V114-030

A Phase 3, Multicenter, Randomized, Double-blind, Active Comparator controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 Followed by Administration of PNEUMOVAX™23 Eight Weeks Later in Children Infected with Human Immunodeficiency Virus (HIV) (PNEU–WAY PED)

Rationale

Human immunodeficiency virus (HIV) infection leads to defects in the humoral and cellmediated immune systems of infected children. These children are then at an increased risk for infection with various microbial agents, including Streptococcus pneumoniae [Janoff, E.N., et al 1992] [Janoff, E. N., et al 1993] [Bliss, S. J., et al 2008] [Madhi, S. A., et al 2000][Madhi, S. A., et al 2000]. The incidence of invasive pneumococcal disease (IPD) is estimated to be 9- to 43-fold higher in HIV infected children as compared with HIV uninfected children and this burden is more apparent in resource-poor settings [Madhi, S. A.,et al 2000] [Madhi, S. A., et al 2001] [Peters, V. B., et al 1994] [Spector, S. A., et al 1994][Dankner, W. M., et al 2001] [Andiman, W. A., et al 1996] [Jones, N., et al 1998] [Nachman,S., et al 2005] [Laufer, M. K., et al 2006].

Routine PCV immunization of children is effective in preventing vaccine serotype-specific pneumococcal disease, including in HIV infected children, where it has been shown to decrease the risk of IPD [Centers for Disease Control and Prevention 2005] [Whitney, C. G.,et al 2003]. Given the high morbidity and mortality associated with IPD, immunization guidelines recommend that children and adolescents infected with HIV who have not been vaccinated with the 13-valent Prevnar 13™ vaccine, receive a catch-up dose of Prevnar 13™.

These guidelines also recommend that children infected with HIV receive the 23-valent pneumococcal polysaccharide (PnPs) vaccine, PNEUMOVAX™23, at least 8 weeks after receiving PCV, followed by another dose of PNEUMOVAX™23 not less than 5 years later [Bliss, S. J., et al 2008] [Robinson, C. L., et al 2018] [Centers for Disease Control and Prevention (CDC) 2013] [National Center for Immunization and Respiratory Diseases 2018].

Despite the commercial availability of pneumococcal vaccines, pneumococcal disease remains an important worldwide concern due to lack of universal availability of vaccines and due to the emergence of non-vaccine serotypes. V114 contains all the pneumococcal serotypes contained in Prevnar 13™ plus 2 additional serotypes (22F, 33F), which have emerged as important causes of IPD. This clinical study is designed to evaluate the safety, tolerability, and immunogenicity of V114 in children (6 to 17 years of age inclusive) infected with HIV (CD4+ T-cell count ≥200 cells/μL and a plasma HIV ribonucleic acid [RNA] value <50,000 copies/mL tested at Screening). In comparison to Prevnar 13™, V114 has the potential to provide comparable protection against pneumococcal disease caused by the serotypes in common between the 2 vaccines and offer additional protection against IPD caused by the 2 PnPs serotypes (22F and 33F) not contained in Prevnar 13™.

Primary Objectives

• To evaluate the safety and tolerability of V114 with respect to the proportion of participants with adverse events (AEs).

• To evaluate the anti-pneumococcal polysaccharide (PnPs)serotype-specific Immunoglobulin G (IgG)Geometric Mean Concentrations (GMCs) at 30 days postvaccination (Day 30) with V114 or Prevnar 13™ by each vaccination group.

Primary Endpoint/Outcome

Following vaccination with V114:

• Solicited injection-site AEs from Day 1 through Day 14 postvaccination

• Solicited systemic AEs from Day 1 through Day 14 postvaccination

• Vaccine-related serious adverse events (SAEs) through completion of study participation

• Anti-PnPs serotype-specific IgG responses for the 15 serotypes contained in V114 at Day 30

Study Population

HIV infected children 6 to 17 years of age inclusive

Investigators

Dr Faeezah Patel, Principal Investigator

Dr Masebole Masenya

Dr Elizea Horne

Prof Lee Fairlie

Sponsors/Donors

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. (hereafter referred to as the Sponsor or MSD)

Latest Update: 23 August 2021

For more about SAPRIN please email rhicomms@wrhi.ac.za