To assess the safety and tolerability of IVT GBS-06 vaccine administered as a single-dose regimen, at three dosage levels in healthy, non-pregnant, adult women of childbearing age (WOCBA).
This is a phase I/II, randomized, placebo-controlled, observer-blinded trial to evaluate the safety, tolerability, and immunogenicity of a multivalent GBS vaccine candidate in healthy, non-pregnant, adult WOCBA, 18-49 years of age, at two sites, one each in the US and South Africa. Approximately 600 participants will be randomized to receive a single dose of low, mid, or high concentration of IVT GBS-06, or a placebo (saline control) at Day (D)1, administered IM by injecting 0.5 mL into the deltoid muscle. The three dose levels denote the amount of capsular polysaccharide (CPS) for each of the six serotypes per 0.5 mL. These four study groups will be enrolled simultaneously to allow for parallel assessments of overall IVT GBS-06 safety and tolerability. Participants will be randomized in a 1:1:1:1 ratio to one of the dose levels or placebo. This study will utilize a sentinel-cohort design in which 20 participants overall (i.e., N=5 per treatment arm) at the US site will be randomized, vaccinated, and evaluated for safety prior to opening enrolment of additional participants in USA and in South Africa. This study targets representation from both study populations and therefore at least 220 participants will be recruited from each of the two sites and will allow competitive enrollment across the two study sites for the remaining 160 participants to reach 600 within target enrollment period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
600
Hexavalent Group B Streptococcus polysaccharide conjugate vaccine (serotypes Ia, Ib, II, III, V, and VII) administered as a single dose.
0.9% sodium chloride
NYU Grossman School of Medicine
New York, New York, United States
Wits Vaccines and Infectious Diseases Analytics Research Unit (Wits-VIDA), University of the Witwatersrand
Johannesburg, Gauteng, South Africa
Safety -percentage of participants reporting immediate AE within 30 minutes of vaccination
The percentage of participants reporting immediate AE within 30 minutes of vaccination.
Time frame: 30 minutes after vaccination
Safety - percentage of participants reporting solicited local adverse events (AEs) within 7 days of vaccination
The percentage of participants reporting solicited local adverse events (AEs) within 7 days following study vaccination (pain, redness and swelling/induration at the injection site).
Time frame: Day 1 - Day 7 after vaccination
Safety- percentage of participants reporting solicited systemic AEs within 7 days following study vaccination (fever, fatigue, headache, chills, myalgia, arthralgia, and nausea/vomiting)
The percentage of participants reporting solicited systemic AEs within 7 days following study vaccination (fever, fatigue, headache, chills, myalgia, arthralgia, and nausea/vomiting)
Time frame: Day 1 - Day 7 after vaccination
Safety - percentage of participants reporting unsolicited AEs within 28 days following study vaccination
The percentage of participants reporting unsolicited AEs within 28 days following study vaccination
Time frame: Day 1 - Day 28 after vaccination
Safety - percentage of participants with clinically significant laboratory abnormalities within 7 days following study vaccination
The percentage of participants with clinically significant laboratory abnormalities within 7 days following study vaccination
Time frame: Day 1 - Day 7 after vaccination
Safety - percentage of participants reporting medically attended adverse events (MAAEs)
The percentage of participants reporting medically attended adverse events (MAAEs)
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Time frame: From Day 1 vaccination through the end of study
Safety - percentage of participants reporting serious adverse events (SAEs)
The percentage of participants reporting serious adverse events (SAEs)
Time frame: From Day 1 vaccination through the end of study
Immunogenicity - IgG
Percentage of participants that seroconvert per serotype. Seroconversion is defined as induction of a serotype-specific anti- capsular polysaccharide (anti-CPS) IgG concentration that is at least 4-fold greater than the Multiplex immunoassay (MIA) lower limit of quantitation (LLOQ) or the baseline level, whichever is higher.
Time frame: Day 1 baseline collection through 4-weeks post dose collection
Immunogenicity - IgG
Percentage of participants attaining or exceeding a concentration of 0.2, 0.5, 1 and 2 µg/mL of serotype-specific IgG. The rate will be assessed overall and stratified by baseline seropositivity.
Time frame: Day 1 baseline collection and 4-weeks post dose collection
Immunogenicity - IgG
Geometric mean concentration (GMC) of GBS-06 serotype specific IgG
Time frame: Day 1 baseline collection and 4-weeks post dose collection
Immunogenicity - IgG
Geometric mean fold-rise (GMFR) of GBS-06 serotype specific IgG
Time frame: Day 1 baseline collection and 4-weeks post dose collection
Immunogenicity - IgG
Rank of IVT GBS-06 dosage levels according to the serotype-specific seroconversion percentages and GMFR
Time frame: Day 1 baseline collection and 4-weeks post dose collection
Immunogenicity - IgG
Difference in serotype-specific seroconversion percentage for each IVT GBS-06 dosage level and placebo.
Time frame: Day 1 baseline collection and 4-weeks post dose collection
Immunogenicity - IgG
Difference in percentage of participants attaining or exceeding a concentration of 0.2, 0.5, 1, and 2 µg/mL of serotype specific IgG for each IVT GBS-06 dosage level and placebo.
Time frame: Day 1 baseline collection and 4-weeks post dose collection
Immunogenicity
GMC serotype-specific ratio between each IVT GBS-06 dosage level and placebo.
Time frame: Day 1 baseline collection and 4-weeks post dose collection
Immunogenicity
GMFR serotype-specific ratio between each IVT GBS-06 dosage level and placebo.
Time frame: Day 1 baseline collection and 4-weeks post dose collection
Immunogenicity - OPA
Post vaccination IVT GBS-06 serotype specific OPA geometric mean titer (GMT) assessed overall and stratified by baseline seropositivity. OPA seropositivity cut off will be based on LLOQ for each serotype calculated in µg/ml.
Time frame: Day 1 baseline collection and 4-weeks post dose collection
Immunogenicity - OPA
IVT GBS-06 serotype-specific OPA GMFR from baseline
Time frame: Day 1 baseline collection and 4-weeks post dose collection
Immunogenicity - OPA
IVT GBS-06 serotype-specific OPA GMT ratio between each IVT GBS-06 level and placebo.
Time frame: Day 1 baseline collection and 4-weeks post dose collection