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

NCT03170609 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: C1091001
• Study Type: interventional
• Target: 365
• Locations: 1 country
• Sites: 4

Brief Summary

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).

Conditions

Group B Streptococcal Infections

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (1)

• GBS6 Serotype-Specific Immunoglobulin G (IgG) Geometric Mean Concentrations (GMCs) at 1 Month After Vaccination

  1 month after vaccination

Study Arms (7)

Lowest dose formulation a

EXPERIMENTAL

Multivalent group B streptococcus vaccine

Biological: Multivalent group B streptococcus vaccine

Middle dose formulation a

EXPERIMENTAL

Multivalent group B streptococcus vaccine

Biological: Multivalent group B streptococcus vaccine

Highest dose formulation a

EXPERIMENTAL

Multivalent group B streptococcus vaccine

Biological: Multivalent group B streptococcus vaccine

Lowest dose formulation b

EXPERIMENTAL

Multivalent group B streptococcus vaccine

Biological: Multivalent group B streptococcus vaccine

Middle dose formulation b

EXPERIMENTAL

Multivalent group B streptococcus vaccine

Biological: Multivalent group B streptococcus vaccine

Highest dose formulation b

EXPERIMENTAL

Multivalent group B streptococcus vaccine

Biological: Multivalent group B streptococcus vaccine

Placebo

PLACEBO COMPARATOR

Saline control

Biological: Placebo

Interventions

Multivalent group B streptococcus vaccine BIOLOGICAL

Various formulations at three dose levels

Highest dose formulation a; Highest dose formulation b; Lowest dose formulation a; Lowest dose formulation b; Middle dose formulation a; Middle dose formulation b

Placebo BIOLOGICAL

Saline Control

Placebo

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Negative urine pregnancy test at Visit 1 for all female subjects who are of childbearing potential.

You may not qualify if:

• 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.
• 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.
• History of severe adverse reaction and/or severe allergic reaction (eg, anaphylaxis) to any vaccine.
• History of microbiologically proven invasive disease caused by group B streptococcus (Streptococcus agalactiae).
• 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).

Sponsors & Collaborators

• Pfizer: lead

Study Sites (4)

Clinical Research Atlanta

Stockbridge, Georgia, 30281, United States

Location

Kentucky Pediatric / Adult Research

Bardstown, Kentucky, 40004, United States

Location

J. Lewis Research, Inc. / Foothill Family Clinic

Salt Lake City, Utah, 84109, United States

Location

J. Lewis Research, Inc. / Foothill Family Clinic South

Salt Lake City, Utah, 84121, United States

Location

Related Publications (1)

• 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.

  PMID: 32891191 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.
• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Streptococcal Infections

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2017
• First Posted: May 31, 2017
• Study Start: June 5, 2017
• Primary Completion: June 25, 2018
• Study Completion: June 25, 2018
• Last Updated: July 2, 2019
• Results First Posted: July 2, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will share

Locations

US (4)