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

Phase 1

Completed

• Conditions: Group B Streptococcal Infections
• Interventions: Biological: Placebo; Biological: GBS-NN/NN2

• Registration Number: NCT05782179
• Lead Sponsor: Minervax ApS

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2023-02-23
• Study Start: 2023-03-01
• Study First Submitted QC: 2023-03-21
• Study First Posted: 2023-03-23
• Primary Completion: 2023-12-14
• Status Verified: 2024-05
• Study Completion: 2024-05-23
• Last Update Submitted: 2024-05-27
• Last Update Posted: 2024-05-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

1. Participants aged 55 to 75 years.
2. 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.
3. Able to voluntarily provide written informed consent to participate in the study.
4. Female participants must be post-menopausal.
5. Participants capable and willing to follow trial schedule and procedures.

Exclusion Criteria

1. Participants who have received a GBS vaccine previously.

2. 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.

3. Laboratory values at screening which are deemed by the investigator to be clinically significantly abnormal.

4. Current or history of drug or alcohol abuse per investigator judgement.

5. Positive for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.

6. Participants currently participating in a clinical trial.

7. Participants receiving an investigational drug, vaccine or device during the 90 days preceding the initial dose in this study.

8. Any significant illness during the 4 weeks preceding the vaccination visit, per investigator judgement.

9. Participants with a history of severe allergic reactions after previous vaccination.

10. 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.

11. Participants receiving immunosuppressive therapy or immunoglobulins in the 6 months prior to screening.

12. 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.

13. Participants who have received antipyretics/analgesics treatment within 72 hours prior to dosing.

14. 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.

15. Participants with skin defects and/or tattoos at the proposed site of vaccine administration.

16. Donation of blood or blood products within 90 days prior to first study vaccination.

17. Participants who, in the opinion of the Investigator, are unsuitable for participation in the study.

18. 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]).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1 - Placebo	Placebo	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).
Cohort 1 - Active	GBS-NN/NN2	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).
Cohort 2 - Placebo	Placebo	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).
Cohort 3 - Active	GBS-NN/NN2	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).
Cohort 2 - Active	GBS-NN/NN2	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).
Cohort 4 - Placebo	Placebo	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).
Cohort 3 - Placebo	Placebo	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).
Cohort 4 - Active	GBS-NN/NN2	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).

Primary Outcome Measures

Name	Time	Method
Safety and tolerability of GBS-NN/NN2 vaccine	Up to 28 days after each vaccination	* 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.

Secondary Outcome Measures

Name	Time	Method
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.	4 weeks after each vaccination	Geometric mean fold increase in antibody concentration for antibodies to the four individual Alps
To evaluate the immune response up to 6 months following the third dose	Up to day 197	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
To assess whether pre existing antibody levels affect the vaccine-induced antibody response.	Up to 6 months after last vaccination	Seroconversion rate (proportion of participants with a 4-fold increase above baseline - pre dose concentration) at any time post vaccination.
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)	Up to day 365	* 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.
To evaluate IgG antibody response to the GBS-NN/NN2 vaccine at Day 197	Day 197	Geometric mean antibody concentration in μg/mL for antibodies to the four individual Alps

Trial Locations

Locations (1)

University Hospital Ghent - Centrum voor Vaccinologie (CEVAC) department; 🇧🇪 Ghent, Belgium