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

Hiv Clinical Trial

— MENPI  

Official title:

Safety and Immunogenicity Following Meningococcal and Pneumococcal Immunization Among Adult People Living With HIV: A Single Center, Non-blinded, Randomized Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04875819
• Other study ID #: H-19001166
• Secondary ID: 2020-000863-22
• Status: Recruiting
• Phase: Phase 4
• Start date: April 28, 2021
• Est. completion date: December 2026

Study information

• Verified date: May 2021
• Source: Hvidovre University Hospital
• Contact: Michaela Tinggaard, M.D.
• Phone: 22326800
• Email: michaela.tinggaard[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 55
• Est. completion date: December 2026
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years

• Seropositive for HIV-1

• Recipient of ART

• Plasma HIV-RNA < 500 copies/ml

• Patients written consent obtained

Exclusion Criteria:

• Pregnancy or breastfeeding

• History of meningococcal or pneumococcal vaccination

• Allergies towards any of the vaccine components

• Temperature > 38 ?C

• 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.)

Related Conditions & MeSH terms

• Communicable Diseases
• Hiv
• Infection
• Meningococcal Infections
• Pneumococcal Infections

Intervention

Drug:
• Neisseria meningitidis oligosaccharide conjugate vaccine and recombinant protein-based vaccine
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.
• 13 valent pneumococcal conjugate vaccine and 23 valent pneumococcal polysaccharide vaccine
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.

Locations

Country	Name	City	State
Denmark	Hvidovre Hospital	Hvidovre

Sponsors (1)

Lead Sponsor	Collaborator
Thomas Benfield

Country where clinical trial is conducted

Denmark, 

References & Publications (10)

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Pedersen RH, Lohse N, Østergaard L, Søgaard 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. Review. — View Citation

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. — View Citation

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. — View Citation

Søgaard OS, Schønheyder 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Number of participants with immediate adverse events		30 minutes post-vaccination
Secondary	Number of participants with short term adverse events		Day 5 post vaccination
Secondary	Number of participants with long term adverse events		Day 90 post-vaccination
Secondary	Streptococcus pneumoniae carriage rates	Proportion of study subject with a culture or PCR positive pharyngeal swab sample	Baseline and day 30 post-vaccination
Secondary	Neisseria meningitidis carriage rates	Proportion of study subject with a culture or PCR positive pharyngeal swab sample	Baseline and day 30 post-vaccination