Safety and Immunogenicity of a Group B Streptococcus Vaccine in Non-pregnant Women 18-40 Years of Age.

Study Overview
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Brief Summary
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Part A: The primary objective is to evaluate the safety and tolerability of a potential vaccine against Group B streptococcus. Part B: To evaluate the long term safety profile of the GBS-NN vaccine up to one year following the first dose.

Detailed Description
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Part A: Subjects will receive 2 doses of the vaccine, GBS-NN, and will be followed for 12 weeks after the first dose of the vaccine. The following safety endpoints will be evaluated to support this objective: local and systemic reactogenicity; adverse events; laboratory tests; urinalysis; vital signs; 12-Lead ECG parameters; physical examination. In addition hereto, immunological parameters will be evaluated. Part B: Subjects will receive one or 2 doses of GBS-NN, and will be followed for 12 months after the first dose of the vaccine. The following safety endpoints will be evaluated to support this objective: local and systemic reactogenicity; adverse events; laboratory tests; urinalysis; vital signs; 12-Lead ECG parameters; physical examination. In addition hereto, immunological parameters will be evaluated.

Official Title
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A Two-part, Phase I, Randomised, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Safety, Tolerability and Immunogenicity of a Dose Range og Group B Streptococcus Vaccine in Healthy Female Volunteers Aged 18 to 40.

Conditions
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Infection by Streptococcus Group B

Intervention / Treatment
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* Biological: GBS-NN vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult female volunteers (as determined by medical history, physical examination, laboratory test values, vital signs and electrocardiograms [ECGs] at screening) aged 18 - 40 years. Body mass index (BMI) ≥ 18 and ≤ 30 kg/m2. Volunteers weight ≥ 50kg and ≤100kg at screening. Able to voluntarily provide written informed consent to participate in the study. Must understand the purposes and risks of the study and agree to follow the restrictions and schedule of procedures as defined in the protocol. Volunteers must be pre-menopausal. Volunteers who have had a hysterectomy will have pre-menopausal status confirmed by a FSH and oestradiol test. Females of childbearing potential must have a negative pregnancy test at screening (β HCG) and prior to each dose and must be willing to use an adequate and highly effective method of contraception until at least Day 85 of the study. A highly effective method of birth control is defined as one which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as sterilisation, implants, injectables, combined oral contraceptives, IUDs (Intrauterine Device), condoms, occlusive caps (cervical/vault caps) with spermicidal foam/gel/ film/cream/suppository. True sexual abstinence is acceptable when this is in line with the preferred and usual lifestyle of the volunteer (periodic abstinence e.g. calendar, ovulation, symptothermal, post-ovulation methods, declaration of abstinence for the duration of the trial, and withdrawal are not acceptable methods of contraception) In Part A: Volunteers must be non-smokers for at least 3 months prior to first studyvaccine administration. In Part B: Volunteers may be light smokers i.e. up to a maximum of 5 cigarettes per day or nicotine equivalent. Must be willing to consent to have data entered into The Over Volunteering Prevention System (TOPS). The volunteer's primary care physician has confirmed within the last 12 months that there is nothing in their medical history that would preclude their enrolment into a clinical trial. Exclusion Criteria: Volunteers 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 to be clinically significant, unless agreed in advance by the Sponsor's Responsible Medic and Principal Investigator. Current or history of drug or alcohol abuse, or a positive alcohol breath test prior to first dosing. 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). Volunteers with a history of severe allergic reactions after previous vaccination. Volunteers 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. Volunteers receiving immunosuppressive therapy (e.g. systemic steroids, cancer therapies, methotrexate, azathioprine) in the 6 months prior to screening, antibiotics within 10 days of receiving the first dose or taking any short-term medications including over-the-counter preparations, vitamins, herbal and/or mineral supplements 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. Volunteers with tattoos at the proposed site of vaccine administration. Donation of blood or blood products within 90 days prior to vaccine administration. Volunteers 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: GBS-NN Vaccine<br>GBS-NN vaccine administered either adsorbed to Alhydrogel® or alone. | Biological: GBS-NN vaccine<br>* Three dose levels will be administered, with and without Alhydrogel®<br>|
| Placebo Comparator: Sterile dilution buffer with Alhydrogel<br>The placebo will contain either Alhydrogel® or buffer alone. | Biological: GBS-NN vaccine<br>* Three dose levels will be administered, with and without Alhydrogel®<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A Number of Participants With Treatment Emergent Adverse Events | Number of Participants with Treatment Emergent Adverse Events | 12 weeks (to Day 85) | 
| Part B Number of Participants With Treatment Emergent Adverse Events | Number of Participants with Treatment Emergent Adverse Events | 12 weeks (to Day 85) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A Antibody Concentration | Geometric mean antibody concentration | 12 weeks (Day 85) | 
| Part B Antibody Concentration | Geometric mean antibody concentration | 12 weeks (Day 85) | 
| Part B Antibody Concentration | Geometric mean antibody concentration | 1 year (Day 365) | 
| Part B Number of Participants With Treatment Emergent Adverse Events | Number of Participants with Treatment Emergent Adverse Events | Day 85 to Day 365 |