Safety and Immunogenicity Following Meningococcal and Pneumococcal Immunization Among Adult People Living With HIV

NCT04875819 | Recruiting Phase 4

• 2 other identifiers: H-190011662020-000863-22
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

MENPI is an investigator-initiated single-centre randomized controlled trial which aims to assess the efficacy and safety of meningococcal and pneumococcal vaccination in adults living with HIV receiving antiretroviral treatment. Participants are randomized 1:1 to either a two-dose Menveo® and Bexsero® regimen or a Prevenar13®/Pneumovax23® prime-boost regimen at day 0 and day 60 and cross over on day 90. All participants will follow an identical follow up program including plasma collection, pharyngeal swab, and adverse event registration. Immunogenicity will be determined on venous blood sampled at 30 days post-vaccination and yearly for five years.

Conditions

Hiv; Meningococcal Infections; Pneumococcal Infections

Outcome Measures

Primary Outcomes (3)

• Change in immunogenic response from baseline, Menveo

  A ≥4-fold rise in rabbit complement source (rSBA) for the four serogroups A, C, Y, and W-135. Seroprotection is defined as an rSBA titre ≥1:8 and patients will be classified as previously immune if baseline rSBA is ≥1:8.

  Day 30 and year 1, 2, 3, 4, and 5 post-vaccination

• Change in immunogenic response from baseline, Bexsero

  A ≥4-fold rise in antibody titers against a panel of four meningococcal serogroup B reference strains between pre-vaccination and post-vaccination timepoints, or a post-vaccination antibody titre ratio of ≥1:4 for individuals who were seronegative before vaccination.

  Day 30 and year 1, 2, 3, 4, and 5 post-vaccination

• Change in immunogenic response from baseline, Prevenar13/Pneumovax23

  A ≥2-fold rise in serum anti-capsular IgG GMC for 12 shared pneumococcal polysaccharides (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F)

  Day 30 and year 1, 2, 3, 4, and 5 post-vaccination

Secondary Outcomes (5)

• Number of participants with immediate adverse events

  30 minutes post-vaccination

• Number of participants with short term adverse events

  Day 5 post vaccination

• Number of participants with long term adverse events

  Day 90 post-vaccination

• Streptococcus pneumoniae carriage rates

  Baseline and day 30 post-vaccination

• Neisseria meningitidis carriage rates

  Baseline and day 30 post-vaccination

Study Arms (2)

Menveo + Bexsero

EXPERIMENTAL

Drug: Neisseria meningitidis oligosaccharide conjugate vaccine and recombinant protein-based vaccine

Prevenar13 + Pneumovax23

EXPERIMENTAL

Drug: 13 valent pneumococcal conjugate vaccine and 23 valent pneumococcal polysaccharide vaccine

Interventions

Neisseria meningitidis oligosaccharide conjugate vaccine and recombinant protein-based vaccine DRUG

One dose (0.5 ml) of conjugate vaccine against meningococcal serogroups ACWY (Menveo®) and one dose of a recombinant protein-based vaccine against meningococcal serogroup B (Bexsero®) at day 0 followed by another dose (0.5 ml) of each vaccine at day 60.

Also known as: Menveo® and Bexsero®

Menveo + Bexsero

13 valent pneumococcal conjugate vaccine and 23 valent pneumococcal polysaccharide vaccine DRUG

One dose (0.5 ml) of pneumococcal conjugate vaccine (Prevenar13®) at day 0 and one dose (0.5 ml) of pneumococcal polysaccharide vaccine (Pneumovax23®) at day 60.

Also known as: Prevenar13® and Pneumovax23®

Prevenar13 + Pneumovax23

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Seropositive for HIV-1
• Recipient of ART
• Plasma HIV-RNA \< 500 copies/ml
• Patients written consent obtained

You may not qualify if:

• Pregnancy or breastfeeding
• History of meningococcal or pneumococcal vaccination
• Allergies towards any of the vaccine components
• Temperature \> 38 ᵒC
• Sign of bacterial infection
• Previous known or suspected disease caused by N. meningitidis
• Active AIDS associated illness
• Active malignancy
• End-stage renal or liver disease
• Bleeding disorder
• Recipient of any blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation within the last month
• Use of immunosuppressive agents (corticosteroids, cancer chemotherapeutic agents etc.)

