Study to Evaluate the Safety, Tolerability and Immunogenicity of Three Doses of GBS Vaccine in Elderly Participants

Study Overview
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Brief Summary
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The study is a randomised, double-blind, placebo-controlled, parallel group study to evaluate the safety, tolerability and immunogenicity of three doses of GBS NN/NN2 with Alhydrogel® (Recombinant protein vaccine against Group B Streptococcus) in elderly participants aged 55 to 75.Participants will be followed up to 6 months after last vaccination.

Detailed Description
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Sixty (60) healthy older adult participants aged 55 to 75 years will be randomised in two cohorts; 30 obese and/or diabetic participants aged 55 to 75 years will be randomised in two cohorts. Participants will be involved in the study for approximately one year including screening and safety follow-up. Eligible participants will be administered a dose of GBS-NN/NN2 or placebo on three occasions: the first dose will be administered on Day 1, followed by the second and third doses 4 and 24 weeks later, respectively.

Official Title
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A Randomised, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Safety, Tolerability and Immunogenicity of Three Doses of Group B Streptococcus Vaccine (GBS NN/NN2 With Alhydrogel®) in Elderly Participants Aged 55 to 75

Conditions
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Group B Streptococcal Infections

Intervention / Treatment
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* Biological: GBS-NN/NN2
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants aged 55 to 75 years. Body mass index (BMI) ≥18 and ≤30 kg/m2 for healthy participants, ≥ 30 to ≤45 kg/m2 for obese participants and ≥18 to ≤45 kg/m2 for type 2 diabetic participants. Able to voluntarily provide written informed consent to participate in the study. Female participants must be post-menopausal. Participants capable and willing to follow trial schedule and procedures. Exclusion Criteria: Participants who have received a GBS vaccine previously. Participants with history or presence of significant (as evaluated by the investigator) cardiovascular disease, pulmonary, hepatic, gallbladder or biliary tract, renal, haematological, gastrointestinal, endocrine, immunologic, dermatological, neurological, psychiatric, autoimmune disease or current infection. NOTE: Patients with type 2 diabetes are to be recruited for Cohort 3 and Cohort 4. Laboratory values at screening which are deemed by the investigator to be clinically significantly abnormal. Current or history of drug or alcohol abuse per investigator judgement. Positive for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. Participants currently participating in a clinical trial. Participants receiving an investigational drug, vaccine or device during the 90 days preceding the initial dose in this study. Any significant illness during the 4 weeks preceding the vaccination visit, per investigator judgement. Participants with a history of severe allergic reactions after previous vaccination. Participants who have received any vaccine within 30 days of first IMP administration, or who are planning to receive any vaccine (eg, travel vaccines) up to 30 days after each vaccination. NOTE: Exceptions could be made for emergency vaccinations (eg, tetanus) or vaccination campaigns (eg, SARS, CoV-2 or influenza) which will be permitted not less than 7 days before or after study vaccination. Participants receiving immunosuppressive therapy or immunoglobulins in the 6 months prior to screening. Participants within a 7-day period after an acute infection in the 7 days preceding vaccination, as per investigator judgement, or with fever (oral temperature >37.9°C) in the 72 hours preceding vaccination. Participants who have received antipyretics/analgesics treatment within 72 hours prior to dosing. Participants on chronic medications that are likely to affect the assessments specified in the protocol (eg, anticoagulant therapy, systemic steroids). NOTE: Chronic medications such as antihypertensives, bronchodilators, statins that do not affect the immune system, will be permitted and allowed to continue during the study at the discretion of the investigator. Treatment for diabetes will be continued as required for the diabetic participants recruited. Non-steroidal anti-inflammatory drugs or paracetamol will be permitted for the treatment of headache or other symptoms during the study. Use of over the counter (OTC) vitamins and dietary supplements is allowed. Participants with skin defects and/or tattoos at the proposed site of vaccine administration. Donation of blood or blood products within 90 days prior to first study vaccination. Participants who, in the opinion of the Investigator, are unsuitable for participation in the study. Involvement in the planning and/or conduct of the study (applies to both Sponsor personnel and/or personnel at the study centre or Clinical Research Organisation [CRO]).

