Clinical trial NCT02046148: Safety and Immunogenicity of a Trivalent Group B Streptococcus Vaccine in Healthy Pregnant Women
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: GBS Disease
Streptococcus Agalactiae
Keywords: Maternal vaccine
IgG
IgA
GBS
pregnant women
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Novartis Vaccines
First posted: 2014-01-27
Enrollment: 75
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: Inclusion Criteria:

1. Healthy pregnant women 18-40 years of age, inclusive and at 24 0/7 through 34 6/7 weeks gestation.
2. Individuals who intend to breastfeed for at least 90 days postpartum.
3. Individuals who have given written consent after the nature of the study has been explained according to local regulatory requirements.
4. Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator.
5. Individuals who can comprehend and comply with all study procedures and are available for follow-up.

Exclusion Criteria:

1. 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.
2. Individuals with known hypersensitivity to any component of the vaccine.
3. 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.
4. Individuals with an infection requiring systemic antibiotic or antiviral treatment within 7 days prior to Study Day 1.
5. 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
6. 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.
7. Individuals who are not able to comprehend and to follow all required study procedures for the whole period of the study.
8. 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.
9. 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.
10. 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.
11. Pregnant with a fetus with a known or suspected congenital anomaly
12. Individuals who are acting as study personnel or immediate family members (brother, sister, child, parent) or the spouse of study personnel.
13. Individuals with a fever (oral temperature ≥ 38°C/100.4 °F) within 3 days prior to intended study vaccination.
14. Individuals with a history of culture confirmed GBS case in the infant(s) previously born to her.

Primary outcomes:
measure: Concentration of Serotype Ia GBS IgG Levels in Infant Serum at Delivery and at Days 42 and 90 of Age
timeFrame: At Birth, Day 42 and Day 90
measure: Concentration of Serotype Ib GBS IgG Levels in Infant Serum at Delivery and at Days 42 and 90 of Age
timeFrame: At Birth, Day 42 and Day 90
measure: Concentration of Serotype III GBS IgG Levels in Infant Serum at Delivery and at Days 42 and 90 of Age
timeFrame: At Birth, Day 42 and Day 90
measure: 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
timeFrame: At Day 1 (pre-vaccination), Day 31 (post-vaccination), Delivery, Days 42 and 90 (postpartum)
measure: 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
timeFrame: At Day 1 (pre-vaccination), Day 31 (post-vaccination), Delivery, Days 42 and 90 (postpartum)
measure: 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
timeFrame: At Day 1 (pre-vaccination), Day 31 (post-vaccination), Delivery, Days 42 and 90 (postpartum)
measure: 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
timeFrame: At Day 31 (post-vaccination), Delivery, Days 42 and 90 (postpartum)
measure: 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
timeFrame: At Day 31 (post-vaccination), Delivery, Days 42 and 90 (postpartum)
measure: 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
timeFrame: At Day 31 (post-vaccination), Delivery, Days 42 and 90 (postpartum)
Secondary outcomes:
measure: Ratio of GBS IgG Antibody Levels - Serotype Ia in Infant Serum Relative to Maternal Serum at the Time of Delivery
timeFrame: At Delivery
measure: Ratio of GBS IgG Antibody Levels - Serotype Ib in Infant Serum Relative to Maternal Serum at the Time of Delivery
timeFrame: At Delivery
measure: Ratio of GBS IgG Antibody Levels - Serotype III in Infant Serum Relative to Maternal Serum at the Time of Delivery
timeFrame: At Delivery
measure: Percentage of Maternal Subjects With Solicited Local and Solicited Systemic Adverse Events (AEs) up to 30 Minutes
timeFrame: Up to 30 minutes post-vaccination
measure: Percentage of Maternal Subjects With Solicited Local and Solicited Systemic AEs - Study Days 1-3
timeFrame: During Study Days 1-3 (from 6 hours through Day 3 post-vaccination)
measure: Percentage of Maternal Subjects With Solicited Local and Solicited Systemic AEs - Study Days 4-7
timeFrame: During Study Days 4-7
measure: Percentage of Maternal Subjects With Solicited Local and Solicited Systemic AEs - Study Days 1-7
timeFrame: During Study Days 1-7 (from 6 hours through Day 7 post-vaccination)
measure: Percentage of Maternal Subjects With Any Unsolicited AEs
timeFrame: From Study Day 1 through Study Day 31
measure: Percentage of Maternal Subjects With Serious Adverse Events (SAEs), Unsolicited Medically Attended AEs (MAEs) and Unsolicited AEs Leading to Study Withdrawal (AEs Lead. Wthwal)
timeFrame: From Study Day 1 through Study Day 31
measure: Percentage of Maternal Subjects With SAEs, Unsolicited MAEs and Unsolicited AEs Leading to Study Withdrawal (AEs Lead. Wthwal)
timeFrame: From Study Day 32 through Day 180 postpartum
measure: Percentage of Infants With SAEs, Unsolicited MAEs and AEs Leading to Study Withdrawal
timeFrame: From Birth through Day 180 of age
measure: Birth Weight of Infants (Mean-Standard Deviation)
timeFrame: At Birth
measure: Birth Weight of Infants (Median, Minimum and Maximum)
timeFrame: At Birth
measure: Birth Length and Head Circumference of Infants (Mean - Standard Deviation)
timeFrame: At Birth
measure: Birth Length and Head Circumference of Infants (Median - Minimum and Maximum)
timeFrame: At birth
measure: Infants Apgar Scores (Mean - Standard Deviation)
timeFrame: At 1, 5 and 10 minutes
measure: Infants Apgar Scores (Median, Minimum and Maximum)
timeFrame: At 1, 5 and 10 minutes
measure: 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)
timeFrame: At Day 180 of age
measure: 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)
timeFrame: At Day 180 of age
Other outcomes:
Locations:
city: Aurora
country: United States
facility: GSK Investigational Site
state: Colorado
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Durham
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Swamy GK, Metz TD, Edwards KM, Soper DE, Beigi RH, Campbell JD, Grassano L, Buffi G, Dreisbach A, Margarit I, Karsten A, Henry O, Lattanzi M, Bebia Z. Safety and immunogenicity of an investigational maternal trivalent group B streptococcus vaccine in pregnant women and their infants: Results from a randomized placebo-controlled phase II trial. Vaccine. 2020 Oct 14;38(44):6930-6940. doi: 10.1016/j.vaccine.2020.08.056. Epub 2020 Sep 1.