Trial To Evaluate The Safety, Tolerability, And Immunogenicity Of A Multivalent Group B Streptococcus Vaccine In Healthy Nonpregnant Women And Pregnant Women And Their Infants

Study Overview
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Brief Summary
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Phase 1/2, randomized, placebo-controlled, observer-blinded study will evaluate the safety, tolerability and immunogenicity of the investigational multivalent group B streptococcus vaccine administered at one dose level (various formulations) in healthy nonpregnant women (various formulations at one dose level), and then in healthy pregnant women (various formulations at three dose levels), and finally in healthy pregnant women at a selected dose level/formulation.

Official Title
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A PHASE 1/2, RANDOMIZED, PLACEBO-CONTROLLED, OBSERVER-BLINDED TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A MULTIVALENT GROUP B STREPTOCOCCUS VACCINE IN HEALTHY NONPREGNANT WOMEN AND PREGNANT WOMEN 18 TO 40 YEARS OF AGE AND THEIR INFANTS

Conditions
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Group B Streptococcus Infections

Intervention / Treatment
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* Biological: Multivalent Group B streptococcus vaccine
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Stage 1 Nonpregnant Women: Healthy nonpregnant females 18 to 40 years of age at enrollment who are determined by medical history, physical examination, and clinical judgment of the investigator to be eligible for inclusion in the study. Negative urine pregnancy test at Visit 1 (prior to vaccination). Documented negative HIV, hepatitis C virus (HCV), and acute or chronic hepatitis B virus (HBV) infection at screening. Inclusion Criteria Stage 1 Booster Vaccination: Participant must have received investigational product at Visit 1. Healthy nonpregnant female determined by medical history, physical examination, and clinical judgment of the investigator to be eligible for booster vaccination and received investigational product at Visit 1. Negative urine pregnancy test at Visit 6 (prior to vaccination). Documented negative HIV, hepatitis C virus (HCV), and acute or chronic hepatitis B virus (HBV) infection at screening. Inclusion Criteria Stage 2 and 3 Maternal Participants: Healthy females >=18 and <=40 years of age who are >=27 0/7 (Stage 2) or >=24 0/7 (Stage 3) to <=35 6/7 weeks' gestation on the day of planned vaccination, with an uncomplicated, singleton pregnancy, and at no increased risk for complications and no significant fetal abnormalities observed on ultrasound performed at any time prior to study entry and/or at the screening visit. Documented negative HIV antibody, HBV surface antigen, HCV antibody, and syphilis tests at screening. Inclusion Criteria Stage 2 and 3 Infant Participants: Evidence of a signed and dated ICD signed by the parent(s). Parent(s) willing and able to comply with scheduled visits, investigational plan, laboratory tests, and other study procedures. Exclusion Criteria Stage 1 Nonpregnant Women: Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the investigational product or any diphtheria toxoid-containing or CRM197 containing vaccine. History of microbiologically proven invasive disease caused by GBS (S agalactiae). Previous vaccination with any licensed or investigational GBS vaccine (other than GBS6 received as a primary vaccination at Visit 1), or planned receipt during the participant's participation in the study (through the last blood draw). Exclusion criteria Stage 2 and 3 Maternal Participants: Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the investigational product or any diphtheria toxoid-containing or CRM197 containing vaccine. History of microbiologically proven invasive disease caused by GBS (S agalactiae). Previous vaccination with any licensed or investigational group B streptococcus vaccine, or planned receipt during the participant's participation in the study (through the last blood draw). Prepregnancy body mass index (BMI) of ≥40 kg/m2. If prepregnancy BMI is not available, the BMI at the time of the first obstetric visit during the current pregnancy may be used. A prior history of or current pregnancy complications or abnormalities that will increase the risk associated with the participant's participation. Major illness of the mother or conditions of the fetus that, in the investigator's judgment, will substantially increase the risk associated with the participant's participation in, and completion of, the study or could preclude the evaluation of the participant's response. Exclusion criteria Stage 2 and 3 Infant Participants: Infant who is a direct descendant (eg, child or grandchild) of the study personnel.