Sponsors & Collaborators

• Thomas Benfield: lead

Study Sites (1)

Hvidovre Hospital

Hvidovre, 2650, Denmark

RECRUITING

Related Publications (10)

• 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.

  PMID: 24166695 BACKGROUND

• 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.

  PMID: 26654248 BACKGROUND

• Harboe ZB, Larsen MV, Ladelund S, Kronborg G, Konradsen HB, Gerstoft J, Larsen CS, Pedersen C, Pedersen G, Obel N, Benfield T. Incidence and risk factors for invasive pneumococcal disease in HIV-infected and non-HIV-infected individuals before and after the introduction of combination antiretroviral therapy: persistent high risk among HIV-infected injecting drug users. Clin Infect Dis. 2014 Oct 15;59(8):1168-76. doi: 10.1093/cid/ciu558. Epub 2014 Jul 17.

  PMID: 25038114 BACKGROUND

• MacNeil JR, Rubin LG, Patton M, Ortega-Sanchez IR, Martin SW. Recommendations for Use of Meningococcal Conjugate Vaccines in HIV-Infected Persons - Advisory Committee on Immunization Practices, 2016. MMWR Morb Mortal Wkly Rep. 2016 Nov 4;65(43):1189-1194. doi: 10.15585/mmwr.mm6543a3.

  PMID: 27811836 BACKGROUND

• 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.

  PMID: 22622049 BACKGROUND

• Frota ACC, Ferreira B, Harrison LH, Pereira GS, Pereira-Manfro W, Machado ES, de Oliveira RH, Abreu TF, Milagres LG, Hofer CB. Safety and immune response after two-dose meningococcal C conjugate immunization in HIV-infected children and adolescents in Rio de Janeiro, Brazil. Vaccine. 2017 Dec 15;35(50):7042-7048. doi: 10.1016/j.vaccine.2017.10.043. Epub 2017 Oct 31.

  PMID: 29100708 BACKGROUND

• Pedersen RH, Lohse N, Ostergaard L, Sogaard OS. The effectiveness of pneumococcal polysaccharide vaccination in HIV-infected adults: a systematic review. HIV Med. 2011 Jul;12(6):323-33. doi: 10.1111/j.1468-1293.2010.00892.x. Epub 2010 Nov 8.

  PMID: 21059168 BACKGROUND

• Lee KY, Tsai MS, Kuo KC, Tsai JC, Sun HY, Cheng AC, Chang SY, Lee CH, Hung CC. Pneumococcal vaccination among HIV-infected adult patients in the era of combination antiretroviral therapy. Hum Vaccin Immunother. 2014;10(12):3700-10. doi: 10.4161/hv.32247.

  PMID: 25483681 BACKGROUND

• Sogaard OS, Schonheyder HC, Bukh AR, Harboe ZB, Rasmussen TA, Ostergaard L, Lohse N. Pneumococcal conjugate vaccination in persons with HIV: the effect of highly active antiretroviral therapy. AIDS. 2010 Jun 1;24(9):1315-22. doi: 10.1097/QAD.0b013e328339fe0b.

  PMID: 20559037 BACKGROUND

• Rodriguez-Barradas MC, Serpa JA, Munjal I, Mendoza D, Rueda AM, Mushtaq M, Pirofski LA. Quantitative and Qualitative Antibody Responses to Immunization With the Pneumococcal Polysaccharide Vaccine in HIV-Infected Patients After Initiation of Antiretroviral Treatment: Results From a Randomized Clinical Trial. J Infect Dis. 2015 Jun 1;211(11):1703-11. doi: 10.1093/infdis/jiu819. Epub 2014 Dec 23.

  PMID: 25538270 BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Meningococcal Infections; Pneumococcal Infections

Interventions

Meningococcal Vaccines; 4CMenB vaccine; 13-valent pneumococcal vaccine

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Neisseriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections

Intervention Hierarchy (Ancestors)

Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Michaela Tinggaard, M.D.

  Department of Infectious Diseases, Hvidovre Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michaela Tinggaard, M.D.

CONTACT

22326800; michaela.tinggaard@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical professor

Study Record Dates

• First Submitted: April 12, 2021
• First Posted: May 6, 2021
• Study Start: April 28, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 6, 2021

Record last verified: 2021-05

Locations

DK (1)