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

Phase 2

Completed

• Conditions: Group B Streptococcal Infections
• Interventions: Biological: Multivalent group B streptococcus vaccine; Biological: Placebo

• Registration Number: NCT03170609
• Lead Sponsor: Pfizer

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-05-26
• Study First Submitted QC: 2017-05-26
• Study First Posted: 2017-05-31
• Study Start: 2017-06-05
• Primary Completion: 2018-06-25
• Study Completion: 2018-06-25
• Status Verified: 2019-06
• Results First Submitted: 2019-06-13
• Results First Submitted QC: 2019-06-13
• Last Update Submitted: 2019-06-13
• Results First Posted: 2019-07-02
• Last Update Posted: 2019-07-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 365

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Middle dose formulation b	Multivalent group B streptococcus vaccine	Multivalent group B streptococcus vaccine
Highest dose formulation a	Multivalent group B streptococcus vaccine	Multivalent group B streptococcus vaccine
Highest dose formulation b	Multivalent group B streptococcus vaccine	Multivalent group B streptococcus vaccine
Placebo	Placebo	Saline control
Lowest dose formulation a	Multivalent group B streptococcus vaccine	Multivalent group B streptococcus vaccine
Middle dose formulation a	Multivalent group B streptococcus vaccine	Multivalent group B streptococcus vaccine
Lowest dose formulation b	Multivalent group B streptococcus vaccine	Multivalent group B streptococcus vaccine

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Clinical Laboratory Abnormalities at 1-Week After Vaccination as Measured by Food and Drug Administration (FDA) Grade	1 week after vaccination	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.
Percentage of Participants With Local Reactions by Maximum Severity Within 14 Days After Vaccination	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.
Percentage of Participants With Systemic Events by Maximum Severity Within 14 Days After Vaccination	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.
Percentage of Participants With Adverse Events (AEs) Within 1 Month After Vaccination	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.
Percentage of Participants With Serious Adverse Events (SAEs) Within 6 Month After Vaccination	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.
Percentage of Participants With Medically Attended Adverse Events (MAEs) Within 6 Months After Vaccination	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.

Secondary Outcome Measures

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

Trial Locations

Locations (4)

Clinical Research Atlanta; 🇺🇸 Stockbridge, Georgia, United States

Kentucky Pediatric / Adult Research; 🇺🇸 Bardstown, Kentucky, United States

J. Lewis Research, Inc. / Foothill Family Clinic South; 🇺🇸 Salt Lake City, Utah, United States

J. Lewis Research, Inc. / Foothill Family Clinic; 🇺🇸 Salt Lake City, Utah, United States