Clinical trial NCT03765073: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Group B Streptococcus Infections
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2018-12-05
Enrollment: 1208
Sex: ALL
Minimum age (years): 0
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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).
timeFrame: Day 7
measure: 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).
timeFrame: Day 7
measure: Percentages of nonpregnant women reporting adverse events (AEs) through 1 month following administration of the primary and booster doses of investigational product.
timeFrame: 1 month following administration of investigational product
measure: Percentages of nonpregnant women reporting SAEs through 6 months following administration of the primary dose of investigational product.
timeFrame: 6 months following administration of investigational product
measure: 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.
timeFrame: 2 weeks following administration of investigational product
measure: Percentages of maternal participants reporting prompted local reactions within 7 days following administration of investigational product (pain at the injection site, redness, and swelling).
timeFrame: Day 7
measure: 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).
timeFrame: Day 7
measure: Percentages of maternal participants reporting AEs through 1 month after administration of investigational product.
timeFrame: 1 month after administration of investigational product
measure: 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).
timeFrame: 12 months after delivery
measure: Percentages of maternal participants with each delivery outcome (live birth, delivery mode).
timeFrame: Delivery
measure: Percentages of infant participants with specific birth outcomes.
timeFrame: Birth
measure: Percentages of infant participants with AEs from birth to 6 weeks of age.
timeFrame: 6 weeks of age
measure: 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.
timeFrame: 12 months of age
measure: Percentages of nonpregnant women reporting SAEs approximately 7 to 12 months following the booster doses of investigational product.
timeFrame: 7 to 12 months following administration of investigational product
measure: Percentages of nonpregnant women reporting medically attended adverse events (MAEs) through 6 months following administration of the primary dose of investigational product.
timeFrame: 6 months following administration of investigational product
measure: Percentages of nonpregnant women reporting medically attended adverse events (MAEs) approximately 7 to 12 months following the booster doses of investigational product.
timeFrame: 7 to 12 months following administration of investigational product
Secondary outcomes:
measure: Group B streptococcus (GBS) serotype-specific IgG geometric mean concentrations (GMCs) 1 month after vaccination in nonpregnant women.
timeFrame: 1 month after vaccination
measure: GBS serotype-specific IgG GMCs measured at 2 weeks after vaccination in maternal participants.
timeFrame: 2 weeks after vaccination
measure: GBS serotype-specific IgG GMCs in infant participants measured at birth.
timeFrame: Birth
measure: GBS serotype-specific OPA GMTs in infant participants measured at birth.
timeFrame: Birth
measure: GBS serotype-specific IgG GMCs measured at 1 month after vaccination in maternal participants.
timeFrame: 1 month after vaccination
measure: GBS serotype-specific IgG GMCs measured at delivery in maternal participants.
timeFrame: Delivery
measure: GBS serotype-specific OPA GMTs measured at 1 month after vaccination in maternal participants.
timeFrame: 1 month after vaccination
measure: GBS serotype-specific OPA GMTs measured at delivery in maternal participants.
timeFrame: Delivery
measure: GBS serotype-specific IgG geometric mean concentrations (GMCs) measured before a booster vaccination in nonpregnant women
timeFrame: Before booster vaccination
measure: GBS serotype-specific IgG geometric mean concentrations (GMCs) measured 1 month after a booster vaccination in nonpregnant women
timeFrame: 1 month after booster vaccination
measure: GBS serotype-specific IgG geometric mean concentrations (GMCs) measured 3 months after a booster vaccination in nonpregnant women
timeFrame: 3 months after booster vaccination
measure: GBS serotype-specific IgG geometric mean concentrations (GMCs) measured 6 months after a booster vaccination in nonpregnant women
timeFrame: 6 months after booster vaccination
Other outcomes:
Locations:
city: Mobile
country: United States
facility: MedPharmics, LLC
state: Alabama
city: Mobile
country: United States
facility: Velocity Clinical Research
state: Alabama
city: Phoenix
country: United States
facility: Velocity Clinical Research, Covington
state: Arizona
city: Phoenix
country: United States
facility: Velocity Clinical Research, Phoenix
state: Arizona
city: Phoenix
country: United States
facility: MedPharmics, LLC
state: Arizona
city: Lancaster
country: United States
facility: Chemidox Clinical Trials Inc.
