A TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A BOOSTER DOSE OF A GROUP B STREPTOCOCCUS 6 VALENT POLYSACCHARIDE CONJUGATE VACCINE (GBS6) IN HEALTHY ADULTS

Study Overview
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Brief Summary
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This study is an extension to the completed first-in-human C1091001 study (NCT03170609) and is to evaluate the safety and immunogenicity of a single booster vaccine dose of GBS6, administered approximately 2 years or more after a primary GBS6 dose, to healthy adult males and nonpregnant women. The study will determine whether individuals who received a primary dose of GBS6 have additional benefit following a booster dose.

Official Title
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A PHASE 2, OPEN-LABEL TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A BOOSTER DOSE OF A GROUP B STREPTOCOCCUS 6 VALENT POLYSACCHARIDE CONJUGATE VACCINE (GBS6) IN HEALTHY ADULTS

Conditions
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Group B Streptococcal Infections

Intervention / Treatment
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* Biological: Group B streptoccous 6-valent polysaccharide conjugate vaccine (GBS6)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults (male and female) at enrollment who are determined by medical history, physical examination, and clinical judgment of the investigator to be eligible for inclusion in the study. Participants who were enrolled in the C1091001 study, received GBS6, and completed the 1-month blood draw. Exclusion Criteria: Pregnant female participants; breastfeeding female participants; positive urine pregnancy test for women of childbearing potential (WOCBP) at Visit 1 (prior to vaccination); and WOCBP who are, in the opinion of the investigator, sexually active and at risk for pregnancy and fertile men and WOCBP who are unwilling or unable to use effective methods of contraception as outlined in this protocol from the signing of the informed consent until 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 participant 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 (other than GBS6), or planned receipt during the participant's participation in the study (through 6-month telephone call).

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 51 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: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: There are two arms in the study however based on the prior formulation received participants can only be enrolled into one predetermined arm in the study. Participants are assigned by an interactive response technology (IRT) based on prior formulation received.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GBS6 no aluminum phosphate (GBS6 no AlPO4)<br> | Biological: Group B streptoccous 6-valent polysaccharide conjugate vaccine (GBS6)<br>* 2 formulations at 1 dose level<br>* Other names: GBS6;|
| Experimental: GBS6 with aluminum phosphate (GBS6 with AlPO4)<br> | Biological: Group B streptoccous 6-valent polysaccharide conjugate vaccine (GBS6)<br>* 2 formulations at 1 dose level<br>* Other names: GBS6;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Reporting Prompted Local Reactions Within 14 Days Following Booster Dose (Redness, Swelling, and Pain at the Injection Site) | Local reactions were collected by using an e-diary and included pain at injection site, redness, and swelling graded below: pain at injection site: 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), grade 4 (emergency room visit or hospitalization). Redness and swelling were graded as: mild (2.0-5.0 centimeter [cm]), moderate (greater than [>] 5.0-10.0 cm),severe (>10.0 cm), grade 4 for redness (necrosis or exfoliative dermatitis) and grade 4 for swelling (necrosis).Maximum severity (highest grading) of each location reaction within 14 days of vaccination was derived. | Within 14 days after booster dose | 
| Percentage of Participants Reporting Prompted Systemic Events Within 14 Days Following Booster Dose (Fever, Nausea/Vomiting, Diarrhea, Headache, Fatigue, Muscle Pain, and Joint Pain) | Nausea/Vomiting:Mild:No interference with activity or 1-2 times in 24 hours;Moderate:Some interference with activity or>2 times in 24 hours;Severe:Prevented daily activity, required IV hydration.Diarrhea:Mild:2-3 loose stools in 24 hours;Moderate: 4-5 loose stools in 24 hours;Severe:>=6 loose stools in 24 hours.Headache:Mild:No interference with activity;Moderate:Repeated use of nonnarcotic pain reliever >24 hours or some interference with activity;Severe:Significant; any use of narcotic pain reliever or prevents daily activity.Fatigue:Mild:No interference with activity;Moderate: Some interference with activity;Severe: Significant; prevented daily activity.Muscle pain:Mild: No interference with activity;Moderate:Some interference with activity;Severe:Significant;prevented daily activity.Muscle/joint pain:Mild: No interference with activity;Moderate:Some interference with activity;Severe:Significant; prevented daily activity.Grade 4 for all AEs:Emergency visit or hospitalization. | Within 14 days after booster dose | 
| Percentage of Participants Reporting Adverse Events (AEs) Within 1 Month Following Booster Dose | 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 booster dose | 
| Percentage of Participants Reporting Medically Attended Adverse Events (MAEs) Within 6 Months Following Booster Dose | 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 booster dose | 
| Percentage of Participants With Serious Adverse Events (SAEs) Within 6 Months After Booster Dose | 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 booster dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GBS Serotype-Specific IgG Geometric Mean Concentrations (GMC) Measured Before and 1 Month After Booster Dose | Serotypes used for evaluation were: Ia, Ib, II, III, IV, and V. | Before and 1 month after booster dose | 
| GBS Serotype-Specific Opsonophagocytic Activity (OPA) Geometric Mean Titers Measured Before to 1 Month After Booster Dose | OPA for the 6 serotypes (Ia, Ib, II, III, IV, V) were determined in all participants for each blood sample at Day 1 and at 1 month after booster dose. | Within 6 months after primary dose and within 1 month after booster dose | 
| GBS Serotype-Specific IgG Geometric Mean Fold Rise (GMFR) From Before To 1 Month After Booster Dose | IgG for the 6 serotypes (Ia, Ib, II, III, IV, V) were determined in all participants for each blood sample at Day 1 and at 1 month after booster dose. | 1 month after booster dose | 
| GBS Serotype-Specific OPA GMFR Measured Before and 1 Month After Booster Dose | OPA for the 6 serotypes (Ia, Ib, II, III, IV, V) were determined in all participants for each blood sample at Day 1 and at 1 month after booster dose. | 1 month after booster dose | 
| GBS Serotype-Specific IgG GMC Measured 1 Month After Booster Dose Stratified by Baseline Pre-vaccination Status (Before the Primary Dose) | Serotypes used for evaluation were: Ia, Ib, II, III, IV, and V. The pre-vaccination immunogenicity blood draw and booster vaccination were both performed on Day 1. | 1 month after booster dose |