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 Adults 18 To 49 Years Of Age

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 ADULTS 18 TO 49 YEARS OF AGE

This is the Phase 1/2 first-in-human, randomized, placebo-controlled, observer-blinded study evaluating the investigational multivalent group B streptococcus vaccine. Healthy adults aged 18 to 49 years of age with no history of group B streptococcal vaccination will be randomized to receive either a single intramuscular dose of multivalent group B streptococcus vaccine (various formulations at 3 dose levels) or a placebo (saline control).

Study Overview

• Status: Completed
• Conditions: Group B Streptococcal Infections
• Intervention / Treatment: Biological: Multivalent group B streptococcus vaccine; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 365
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Atlanta
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Kentucky Pediatric / Adult Research
  • Utah
    • Salt Lake City, Utah, United States, 84109
      • J. Lewis Research, Inc. / Foothill Family Clinic
    • Salt Lake City, Utah, United States, 84121
      • J. Lewis Research, Inc. / Foothill Family Clinic South

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy adults (male and female) 18 to 49 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.
2. Negative urine pregnancy test at Visit 1 for all female subjects who are of childbearing potential.

Exclusion Criteria:

1. Male subjects and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for at least 3 months after the last dose of investigational product.
2. Acute or chronic medical or psychiatric condition 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 subject inappropriate for entry into this study. Chronic medical conditions include human immunodeficiency virus, chronic hepatitis B virus (HBV) infection (HBV surface antigen positive), and/or hepatitis C virus infection.
3. History of severe adverse reaction and/or severe allergic reaction (eg, anaphylaxis) to any vaccine.
4. History of microbiologically proven invasive disease caused by group B streptococcus (Streptococcus agalactiae).
5. Previous vaccination with any licensed or investigational group B streptococcus vaccine, or planned receipt during the subject's participation in the study (through the last blood draw).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lowest dose formulation a; Multivalent group B streptococcus vaccine	Biological: Multivalent group B streptococcus vaccine; Various formulations at three dose levels
Experimental: Middle dose formulation a; Multivalent group B streptococcus vaccine	Biological: Multivalent group B streptococcus vaccine; Various formulations at three dose levels
Experimental: Highest dose formulation a; Multivalent group B streptococcus vaccine	Biological: Multivalent group B streptococcus vaccine; Various formulations at three dose levels
Experimental: Lowest dose formulation b; Multivalent group B streptococcus vaccine	Biological: Multivalent group B streptococcus vaccine; Various formulations at three dose levels
Experimental: Middle dose formulation b; Multivalent group B streptococcus vaccine	Biological: Multivalent group B streptococcus vaccine; Various formulations at three dose levels
Experimental: Highest dose formulation b; Multivalent group B streptococcus vaccine	Biological: Multivalent group B streptococcus vaccine; Various formulations at three dose levels
Placebo Comparator: Placebo; Saline control	Biological: Placebo; Saline Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Clinical Laboratory Abnormalities at 1-Week After Vaccination as Measured by Food and Drug Administration (FDA) Grade	Hemoglobin:Grade(G)1: 11-13.5g/dL, G2:9.5-12.4g/dL,G3:8-10.4 g/dL, G4:<8.0 g/dL; leukocyte increase:G1: 10.8-15*10^9/Liter[L],G2:>15-20*10^9/L, G3:>20-25*10^9/L, G4:>25*10^9/L,leukocyte decrease: G1: 2.5-3.5*10^9/L, G2: 1.5-<2.5*10^9/L, G3: 1-<1.5*10^9/L, G4:<1*10^9/L; neutrophil decrease:G1: 1.5-2*10^9/L, G2:1-<1.5*10^9/L, G3:0.5-<1*10^9/L,G4:<0.5*10^9/L; platelets:G1: 125-140*10^9/L, G2:100-124*10^9/L, G3:25-99*10^9/L, G4:<25*10^9/L; eosinophils: G1: 0.65-1.5*10^9/L, G2:>1.5-5*10^9/L, G3:>5*10^9/L, G4: hypereosinophilic;alanine aminotransferase,aspartate aminotransferase:G1: 1.1-2.5 *ULN, G2:2.6-5.0*ULN, G3:5.1-10*ULN, G4:>10*ULN; alkaline phosphatase:G1: 1.1-2*ULN, G2:2.1-3*ULN, G3:3.1-10*ULN, G4:>10*ULN; Bilirubin:G1: 1.1-1.5*ULN, G2: 1.26-2*ULN,G3: 1.51-3.0*ULN,G4:>1.75*ULN;blood urea nitrogen:G1:23-26mg/dL,G2:27-31mg/dL,G3:>31mg/dL, G4:dialysis;creatinine:G1:1.5-1.7mg/dL,G2:1.8-2mg/dL,G3:2.1-2.5 mg/dL,G4:dialysis.Categories with>=1 participant with abnormality are reported only.	1 week after vaccination
