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

• ClinicalTrials.gov Identifier: NCT03682939
• Recruitment Status: Unknown
• First Posted: September 25, 2018
• Last Update Posted: April 10, 2019
• Sponsor: St George's, University of London
• Information provided by (Responsible Party): St George's, University of London

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hiv; Meningitis, Meningococcal; HIV Infections	Biological: Bexsero® (meningitis B vaccine); Biological: Menveo® (meningitis ACWY vaccine)	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 55 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Evaluation of Safety and Immunogenicity of Meningococcal B and Meningococcal ACWY Vaccine in at Risk Population (ProPositive Study)
• Actual Study Start Date: February 21, 2019
• Estimated Primary Completion Date: June 2020
• Estimated Study Completion Date: March 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: Day 0 (baseline) and Day 60 ]
   The human complement serum bactericidal assay (hSBA) mean titres against relevant strains of meningococcal B at baseline and one month after completion of vaccination.
2. The proportion of participants who achieve at least a four fold increase in hSBA titres. [ Time Frame: Day 60 ]
   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.
3. The proportion of participants who achieve a 'protective' hSBA titre of >1:4 after two doses of Bexsero [ Time Frame: Day 60 ]
   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.

Secondary Outcome Measures :

1. 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 [ Time Frame: Day 7 after vaccines 1 and 2 ]

   We will assess the following:

   1. The incidence of subjects with solicited local and systemic AEs up to 7 days (including the day of vaccination) after Visits 1 and 2.
   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.
   3. The incidence of subjects with SAEs and AEs leading to withdrawal throughout the study period.
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 [ Time Frame: Day 60 ]
   We will measure rSBA GMTs for MenACWY antigens at baseline and Visit3.
3. The proportion of subjects with at least a four fold change in rSBA from baseline to 30 days after the second vaccine [ Time Frame: Day 0 and Day 60 ]
   The proportion of subjects with at least 4 fold increase in rSBA against relevant MenACWY serogroups from baseline to Visit3.
4. The proportion of subjects with "protective" rSBA titres >1:8 against relevant MenACWY serogroups after two doses of Menveo [ Time Frame: Day 60 ]
   The proportion of subjects with "protective" rSBA titres >1:8 against relevant MenACWY serogroups at Visit3.

Eligibility Criteria

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

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

Contacts and Locations

Contacts

Contact: Catherine Cosgrove, MBBS PhD MRCP; +44(0)2087252316; ccosgrov@sgul.ac.uk

Contact: Catherine Isitt, MBChB MRCP; +44(0)2087252316; cisitt@sgul.ac.uk

Locations

United Kingdom

St Georges University Hospital; Recruiting

London, United Kingdom, SW17 0RE

Contact: Catheirne E Isitt, MBChB 02087252316 vaccine@sgul.ac.uk

Sponsors and Collaborators

St George's, University of London

Investigators

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

More Information

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.

• Responsible Party: St George's, University of London
• ClinicalTrials.gov Identifier: NCT03682939
• Other Study ID Numbers: 17.0177
• First Posted: September 25, 2018
• Last Update Posted: April 10, 2019
• Last Verified: April 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by St George's, University of London:

vaccination; HIV; meningitis; Vaccine; Immunogenicity; Safety; Bexsero; Menveo; co-administration

Additional relevant MeSH terms:

Meningitis, Meningococcal; Meningitis; Infections; Central Nervous System Diseases; Nervous System Diseases; Meningitis, Bacterial; Central Nervous System Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Meningococcal Infections; Neisseriaceae Infections; Gram-Negative Bacterial Infections; Central Nervous System Infections; Vaccines; Immunologic Factors; Physiological Effects of Drugs