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

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

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.

Study Overview

• Status: Unknown
• Conditions: HIV Infections; Hiv; Meningitis, Meningococcal
• Intervention / Treatment: Biological: Bexsero® (meningitis B vaccine); Biological: Menveo® (meningitis ACWY vaccine)

• Study Type: Interventional
• Enrollment (Anticipated): 55
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Catherine Cosgrove, MBBS PhD MRCP; Phone Number: +44(0)2087252316; Email: ccosgrov@sgul.ac.uk
• Study Contact Backup: Name: Catherine Isitt, MBChB MRCP; Phone Number: +44(0)2087252316; Email: cisitt@sgul.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, SW17 0RE
    • Recruiting
    • St Georges University Hospital
    • Contact: Catheirne E Isitt, MBChB; Phone Number: 02087252316; Email: vaccine@sgul.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: St George's, University of London
• Investigators: Principal Investigator: Catherine Cosgrove, MBBS PhD, St George's, University of London

Publications and helpful links

General Publications

• Simmons RD, Kirwan P, Beebeejaun K, Riordan A, Borrow R, Ramsay ME, Delpech V, Lattimore S, Ladhani S. Risk of invasive meningococcal disease in children and adults with HIV in England: a population-based cohort study. BMC Med. 2015 Dec 9;13:297. doi: 10.1186/s12916-015-0538-6.
• Dwilow R, Fanella S. Invasive meningococcal disease in the 21st century-an update for the clinician. Curr Neurol Neurosci Rep. 2015 Mar;15(3):2. doi: 10.1007/s11910-015-0524-6.
• Miller L, Arakaki L, Ramautar A, Bodach S, Braunstein SL, Kennedy J, Steiner-Sichel L, Ngai S, Shepard C, Weiss D. Elevated risk for invasive meningococcal disease among persons with HIV. Ann Intern Med. 2014 Jan 7;160(1):30-7. doi: 10.7326/0003-4819-160-1-201401070-00731.
• Cohen C, Singh E, Wu HM, Martin S, de Gouveia L, Klugman KP, Meiring S, Govender N, von Gottberg A; Group for Enteric, Respiratory and Meningeal disease Surveillance in South Africa (GERMS-SA). Increased incidence of meningococcal disease in HIV-infected individuals associated with higher case-fatality ratios in South Africa. AIDS. 2010 Jun 1;24(9):1351-60. doi: 10.1097/QAD.0b013e32833a2520.
• Cohn AC, MacNeil JR, Clark TA, Ortega-Sanchez IR, Briere EZ, Meissner HC, Baker CJ, Messonnier NE; Centers for Disease Control and Prevention (CDC). Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2013 Mar 22;62(RR-2):1-28.
• Frota AC, Milagres LG, Harrison LH, Ferreira B, Menna Barreto D, Pereira GS, Cruz AC, Pereira-Manfro W, de Oliveira RH, Abreu TF, Hofer CB. Immunogenicity and safety of meningococcal C conjugate vaccine in children and adolescents infected and uninfected with HIV in Rio de Janeiro, Brazil. Pediatr Infect Dis J. 2015 May;34(5):e113-8. doi: 10.1097/INF.0000000000000630.
• Lujan-Zilbermann J, Warshaw MG, Williams PL, Spector SA, Decker MD, Abzug MJ, Heckman B, Manzella A, Kabat B, Jean-Philippe P, Nachman S, Siberry GK; International Maternal Pediatric Adolescent AIDS Clinical Trials Group P1065 Protocol Team. Immunogenicity and safety of 1 vs 2 doses of quadrivalent meningococcal conjugate vaccine in youth infected with human immunodeficiency virus. J Pediatr. 2012 Oct;161(4):676-81.e2. doi: 10.1016/j.jpeds.2012.04.005. Epub 2012 May 22.
• Findlow J, Bai X, Findlow H, Newton E, Kaczmarski E, Miller E, Borrow R. Safety and immunogenicity of a four-component meningococcal group B vaccine (4CMenB) and a quadrivalent meningococcal group ACWY conjugate vaccine administered concomitantly in healthy laboratory workers. Vaccine. 2015 Jun 26;33(29):3322-30. doi: 10.1016/j.vaccine.2015.05.027. Epub 2015 May 27.
• Santolaya ME, O'Ryan ML, Valenzuela MT, Prado V, Vergara R, Munoz A, Toneatto D, Grana G, Wang H, Clemens R, Dull PM; V72P10 Meningococcal B Adolescent Vaccine Study group. Immunogenicity and tolerability of a multicomponent meningococcal serogroup B (4CMenB) vaccine in healthy adolescents in Chile: a phase 2b/3 randomised, observer-blind, placebo-controlled study. Lancet. 2012 Feb 18;379(9816):617-24. doi: 10.1016/S0140-6736(11)61713-3. Epub 2012 Jan 18. Erratum In: Lancet. 2015 May 2;385(9979):1728.

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2019
• Primary Completion (Anticipated): June 1, 2020
• Study Completion (Anticipated): March 1, 2021

Study Registration Dates

• First Submitted: September 13, 2018
• First Submitted That Met QC Criteria: September 20, 2018
• First Posted (Actual): September 25, 2018

Study Record Updates

• Last Update Posted (Actual): April 10, 2019
• Last Update Submitted That Met QC Criteria: April 8, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Safety; HIV; Vaccine; Immunogenicity; meningitis; vaccination; Bexsero; Menveo; co-administration
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Central Nervous System Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Meningitis, Bacterial; Central Nervous System Bacterial Infections; Meningococcal Infections; Neisseriaceae Infections; Meningitis, Meningococcal; Meningitis; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 17.0177

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No