Percentage of Participants With Local Reactions by Maximum Severity Within 14 Days After Vaccination	Local reactions were collected by using an e-diary and included redness, swelling and pain at injection site. Redness and swelling were graded as: mild (2.5-5.0 centimeter [cm]), moderate (greater than [>] 5.0-10.0 cm) and severe (>10.0 cm), grade 4 for redness (necrosis or exfoliative dermatitis) and grade 4 for swelling (necrosis). Pain at injection site was graded as: mild (did not interfere with activity), moderate (repeated use of nonnarcotic pain reliever >24 hours or interfered with activity), severe (any use of narcotic pain reliever or prevented daily activity which resulted in missed days of work or school or was otherwise incapacitating, or included use of narcotics for analgesia), and grade 4 (required emergency room visit or hospitalization). The maximum severity (highest grading) of each location reaction within 14 days of vaccination was derived.	Within 14 days after vaccination
Percentage of Participants With Systemic Events by Maximum Severity Within 14 Days After Vaccination	Fever:38.0-38.4 degree Celsius (C),38.5-38.9 degree C,39.0-40.0 degree C,>40.0 degree C;nausea/vomiting:mild(not interfered with activity/1-2times in 24 hours[hr]),moderate(some interference with activity/>2times in 24hr),severe(prevented daily activity;required intravenous hydration); diarrhea:mild(2-3 loose stools in 24hr),moderate(4-5 loose stools in 24hr),severe(>=6 loose stools in 24 hr); headache:mild(not interfered with activity),moderate(repeated use of non-narcotic pain reliever >24 hr/some interference with activity),severe(significant;any use of narcotic pain reliever/prevented daily activity);fatigue,muscle and joint pain:mild(not interfered with activity), moderate(some interference with activity),severe(significant;prevented daily activity).Prevented daily activity=missed days of work, school/otherwise incapacitating/use of narcotics for analgesia.Nausea/vomiting,diarrhea,headache,fatigue/tiredness,muscle and joint pain: grade 4=emergency room visit or hospitalization.	Within 14 days after vaccination
Percentage of Participants With Adverse Events (AEs) Within 1 Month After Vaccination	An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or that was considered to be an important medical event. AEs included both non-serious AEs and SAEs.	Within 1 month after vaccination
Percentage of Participants With Serious Adverse Events (SAEs) Within 6 Month After Vaccination	An AE was any untoward medical occurrence in a participant in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or that was considered to be an important medical event.	Within 6 months after vaccination
Percentage of Participants With Medically Attended Adverse Events (MAEs) Within 6 Months After Vaccination	An AE was any untoward medical occurrence in a participant in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or that was considered to be an important medical event. An MAE was defined as a non serious AE (AE other than SAE) that resulted in an evaluation at a medical facility.	Within 6 months after vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GBS6 Serotype-Specific Immunoglobulin G (IgG) Geometric Mean Concentrations (GMCs) at 1 Month After Vaccination	Serotypes used for evaluation were: Ia, Ib, II, III, IV, and V.	1 month after vaccination

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Absalon J, Segall N, Block SL, Center KJ, Scully IL, Giardina PC, Peterson J, Watson WJ, Gruber WC, Jansen KU, Peng Y, Munson S, Pavliakova D, Scott DA, Anderson AS. Safety and immunogenicity of a novel hexavalent group B streptococcus conjugate vaccine in healthy, non-pregnant adults: a phase 1/2, randomised, placebo-controlled, observer-blinded, dose-escalation trial. Lancet Infect Dis. 2021 Feb;21(2):263-274. doi: 10.1016/S1473-3099(20)30478-3. Epub 2020 Sep 3.

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2017
• Primary Completion (Actual): June 25, 2018
• Study Completion (Actual): June 25, 2018

Study Registration Dates

• First Submitted: May 26, 2017
• First Submitted That Met QC Criteria: May 26, 2017
• First Posted (Actual): May 31, 2017

Study Record Updates

• Last Update Posted (Actual): July 2, 2019
• Last Update Submitted That Met QC Criteria: June 13, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Streptococcal Infections
• Other Study ID Numbers: C1091001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No