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL).
Concentration of Serotype Ib GBS IgG Levels in Maternal Serum at Pre-vaccination, at Study Day 31, at Delivery and at Days 42 and 90 Postpartum
Time Frame: At Day 1 (pre-vaccination), Day 31 (post-vaccination), Delivery, Days 42 and 90 (postpartum)
To evaluate serotype-specific (Ib) GBS serum IgG antibody levels (anti-Ib) in maternal subjects. As the singleton ELISA was no longer in use at the time of serotypes Ib and III testing, results for both serotypes were tested using multiplex immunoassay.
Ratio Relative to Pre-vaccination Levels of Maternal Serum GBS IgG Antibody Levels - Serotype Ia, as Measured at Study Day 31, at Delivery and at Days 42 and 90 Postpartum
Time Frame: At Day 31 (post-vaccination), Delivery, Days 42 and 90 (postpartum)
Geometric Mean Ratio relative to pre-vaccination (Day 1) of serotype-specific (Ia) GBS serum IgG antibody concentrations (anti-Ia) in maternal subjects. Antibody concentrations were measured by Enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL).
Ratio Relative to Pre-vaccination Levels of Maternal Serum GBS IgG Antibody Levels - Serotype Ib, as Measured at Study Day 31, at Delivery and at Days 42 and 90 Postpartum
Time Frame: At Day 31 (post-vaccination), Delivery, Days 42 and 90 (postpartum)
Geometric Mean Ratio relative to pre-vaccination (Day 1) of serotype-specific (Ib) GBS serum IgG antibody concentrations (anti-Ib) in maternal subjects. As the singleton ELISA was no longer in use at the time of serotypes Ib and III testing, results for both serotypes were tested using multiplex immunoassay.
Concentration of Serotype Ia GBS IgG Levels in Maternal Serum at Pre-vaccination, at Study Day 31, at Delivery and at Days 42 and 90 Postpartum
Time Frame: At Day 1 (pre-vaccination), Day 31 (post-vaccination), Delivery, Days 42 and 90 (postpartum)
To evaluate serotype-specific (Ia) GBS serum IgG antibody levels (anti-Ia) in maternal subjects. Antibody concentrations were measured by Enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL).
Concentration of Serotype III GBS IgG Levels in Maternal Serum at Pre-vaccination, at Study Day 31, at Delivery and at Days 42 and 90 Postpartum
Time Frame: At Day 1 (pre-vaccination), Day 31 (post-vaccination), Delivery, Days 42 and 90 (postpartum)
To evaluate serotype-specific (III) GBS serum IgG antibody levels (anti-III) in maternal subjects. As the singleton ELISA was no longer in use at the time of serotypes Ib and III testing, results for both serotypes were tested using multiplex immunoassay.
Ratio Relative to Pre-vaccination Levels of Maternal Serum GBS IgG Antibody Levels - Serotype III, as Measured at Study Day 31, at Delivery and at Days 42 and 90 Postpartum
Time Frame: At Day 31 (post-vaccination), Delivery, Days 42 and 90 (postpartum)
Geometric Mean Ratio relative to pre-vaccination (Day 1) of serotype-specific (III) GBS serum IgG antibody concentrations (anti-III) in maternal subjects. As the singleton ELISA was no longer in use at the time of serotypes Ib and III testing, results for both serotypes were tested using multiplex immunoassay.
Concentration of Serotype III GBS IgG Levels in Infant Serum at Delivery and at Days 42 and 90 of Age
Time Frame: At Birth, Day 42 and Day 90
To evaluate serotype-specific III GBS serum IgG antibody levels (anti-III) in infants born to maternal subjects receiving the GBS trivalent vaccine, as measured at birth, Day 42 and Day 90 of age. As the singleton ELISA was no longer in use at the time of serotypes Ib and III testing, results for both serotypes were tested using multiplex immunoassay.
Secondary Outcomes
- Birth Length and Head Circumference of Infants (Median - Minimum and Maximum)(At birth)
- Ratio of GBS IgG Antibody Levels - Serotype III in Infant Serum Relative to Maternal Serum at the Time of Delivery(At Delivery)
- Percentage of Maternal Subjects With Solicited Local and Solicited Systemic Adverse Events (AEs) up to 30 Minutes(Up to 30 minutes post-vaccination)
- Percentage of Maternal Subjects With Serious Adverse Events (SAEs), Unsolicited Medically Attended AEs (MAEs) and Unsolicited AEs Leading to Study Withdrawal (AEs Lead. Wthwal)(From Study Day 1 through Study Day 31)
- Birth Weight of Infants (Median, Minimum and Maximum)(At Birth)
- Percentage of Maternal Subjects With Any Unsolicited AEs(From Study Day 1 through Study Day 31)
- Percentage of Maternal Subjects With SAEs, Unsolicited MAEs and Unsolicited AEs Leading to Study Withdrawal (AEs Lead. Wthwal)(From Study Day 32 through Day 180 postpartum)
- Percentage of Infants With SAEs, Unsolicited MAEs and AEs Leading to Study Withdrawal(From Birth through Day 180 of age)
- Birth Length and Head Circumference of Infants (Mean - Standard Deviation)(At Birth)
- Ratio of GBS IgG Antibody Levels - Serotype Ia in Infant Serum Relative to Maternal Serum at the Time of Delivery(At Delivery)
- Ratio of GBS IgG Antibody Levels - Serotype Ib in Infant Serum Relative to Maternal Serum at the Time of Delivery(At Delivery)
- Percentage of Maternal Subjects With Solicited Local and Solicited Systemic AEs - Study Days 4-7(During Study Days 4-7)
- Percentage of Maternal Subjects With Solicited Local and Solicited Systemic AEs - Study Days 1-7(During Study Days 1-7 (from 6 hours through Day 7 post-vaccination))
- Birth Weight of Infants (Mean-Standard Deviation)(At Birth)
- Percentage of Maternal Subjects With Solicited Local and Solicited Systemic AEs - Study Days 1-3(During Study Days 1-3 (from 6 hours through Day 3 post-vaccination))
- Infants Apgar Scores (Mean - Standard Deviation)(At 1, 5 and 10 minutes)
- Descriptive Statistics for the Score for the Long-term Developmental Outcome Assessed by Bayley Scales of Infant and Toddler Development 3rd Edition Screening Test (PsychCorp) in Infants (Mean - Standard Deviation)(At Day 180 of age)
- Infants Apgar Scores (Median, Minimum and Maximum)(At 1, 5 and 10 minutes)
- Descriptive Statistics for the Score for the Long-term Developmental Outcome Assessed by Bayley Scales of Infant and Toddler Development 3rd Edition Screening Test (PsychCorp) in Infants (Median, Minimum and Maximum)(At Day 180 of age)