Evaluation of Safety and Immunogenicity of Meningococcal B and Meningococcal ACWY Vaccine in at Risk Population

Study Overview
=================
Brief Summary
-----------------
This study aims to evaluate the immunogenicity, safety and tolerability of co-administration of vaccinations for meningitis B (Bexsero®) and meningitis ACWY (Menveo®) in adults and children aged 10-45 years living with HIV. All participants will be vaccinated with both Menveo® and Bexsero® on days 0 and 30. Immunogenicity will be determined on venous blood sampled at days 0 and 60. Adverse effects will be recorded to evaluate safety.

Official Title
-----------------
Evaluation of Safety and Immunogenicity of Meningococcal B and Meningococcal ACWY Vaccine in at Risk Population (ProPositive Study)

Conditions
-----------------
Hiv, Meningitis, Meningococcal, HIV Infections

Intervention / Treatment
-----------------
* Biological: Bexsero® (meningitis B vaccine)
* Biological: Menveo® (meningitis ACWY vaccine)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Any 10-45-year old male or female patients with confirmed HIV infection where they (or someone with parental responsibility) can sign fully informed consent and are able to comply with study requirements. Exclusion Criteria: Pregnancy or breast feeding, History of MenACWY (Menveo® or Nimenrix®) and 4CMenB (Bexsero®) vaccination in the previous 2 years, Receipt of other non-live vaccines within 2 weeks and live vaccines within 4 weeks of first dose, planned receipt of vaccine within 2 weeks of study visits, Current active malignancy, Known latex allergy Known or suspected hypersensitivity to any components of the vaccines or history of severe allergic reaction after previous vaccination Bleeding disorder preventing IM vaccination, Any acute or chronic illness which according to the investigators judgement would prevent patients to receive the vaccines or participate in the study Participation in clinical trials concerning investigational medical product within 0 days or before completion of the study Children in care

Ages Eligible for Study
-----------------
Minimum Age: 10 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm<br>Single arm, open-label, all participants will receive both Bexsero® (meningitis B vaccine) and Menveo® (meningitis ACWY vaccine) vaccines. | Biological: Bexsero® (meningitis B vaccine)<br>* Bexsero® 0.5ml IM vaccine administered into non-dominant arm of participant<br>Biological: Menveo® (meningitis ACWY vaccine)<br>* Menveo® 0.5ml IM vaccine administered into dominant arm of participant<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hSBA geometric mean titres to relevant strains of meningococcal B following two doses of the 4CmenB vaccine (Bexsero®) in people living with HIV | The human complement serum bactericidal assay (hSBA) mean titres against relevant strains of meningococcal B at baseline and one month after completion of vaccination. | Day 0 (baseline) and Day 60 | 
| The proportion of participants who achieve at least a four fold increase in hSBA titres. | Blood will be taken one month after the second vaccine and serum tested for hSBA titres. The proportion of participants who achieve at least a four fold increase in hSBA titres will be calculated. | Day 60 | 
| The proportion of participants who achieve a 'protective' hSBA titre of >1:4 after two doses of Bexsero | Blood will be taken one month after the second vaccine and serum tested for hSBA titres. The proportion of participants who are deemed to have protective titres >1:4 will be calculated. | Day 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of solicited and unsolicited adverse and serious adverse events after two doses of MenACWY (Menveo®) and 4CMenB (Bexsero®) vaccines when co-administered in people living with HIV | We will assess the following: The incidence of subjects with solicited local and systemic AEs up to 7 days (including the day of vaccination) after Visits 1 and 2. The incidence of subjects with any other (unsolicited) AEs, including any SAEs, AEs leading to withdrawal and medically attended AEs up to 7 days (including the day of vaccination) after Visits 1 and 2. The incidence of subjects with SAEs and AEs leading to withdrawal throughout the study period. | Day 7 after vaccines 1 and 2 | 
| The geometric mean titres to Meningococcal ACWY antigens after two doses of the MenACWY (Menveo®) vaccine in people with HIV at one month after the second vaccination | We will measure rSBA GMTs for MenACWY antigens at baseline and Visit3. | Day 60 | 
| The proportion of subjects with at least a four fold change in rSBA from baseline to 30 days after the second vaccine | The proportion of subjects with at least 4 fold increase in rSBA against relevant MenACWY serogroups from baseline to Visit3. | Day 0 and Day 60 | 
| The proportion of subjects with protective rSBA titres >1:8 against relevant MenACWY serogroups after two doses of Menveo | The proportion of subjects with protective rSBA titres >1:8 against relevant MenACWY serogroups at Visit3. | Day 60 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
vaccination, HIV, meningitis, Vaccine, Immunogenicity, Safety, Bexsero, Menveo, co-administration