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stage 1 - Highest dose formulation a<br>Multivalent group B streptococcus vaccine - Stage 1 Nonpregnant women | Biological: Multivalent Group B streptococcus vaccine<br>* Various formulations at three dose levels<br>|
| Experimental: Stage 1 - Highest dose formulation b<br>Multivalent group B streptococcus vaccine - Stage 1 Nonpregnant women | Biological: Multivalent Group B streptococcus vaccine<br>* Various formulations at three dose levels<br>|
| Experimental: Stage 2 - Lowest dose formulation a<br>Multivalent group B streptococcus vaccine - Stage 2 Pregnant women | Biological: Multivalent Group B streptococcus vaccine<br>* Various formulations at three dose levels<br>|
| Experimental: Stage 2 - Lowest dose formulation b<br>Multivalent group B streptococcus vaccine - Stage 2 Pregnant women | Biological: Multivalent Group B streptococcus vaccine<br>* Various formulations at three dose levels<br>|
| Experimental: Stage 2 - Middle dose formulation a<br>Multivalent group B streptococcus vaccine - Stage 2 Pregnant women | Biological: Multivalent Group B streptococcus vaccine<br>* Various formulations at three dose levels<br>|
| Experimental: Stage 2 - Middle dose formulation b<br>Multivalent group B streptococcus vaccine - Stage 2 Pregnant women | Biological: Multivalent Group B streptococcus vaccine<br>* Various formulations at three dose levels<br>|
| Experimental: Stage 2 - Highest dose formulation a<br>Multivalent group B streptococcus vaccine - Stage 2 Pregnant women | Biological: Multivalent Group B streptococcus vaccine<br>* Various formulations at three dose levels<br>|
| Experimental: Stage 2 - Highest dose formulation b<br>Multivalent group B streptococcus vaccine - Stage 2 Pregnant women | Biological: Multivalent Group B streptococcus vaccine<br>* Various formulations at three dose levels<br>|
| Experimental: Stage 3 - Selected dose and formulation<br>Multivalent group B streptococcus vaccine - Stage 3 Pregnant women | Biological: Multivalent Group B streptococcus vaccine<br>* Various formulations at three dose levels<br>|
| Placebo Comparator: Stage 1 Placebo<br>Saline control | Biological: Placebo<br>* Saline control<br>|
| Placebo Comparator: Stage 2 Placebo<br>Saline control | Biological: Placebo<br>* Saline control<br>|
| Placebo Comparator: Stage 3 Placebo<br>Saline control | Biological: Placebo<br>* Saline control<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of nonpregnant women reporting prompted local reactions within 7 days following primary and booster doses of investigational product (pain at the injection site, redness, and swelling). | Describe prompted local reactions for nonpregnant women following investigational product administration. | Day 7 | 
| Percentages of nonpregnant women reporting prompted systemic events within 7 days following primary and booster doses of investigational product (fever, nausea/vomiting, diarrhea, headache, fatigue/tiredness, muscle pain, and joint pain). | Describe prompted systemic events for nonpregnant women following investigational product administration. | Day 7 | 
| Percentages of nonpregnant women reporting adverse events (AEs) through 1 month following administration of the primary and booster doses of investigational product. | Describe AEs for nonpregnant women occurring through 1 month following administration of investigational product. | 1 month following administration of investigational product | 
| Percentages of nonpregnant women reporting SAEs through 6 months following administration of the primary dose of investigational product. | Describe SAEs for nonpregnant women through 6 months following administration of investigational product. | 6 months following administration of investigational product | 
| Percentages of sentinel-cohort maternal participants (Stage 2 only) with clinical laboratory abnormalities following administration of investigational product at the 2-week follow-up visit. | Describe clinical laboratory abnormalities for maternal participants (Stage 2 only) following administration of investigational product at 2-week follow-up visit. | 2 weeks following administration of investigational product | 
| Percentages of maternal participants reporting prompted local reactions within 7 days following administration of investigational product (pain at the injection site, redness, and swelling). | Describe prompted local reactions for maternal participants within 7 days following administration of investigational product (pain at the injection site, redness, and swelling). | Day 7 | 
| Percentages of maternal participants reporting prompted systemic events within 7 days following administration of investigational product (fever, nausea/vomiting, diarrhea, headache, fatigue/tiredness, muscle pain, and joint pain). | Describe prompted systemic events for maternal participants within 7 days following administration of investigational product (fever, nausea/vomiting, diarrhea, headache, fatigue/tiredness, muscle pain, and joint pain). | Day 7 | 
| Percentages of maternal participants reporting AEs through 1 month after administration of investigational product. | Describe AEs through 1 month after administration of investigational product. | 1 month after administration of investigational product | 