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 75 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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 - Active<br>Cohort 1 (30 healthy older adult) will receive three injections, each consisting of 50 μg of GBS-NN and 50 μg of GBS NN2 bound to aluminium hydroxide in a 4:1 ratio (investigational medicinal product or placebo). | Biological: GBS-NN/NN2<br>* GBS-NN/NN2 bound to alhydrogel as an adjuvant<br>|
| Placebo Comparator: Cohort 1 - Placebo<br>Cohort 1 (30 healthy older adult) will receive three injections, each consisting of 50 μg of GBS-NN and 50 μg of GBS NN2 bound to aluminium hydroxide in a 4:1 ratio (investigational medicinal product or placebo). | Biological: Placebo<br>* Normal Saline 0.9 %<br>|
| Experimental: Cohort 2 - Active<br>Cohort 2 (30 healthy older adult) will receive three injections, each consisting of 125 μg of GBS-NN and 125 μg of GBS NN2 bound to aluminium hydroxide in a 4:1 ratio (investigational medicinal product or placebo). | Biological: GBS-NN/NN2<br>* GBS-NN/NN2 bound to alhydrogel as an adjuvant<br>|
| Placebo Comparator: Cohort 2 - Placebo<br>Cohort 2 (30 healthy older adult) will receive three injections, each consisting of 125 μg of GBS-NN and 125 μg of GBS NN2 bound to aluminium hydroxide in a 4:1 ratio (investigational medicinal product or placebo). | Biological: Placebo<br>* Normal Saline 0.9 %<br>|
| Experimental: Cohort 3 - Active<br>Cohort 3 (15 obese and/or diabetic older adults) will receive three injections, each consisting of 50 μg of GBS-NN and 50 μg of GBS NN2 bound to aluminium hydroxide in a 4:1 ratio (investigational medicinal product or placebo). | Biological: GBS-NN/NN2<br>* GBS-NN/NN2 bound to alhydrogel as an adjuvant<br>|
| Placebo Comparator: Cohort 3 - Placebo<br>Cohort 3 (15 obese and/or diabetic older adults) will receive three injections, each consisting of 50 μg of GBS-NN and 50 μg of GBS NN2 bound to aluminium hydroxide in a 4:1 ratio (investigational medicinal product or placebo). | Biological: Placebo<br>* Normal Saline 0.9 %<br>|
| Experimental: Cohort 4 - Active<br>Cohort 4 (15 obese and/or diabetic older adults) will receive three injections, each consisting of 125 μg of GBS-NN and 125 μg of GBS NN2 bound to aluminium hydroxide in a 4:1 ratio (investigational medicinal product or placebo). | Biological: GBS-NN/NN2<br>* GBS-NN/NN2 bound to alhydrogel as an adjuvant<br>|
| Placebo Comparator: Cohort 4 - Placebo<br>Cohort 4 (15 obese and/or diabetic older adults) will receive three injections, each consisting of 125 μg of GBS-NN and 125 μg of GBS NN2 bound to aluminium hydroxide in a 4:1 ratio (investigational medicinal product or placebo). | Biological: Placebo<br>* Normal Saline 0.9 %<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of GBS-NN/NN2 vaccine | Safety and tolerability as determined by the occurrence of AEs consisting of local and systemic reactogenicity within 7 days after vaccination Unsolicited AEs, including AESIs, MAAEs and SAEs within 28 days after each vaccination AESIs, MAAEs, ARs/SARs leading to withdrawal from the study. | Up to 28 days after each vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate IgG antibody response to the GBS-NN/NN2 vaccine at Day 197 | Geometric mean antibody concentration in μg/mL for antibodies to the four individual Alps | Day 197 | 
| To evaluate IgG antibody responses induced by the three vaccine doses, on a 0-, 1- and 6-month regimen, in older adult participants 4 weeks after each vaccination. | Geometric mean fold increase in antibody concentration for antibodies to the four individual Alps | 4 weeks after each vaccination | 
| To assess whether pre existing antibody levels affect the vaccine-induced antibody response. | Seroconversion rate (proportion of participants with a 4-fold increase above baseline - pre dose concentration) at any time post vaccination. | Up to 6 months after last vaccination | 
| To evaluate the immune response up to 6 months following the third dose | Proportion of participants achieving antibody concentrations for antibodies to the four individual Alps (Alp 1, Alp2/3, Rib and AlpC) above specific thresholds at Days 29, 57, 169, and 197 | Up to day 197 | 
| To evaluate the long-term safety profile of the GBS-NN/NN2 vaccine between Day 57 (28 days post second injection) to Day 168 and 6 months following the third dose (safety endpoint) | Proportion of participants with any SAE from between Day 57 (28 days post second injection) to Day 168 and 28 days after third vaccination (Day 197) up to Day 365. Proportion of participants with MAAEs, AESIs, ARs/SARs requiring a medical consultation, and or leading to withdrawal from the study from 28 days after third vaccination (Day 197) up to Day 365. | Up to day 365 |