NVX2019nCOV501

A Phase 2a/b, Randomized, Observer-Blinded, Placebo-Controlled Study to Evaluate the Efficacy, Immunogenicity, and Safety of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 rS) with Matrix-M™ Adjuvant in South African Adults Living Without HIV, and Safety and Immunogenicity in Adults Living With HIV.

Rationale

Conducted during the peak of the COVID-19 pandemic in South Africa, this study aims to inform vaccine development in both HIV-negative and HIV-positive populations. The results will support decisions for emergency use authorisation and/or Phase 3 trials, particularly in regions with high COVID-19 transmission.

This pivotal study assesses the SARS-CoV-2 rS vaccine with Matrix-M™ adjuvant (developed by Novavax) in a South African population. It aims to generate critical evidence on efficacy, immune response, and safety in both HIV-negative and medically stable HIV-positive adults.

Launched at the height of anticipated COVID-19 transmission in South Africa in July 2020, this study contributes to global efforts to accelerate emergency use authorization and Phase 3 evaluation of COVID-19 vaccines in diverse populations.

Primary Objectives

Cohort 1: HIV-Negative Adults

• Evaluate efficacy against mild, moderate, or severe PCR-confirmed COVID-19 in serologically naïve adults.

• Assess safety through reactogenicity and adverse event (AE) profiles.

• Measure immune response (IgG and ACE2 inhibition) post-vaccination.

Cohort 2: HIV-Positive Adults

• Assess safety and immunogenicity in medically stable HIV-positive adults.

• Evaluate antibody responses post-vaccination, stratified by baseline serostatus.

Secondary Objectives

• Examine immune durability and kinetics.

• Assess vaccine efficacy against hospitalisation.

• Describe symptom severity and illness duration.

• Investigate neutralising antibody responses and binding inhibition patterns.

Study Design

• Type: Phase 2a/b, randomized, observer-blinded, placebo-controlled

• Population:

  • Cohort 1: 2,960–4,164 HIV-negative adults aged 18–84

  • Cohort 2: ~240 HIV-positive adults aged 18–64

• Sample Size: 3,200–4,404 participants across both cohorts

• Sites: Up to 15 research sites in South Africa

• Randomization: 1:1 ratio (vaccine vs. placebo)

The trial is staged for safety monitoring, with early enrollees assessed before full rollout. Screening includes SARS-CoV-2 PCR and HIV testing. The study excludes those with active SARS-CoV-2 infection or moderate/severe immunosuppression (for HIV-positive cohort).

Investigators

• Prof Lee Fairlie, Principal Investigator
• Dr Gabrielle Benade, co-Principal Investigator
• Dr Faeezah Patel, Sub Investigator
• Dr Masebole Masenya, Sub Investigator
• Dr Elizea Horne, Sub-Investigator
• Dr Alden Nicholas Geldenhuys, Sub Investigator
• Dr Mrinmayee Dhar, Sub Investigator

Sponsors/Donors

• Novavax Inc

Latest Update:

23 August 2021

For more about NVX2019nCOV501 please email rhicomms@wrhi.ac.za