Group B Streptococcus Vaccine in Healthy Females

Study Overview
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Brief Summary
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A Phase I, randomised, single centre, double-blind, placebo-controlled, parallel group study to evaluate the safety, tolerability and immunogenicity of two doses of Group B Streptococcus vaccine.

Detailed Description
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There will be 4 arms in 2 cohorts of 30 subjects. Cohort 1 will receive two 0.5 mL injections, 4 weeks apart, each consisting of 25 μg of GBS-NN and 25 μg of GBS-NN2 (24 subjects) or placebo (6 subjects). Cohort 2 (30 subjects) will receive two 0.5 mL injections, 4 weeks apart, each consisting of 50 μg of GBS-NN and 50 μg of GBS-NN2 (24 subjects) or placebo (6 Subjects). All vaccines will be adsorbed to 500 μg Al3+ as Alhydrogel®. Safety will be assessed after all subjects have completed Visit 4 (Day 8) for Cohort 1, at which point the decision will be made as to whether proceeding with administration of the doses in cohort 2 is appropriate.

Official Title
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A Phase I, Randomised, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Safety, Tolerability and Immunogenicity of Two Doses of Group B Streptococcus Vaccine (GBS-NN/NN2 With Alhydrogel®) in Healthy Female Subjects Aged 18 to 40

Conditions
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Group B Strep Infection

Intervention / Treatment
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* Biological: GBS-NN/NN2 with Alhydrogel® 25
* Biological: Placebo GBS-NN/NN2 with Alhydrogel® 25
* Biological: Placebo GBS-NN/NN2 with Alhydrogel® 50
* Biological: GBS-NN/NN2 with Alhydrogel® 50


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy female subjects aged 18 - 40 years. Body mass index (BMI) ≥18 and ≤30 kg/m2. Subjects weight ≥50kg and ≤100kg at screening. Able to voluntarily provide written informed consent to participate in the study. Subjects are pre-menopausal. Females of childbearing potential must have a negative pregnancy test at screening (β HCG) and prior to each dose. To prevent pregnancy female subjects of childbearing potential must take adequate contraceptive precautions for the entire duration of study participation (up to Day 85). Adequate and highly effective contraceptive precautions include: Established use of oral, injected or implanted hormonal methods of contraception. Placement of an intrauterine device (IUD) or intrauterine system (IUS). Barrier methods of contraception: Condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository. Male sterilisation (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). [For female subjects, the vasectomised male partner should be the sole partner for that subject]. True abstinence, when this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception]. • The chosen contraception method(s) must be followed from the first dose until at least Day 85 of the study. Non-smokers for at least 3 months prior to first study vaccine administration. Exclusion Criteria: Subjects who have received GBS-NN vaccine previously. Subjects with history or presence of significant cardiovascular disease, pulmonary, hepatic, gallbladder or biliary tract, renal, haematological, gastrointestinal, endocrine, immunologic, dermatological, neurological, psychiatric, autoimmune disease or current infection. Pregnant or lactating females. Laboratory values at screening which are deemed by the investigator to be clinically significantly abnormal. Positive drug screen for drugs of abuse or a positive alcohol urine test prior to first dosing unless there is a documented medical explanation for the positive result other than drugs of abuse (e.g., the subject has been prescribed opioids for pain). Positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis C. Participation in a clinical drug study during the 90 days preceding the initial dose in this study. Any significant illness during the 4 weeks preceding check-in for this study (Day 1). Subjects with a history of allergic reactions after previous vaccination. Subjects who have received any vaccine within 30 days of screening, or who are planning to receive a vaccine up to Day 85 of the study. Subjects receiving immunosuppressive therapy in the 6 months prior to screening, taking any short-term medications including over-the-counter (OTC) preparations, within 7 days of the first dose. Chronic medications such as antihypertensives, bronchodilators, oral contraceptives or statins that do not affect the immune system, will be permitted and allowed to continue during the study at the discretion of the Investigator. Paracetamol will be permitted for the treatment of headache or other symptoms. Use of OTC vitamins and dietary supplements is allowed Subjects with tattoos at the proposed site of vaccine administration. Donation of blood or blood products within 90 days prior to vaccine administration or intending to donate blood or blood products within 90 days of the last visit. Subjects who, in the opinion of the Investigator, are unsuitable for participation in the study.

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: GBS-NN/NN2 with Alhydrogel® 25<br>GBS-NN/NN2 with Alhydrogel® 25 mcg intramuscular 2 times with 4 weeks apart | Biological: GBS-NN/NN2 with Alhydrogel® 25<br>* GBS-NN/NN2 with Alhydrogel® vaccine will administered to subjects intramuscular 2 times with 4 weeks apart<br>|
| Placebo Comparator: Placebo GBS-NN/NN2 with Alhydrogel® 25<br>Intramuscular injection with Alhydrogel® 2 times with 4 weeks apart | Biological: Placebo GBS-NN/NN2 with Alhydrogel® 25<br>* GBS-NN/NN2 with Alhydrogel® vaccine will administered to subjects intramuscular 2 times with 4 weeks apart<br>|
| Experimental: GBS-NN/NN2 with Alhydrogel® 50<br>Intramuscular GBS-NN/NN2 with Alhydrogel® injection 50 mcg 2 times with 4 weeks apart | Biological: GBS-NN/NN2 with Alhydrogel® 50<br>* GBS-NN/NN2 with Alhydrogel® vaccine will administered to subjects intramuscular 2 times with 4 weeks apart<br>|
| Placebo Comparator: Placebo GBS-NN/NN2 with Alhydrogel® 50<br>Intramuscular injection with Alhydrogel® 2 times with 4 weeks apart | Biological: Placebo GBS-NN/NN2 with Alhydrogel® 50<br>* GBS-NN/NN2 with Alhydrogel® vaccine will administered to subjects intramuscular 2 times with 4 weeks apart<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events | Number of Participants with Treatment Emergent Adverse Events | 85 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunoglobulin(Ig)G Antibody Concentration | Adjusted geometric mean concentration (GMC) | Day 85 | 
| Fold Change in Antibody Concentration | Geometric mean fold change in antibody concentration from Day 1 to Day 85 for each group. | Day 1 to Day 85 | 
| Seroconversion Rate | 4-fold increase in Immunoglobulin(Ig)G antibody concentration | Day 85 | 
| Number of Participants With an Immune Response to First and Second Doses | Number of participants with Immunoglobulin(Ig)G antibody concentration above thresholds | Day 29 and Day 85 |