Safety and Immunogenicity of the Liquid Formulation of Group B Streptococcus Trivalent Vaccine and of the Lyophilized Formulation of Group B Streptococcus Trivalent Vaccine

Study Overview
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Brief Summary
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The purpose of the present study is to assess and compare in healthy non-pregnant women 18 to 40 years of age the safety and immunogenicity of a liquid formulation of Group B Streptococcus (GBS) Trivalent Vaccine (not requiring reconstitution prior to administration), and of the lyophilized formulation of GBS Trivalent Vaccine, administered in non-pregnant and pregnant women in the clinical development program to date.

Official Title
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A Phase II, Randomized, Comparative, Observer-Blind, Multi-Center Study Evaluating the Safety and Immunogenicity of the Liquid Formulation of Group B Streptococcus Trivalent Vaccine and of the Lyophilized Formulation of Group B Streptococcus Trivalent Vaccine in Healthy Non-Pregnant Women Aged 18 to 40 Years

Conditions
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Infections, Streptococcal, Streptococcal Infections

Intervention / Treatment
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* Biological: GBS Vaccine
* Biological: GBS Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy females 18-40 years of age, inclusive. Individuals who have given written consent after the nature of the study has been explained according to local regulatory requirements. Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator. Individuals who can comply with all study procedures and are available for follow-up. Exclusion Criteria: Individuals who are pregnant (urine pregnancy test at Study Day 1) or who anticipate becoming pregnant prior to the end of the study, Day 181 Visit. Individuals of childbearing potential, heterosexually active, and has not used any of the acceptable contraceptive methods for at least 2 months prior to study entry and who will not continue to use acceptable contraceptive methods through to the end of the study, Day 181 Visit. Of childbearing potential is defined as status post onset of menarche and not meeting any of the following conditions: menopausal for at least 2 years, status after bilateral tubal ligation for at least 1 year, status after bilateral oophorectomy, or status after hysterectomy. Acceptable birth control methods are defined as one or more of the following: hormonal contraceptive (such as oral, injection, transdermal patch, implant, cervical ring); barrier (condom with spermicide or diaphragm with spermicide) each and every time during intercourse; intrauterine device (IUD); monogamous relationship with vasectomized partner who was vasectomized for at least six months prior to the subject's study entry; or abstinence/no sexual intercourse. Individuals who are nursing (breastfeeding). Individuals who have participated in any clinical trial with another investigational product 30 days prior to first study visit or who intend to participate in another trial prior to the end of the study, Day 181 Visit. Individuals who have had a previous immunization with a vaccine containing Group B Streptococcus antigens. Individuals who receive: live vaccine 30 days prior to study vaccination inactivated vaccines 15 days prior to study vaccination any vaccines within 30 days after study vaccination exception: an inactivated influenza vaccine may be administered up to 7 days prior to study vaccination or 7 days after study vaccination Individuals with a fever (oral temperature ≥ 38°C) within 3 days prior to Study Day 1. Individuals with acute or chronic infection(s) (e.g. requiring systemic antibiotic treatment or antiviral therapy) within 7 days prior to Study Day 1. Individuals with a history of severe allergic reactions after previous vaccination or medication such as anaphylactic shock, asthma, urticaria, or other allergic reaction or hypersensitivity to any vaccine component. Individuals with known or suspected impairment of the immune system including known or suspected HIV infection or HIV-related disease, a history of or an active autoimmune disorder and receipt of immunosuppressive therapy. Long term use of glucocorticoids, including oral or parenteral prednisone ≥ 20 mg/day or equivalent for more than 2 consecutive weeks (or 2 weeks total) within 30 days prior to enrollment. Use of inhaled, intranasal, intra-articular, or topical corticosteroids is allowed. Individuals who have received blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the past 12 weeks. Individuals with any progressive or severe neurologic disorder, seizure disorder, epilepsy or Guillain-Barré syndrome. Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the subject's ability to participate in the study. Individuals who are not able to comprehend and to follow all required study procedures for the whole period of the study. Individuals with history or any illness that, in the opinion of the investigator, might interfere with results of the study or pose additional risk to subjects due to participation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liquid GBS trivalent vaccine<br>Healthy non-pregnant women aged 18-40 years that received a single dose of liquid GBS trivalent vaccine | Biological: GBS Vaccine<br>* Liquid formulation of a vaccine containing polysaccharide capsules from serotypes Ia, Ib, and III of the Group B Streptococcus<br>|
| Active Comparator: Lyophilized GBS trivalent vaccine<br>Healthy non-pregnant women aged 18-40 years that received a single dose of lyophilized GBS trivalent vaccine | Biological: GBS Vaccine<br>* Lyophilized formulation of a vaccine containing polysaccharide capsules from serotypes Ia, Ib, and III of the Group B Streptococcus<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of Serotype Ia GBS IgG Levels in Healthy Non-pregnant Women | To evaluate serotype-specific Ia GBS serum IgG antibody levels (anti-Ia) in healthy non-pregnant women when administered with the liquid GBS trivalent vaccine formulation or the lyophilized GBS trivalent vaccine formulation. Antibody concentrations were measured by Enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). | At Day 31 after a single vaccination | 
| Concentration of Serotype III GBS IgG Levels in Healthy Non-pregnant Women | To evaluate serotype-specific III GBS serum IgG antibody levels (anti-III) in healthy non-pregnant women when administered with the liquid GBS trivalent vaccine formulation or the lyophilized GBS trivalent vaccine formulation. Antibody concentrations were measured by Enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). | At Day 31 after a single vaccination | 
| Concentration of Serotype Ib GBS IgG Levels in Healthy Non-pregnant Women | To evaluate serotype-specific Ib GBS serum IgG antibody levels (anti-Ib) in healthy non-pregnant women when administered with the liquid GBS trivalent vaccine formulation or the lyophilized GBS trivalent vaccine formulation. Geometric mean concentrations (GMCs) were measured and expressed in micrograms per milliliter (μg/mL). As the singleton ELISA was no longer in use at the time of serotype Ib testing, results were obtained using multiplex immunoassay. | At Day 31 after a single vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Safety was assessed as the number of subjects who reported solicited local and solicited systemic AEs following a single injection with either liquid or lyophilized GBS trivalent vaccine formulations. | From 6 hours through Day 7 post-vaccination | 
| Number of Subjects Reporting Any Unsolicited AEs | Safety was assessed as the number of subjects who reported unsolicited AEs following a single injection with either liquid or lyophilized GBS trivalent vaccine formulations. | From Day 1 to Day 181 (end of the study) | 
| Number of Subjects Reporting Any Serious Adverse Events (SAEs) | Safety was assessed as the number of subjects who reported SAEs following a single injection with either liquid or lyophilized GBS trivalent vaccine formulations. | From Day 1 to Day 181 (end of the study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GBS, vaccine comparability, Group B Strep