| Percentages of maternal participants with SAEs, MAEs, and obstetric complications (prepartum, intrapartum, and postpartum) throughout the study (Visit 1 through the 12-month postdelivery study visit). | Describe SAEs, MAEs, and obstetric complications (prepartum, intrapartum, and postpartum) for maternal participants throughout the study (Visit 1 through the 12-month postdelivery study visit). | 12 months after delivery | 
| Percentages of maternal participants with each delivery outcome (live birth, delivery mode). | Describe delivery outcomes (live birth, delivery mode) for maternal participants. | Delivery | 
| Percentages of infant participants with specific birth outcomes. | Describe specific birth outcomes for infant participants. | Birth | 
| Percentages of infant participants with AEs from birth to 6 weeks of age. | Describe AEs for infant participants from birth to 6 weeks of age. | 6 weeks of age | 
| Percentages of infant participants with SAEs, AEs of special interest (major congenital anomalies, developmental delay, and suspected or confirmed GBS infection), and MAEs through 12 months of age. | Describe SAEs, AEs of special interest (major congenital anomalies, developmental delay, and suspected or confirmed GBS infection), and MAEs for infant participants through 12 months of age. | 12 months of age | 
| Percentages of nonpregnant women reporting SAEs approximately 7 to 12 months following the booster doses of investigational product. | Describe SAEs for nonpregnant women 7 to 12 months following administration of investigational product. | 7 to 12 months following administration of investigational product | 
| Percentages of nonpregnant women reporting medically attended adverse events (MAEs) through 6 months following administration of the primary dose of investigational product. | Describe MAEs for nonpregnant women through 6 months following administration of investigational product. | 6 months following administration of investigational product | 
| Percentages of nonpregnant women reporting medically attended adverse events (MAEs) approximately 7 to 12 months following the booster doses of investigational product. | Describe MAEs for nonpregnant women 7 to 12 months following administration of investigational product. | 7 to 12 months following administration of investigational product | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Group B streptococcus (GBS) serotype-specific IgG geometric mean concentrations (GMCs) 1 month after vaccination in nonpregnant women. | Describe GBS serotype-specific IgG geometric mean concentrations (GMCs) 1 month after vaccination in nonpregnant women. | 1 month after vaccination | 
| GBS serotype-specific IgG GMCs measured at 2 weeks after vaccination in maternal participants. | Describe GBS serotype-specific IgG GMCs measured at 2 weeks after vaccination in maternal participants. | 2 weeks after vaccination | 
| GBS serotype-specific IgG GMCs in infant participants measured at birth. | Describe GBS serotype-specific IgG GMCs in infant participants measured at birth. | Birth | 
| GBS serotype-specific OPA GMTs in infant participants measured at birth. | Describe GBS serotype-specific OPA GMTs in infant participants measured at birth. | Birth | 
| GBS serotype-specific IgG GMCs measured at 1 month after vaccination in maternal participants. | Describe GBS serotype-specific IgG GMCs measured at 1 month after vaccination in maternal participants. | 1 month after vaccination | 
| GBS serotype-specific IgG GMCs measured at delivery in maternal participants. | Describe GBS serotype-specific IgG GMCs measured at delivery in maternal participants. | Delivery | 
| GBS serotype-specific OPA GMTs measured at 1 month after vaccination in maternal participants. | Describe GBS serotype-specific OPA GMTs measured at 1 month after vaccination in maternal participants. | 1 month after vaccination | 
| GBS serotype-specific OPA GMTs measured at delivery in maternal participants. | Describe GBS serotype-specific OPA GMTs measured at delivery in maternal participants. | Delivery | 
| GBS serotype-specific IgG geometric mean concentrations (GMCs) measured before a booster vaccination in nonpregnant women | Describe GBS serotype-specific IgG GMCs measured before a booster vaccination in nonpregnant women | Before booster vaccination | 
| GBS serotype-specific IgG geometric mean concentrations (GMCs) measured 1 month after a booster vaccination in nonpregnant women | Describe GBS serotype-specific IgG GMCs measured 1 month after a booster vaccination in nonpregnant women | 1 month after booster vaccination | 
| GBS serotype-specific IgG geometric mean concentrations (GMCs) measured 3 months after a booster vaccination in nonpregnant women | Describe GBS serotype-specific IgG GMCs measured 3 months after a booster vaccination in nonpregnant women | 3 months after booster vaccination | 
| GBS serotype-specific IgG geometric mean concentrations (GMCs) measured 6 months after a booster vaccination in nonpregnant women | Describe GBS serotype-specific IgG GMCs measured 6 months after a booster vaccination in nonpregnant women | 6 months after booster vaccination |