state: California
city: Lancaster
country: United States
facility: Chemidox Clinical Trials Inc
state: California
city: Washington
country: United States
facility: Emerson Clinical Research Institute
state: District of Columbia
city: Washington
country: United States
facility: Emerson Clinical Research Institute
state: District of Columbia
city: Idaho Falls
country: United States
facility: Clinical Research Prime
state: Idaho
city: Rexburg
country: United States
facility: Clinical Research Prime Rexburg
state: Idaho
city: Covington
country: United States
facility: Lakeview Regional Medical Center
state: Louisiana
city: Covington
country: United States
facility: MedPharmics
state: Louisiana
city: Covington
country: United States
facility: St. Tammany Parish Hospital
state: Louisiana
city: Covington
country: United States
facility: Velocity Clinical Research, Covington
state: Louisiana
city: Hammond
country: United States
facility: North Oaks Medical Center
state: Louisiana
city: Hammond
country: United States
facility: North Oaks Obstetrics & Gynecology
state: Louisiana
city: Lafayette
country: United States
facility: MedPharmics, LLC (Recruitment Call Center)
state: Louisiana
city: Lafayette
country: United States
facility: MedPharmics, LLC
state: Louisiana
city: Slidell
country: United States
facility: MedPharmics, LLC
state: Louisiana
city: Slidell
country: United States
facility: Velocity Clinical Research, Slidell
state: Louisiana
city: Slidell
country: United States
facility: Velocity Clinical Research
state: Louisiana
city: Missoula
country: United States
facility: Boeson Research
state: Montana
city: Missoula
country: United States
facility: Community Hospital
state: Montana
city: Missoula
country: United States
facility: The Birth Center
state: Montana
city: Hastings
country: United States
facility: Meridian Clinical Research
state: Nebraska
city: Lincoln
country: United States
facility: Frontier Pediatric Care (Follow-Up Visits for Infant Participants)
state: Nebraska
city: Lincoln
country: United States
facility: Bryan Women's Care Physicians (Maternal Visits & Obstetric Exams)
state: Nebraska
city: Lincoln
country: United States
facility: Be Well Clinical Studies
state: Nebraska
city: Norfolk
country: United States
facility: Meridian Clinical Research, LLC
state: Nebraska
city: Albuquerque
country: United States
facility: MedPharmics, LLC
state: New Mexico
city: Cincinnati
country: United States
facility: Velocity Clinical Research
state: Ohio
city: Summerville
country: United States
facility: Lowcountry Women's Specialists
state: South Carolina
city: Summerville
country: United States
facility: Summerville Medical Center
state: South Carolina
city: Summerville
country: United States
facility: Coastal Pediatric Research
state: South Carolina
city: Austin
country: United States
facility: St. Davids Medical Center
state: Texas
city: Austin
country: United States
facility: Tekton Research, Inc
state: Texas
city: Norfolk
country: United States
facility: Sentara Leigh Hospital
state: Virginia
city: Norfolk
country: United States
facility: The Group for Women
state: Virginia
city: Norfolk
country: United States
facility: Tidewater Physicians for Women
state: Virginia
city: Johannesburg
country: South Africa
facility: Wits Reproductive Health and HIV Institute
state: Gauteng
city: Soweto
country: South Africa
facility: Respiratory and Meningeal Pathogens Research Unit (RMPRU)
state: Gauteng
city: Coronationville
country: South Africa
facility: Empilweni Services and Research Unit (ESRU)
state: Johannesburg
city: Parktown
country: South Africa
facility: Charlotte Maxeke Johannesburg Academic Hospital
state: Johannesburg
city: Khayelitsha
country: South Africa
facility: Khayelitsha Hospital
state: Western CAPE
city: Khayelitsha
country: South Africa
facility: Michael Mapongwana Community Health Centre
state: Western CAPE
city: Khayelitsha
country: South Africa
facility: Site B
state: Western CAPE
city: Parow Valley
country: South Africa
facility: FAMCRU
state: Western CAPE
city: London
country: United Kingdom
facility: St George's University Hospitals NHS Foundation Trust
state: Tooting
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: