Safety and Immunogenicity of a Trivalent Group B Streptococcus Vaccine in Healthy Pregnant Women

NCT02046148 | Completed Phase 2 Results DMC

• 2 other identifiers: 205235V98_12
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 6

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.

Conditions

GBS Disease; Streptococcus Agalactiae

Keywords

Maternal vaccine; IgG; IgA; GBS; pregnant women

Outcome Measures

Primary Outcomes (9)

• Concentration of Serotype Ia GBS IgG Levels in Infant Serum at Delivery and at Days 42 and 90 of Age

  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).

  At Birth, Day 42 and Day 90

• Concentration of Serotype Ib GBS IgG Levels in Infant Serum at Delivery and at Days 42 and 90 of Age

  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

  At Birth, Day 42 and Day 90

• Concentration of Serotype III GBS IgG Levels in Infant Serum at Delivery and at Days 42 and 90 of Age

  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.

  At Birth, Day 42 and Day 90

• 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

  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).

  At Day 1 (pre-vaccination), Day 31 (post-vaccination), Delivery, Days 42 and 90 (postpartum)

• 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

  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.

  At Day 1 (pre-vaccination), Day 31 (post-vaccination), Delivery, Days 42 and 90 (postpartum)

• 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

  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.

  At Day 1 (pre-vaccination), Day 31 (post-vaccination), Delivery, Days 42 and 90 (postpartum)

• 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

  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).

  At Day 31 (post-vaccination), Delivery, Days 42 and 90 (postpartum)

• 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

  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.

  At Day 31 (post-vaccination), Delivery, Days 42 and 90 (postpartum)

• 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

  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.

  At Day 31 (post-vaccination), Delivery, Days 42 and 90 (postpartum)

Secondary Outcomes (19)

• 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

• 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 Solicited Local and Solicited Systemic AEs - Study Days 1-3

  During Study Days 1-3 (from 6 hours through Day 3 post-vaccination)

Study Arms (2)

GBS Group

EXPERIMENTAL

Healthy pregnant women, between and including 18-40 years of age, at 24 0/7 through 34 6/7 weeks of gestation, with the intent to breastfeed, who received a single dose of Group B Streptococcus (GBS) trivalent vaccine, injected intramuscularly. (Pregnant women are referred to as maternal subjects as the study period spans from pregnancy to Day 180 postpartum).

Biological: GBS trivalent vaccine

Placebo Group

ACTIVE COMPARATOR

Healthy pregnant women, between and including 18-40 years of age, at 24 0/7 through 34 6/7 weeks of gestation, with the intent to breastfeed, who received a single dose of Placebo, injected intramuscularly. (Pregnant women are referred to as maternal subjects as the study period spans from pregnancy to Day 180 postpartum).

Biological: Placebo

Interventions

GBS trivalent vaccine BIOLOGICAL

Intramuscular injection - Liquid formulation of a vaccine containing polysaccharide capsules from serotypes Ia, Ib, and III of the Group B Streptococcus and conjugated to the Corynebacterium diphtheriae CRM197 carrier protein

GBS Group

Placebo BIOLOGICAL

Intramuscular injection - Normal saline

Placebo Group

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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 1.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Novartis Vaccines: collaborator

Study Sites (6)

GSK Investigational Site

Aurora, Colorado, 80045, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21201, United States

Location

GSK Investigational Site

Durham, North Carolina, 27705, United States

Location

GSK Investigational Site

Pittsburgh, Pennsylvania, 15213, United States

Location

GSK Investigational Site

Charleston, South Carolina, 29425, United States

Location

GSK Investigational Site

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• 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.

  PMID: 32883555 DERIVED

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2014
• First Posted: January 27, 2014
• Study Start: March 18, 2014
• Primary Completion: December 30, 2015
• Study Completion: March 26, 2016
• Last Updated: December 29, 2020
• Results First Posted: May 30, 2017

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

US (6)