ChAdOx1 nCoV-19


An adaptive phase I/II randomized placebo-controlled trial to determine safety, immunogenicity and efficacy of non-replicating ChAdOx1 SARS-CoV-2 vaccine in South African adults living without HIV; and safety and immunogenicity in adults living with HIV.

Rationele

The COVID-19 pandemic has caused major disruption to healthcare systems with significant socioeconomic impacts. Containment measures have failed to stop the global spread of virus. There are currently no specific treatments available against COVID-19 and accelerated vaccine development is urgently needed. South Africa is still at an early stage of its COVID-19 outbreak, which is expected to start peaking toward the end of July 2020 but has already documented 3,500 cases and 58 deaths as of 22 April 2020 (Wordometer.info). Recent modelling data

indicates that globally there are likely to be 3-4 waves of COVID-19 outbreaks, possibly extending through to 2022. Live attenuated viruses have historically been among the most immunogenic platforms available, as they have the capacity to present multiple antigens across the viral life cycle in their native conformations. However, manufacturing live-attenuated viruses requires complex containment and biosafety measures. Furthermore, live-attenuated viruses carry the risks of inadequate attenuation causing disseminated disease, particularly in immunocompromised hosts. Given that severe disease and fatal COVID-19 disproportionally affect older adults with co-morbidities, making a live-attenuated virus vaccine is a less viable option. Replication

competent viral vectors could pose a similar threat for disseminated disease in the immuno-suppressed. Replication deficient vectors, however, avoid that risk while maintaining the advantages of native antigen presentation, elicitation of T cell immunity and the ability to express multiple antigens [15]. Subunit vaccines usually require the use of adjuvants and whilst DNA and RNA vaccines can offer manufacturing advantages, they are often poorly immunogenic requiring multiple doses, which is highly undesirable in the context of a pandemic.

Chimpanzee adenovirus vaccine vectors have been safely administered to thousands of people using a wide range of infectious disease targets. ChAdOx1 vectored vaccines have been given to over 320 participants with no safety concerns and have been shown to be highly immunogenic at single dose administration. Of relevance, a single dose of a ChAdOx1 vectored vaccine expressing full-length spike protein from another betacoronavirus (MERS-CoV) has shown to induce neutralising antibodies in recent clinical trials (Folegatti et.Al. 2020. Lancet Infect Dis, In press).

A phase I/II trial in healthy adults in the United Kingdom initiated recruitment in late April 2020. Data generated in the UK study will be used to support further larger phase II/III efficacy studies, which will include target groups at higher risk of severe disease. The trial to be conducted in South Africa will enrol adults living with and without HIV to assess safety, immunogenicity and efficacy of one and two doses of ChAdOx1-nCoV-19. The South African study on ChAdOx1-nCoV-19 (Group 1 enrolment) will only be initiated following review by the Data and Safety Monitoring Committee (which will oversee both the UK, South African and a planned study in Kenya) of the initial safety cohort (n=50) that will be enrolled in the UK. Enrolment into Group-1 of the study in South Africa will occur in tandem with opening of enrolment of the expanded immunogenicity and “efficacy-cohort” in the UK.

Primary and Co-Primary Objectives

In adults without HIV (HIV-uninfected)

  • To assess the safety of the candidate vaccine ChAdOx1 nCoV-19 in healthy HIV-uninfected adults.
  • To assess efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19, defined as virologically confirmed (PCR positive) COVID-19 disease cases that are sero-negative (naïve) for SARS-CoV-2 infection at time of randomization.

In adults living with HIV (HIV-infected)

  • To assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV in people living with HIV.
  • To evaluate the immunogenicity of ChAdOx1 nCoV-19 after first and second doses of vaccine.

Study Population

Healthy adult participants that are HIV-uninfected (Groups 1 and 2); and generally, well people living with HIV [Group 3]); aged 18-65 years across both groups will be enrolled.

Invetigators

  • Dr Lee Fairlie, Principal Investigator
  • Dr Faeezah Patel, Sub-investigator
  • Dr Maysseb Masenya, Sub-Investigator
  • Dr Elizea Horne, Sub-investigator
  • Dr Gabriella Benade, Sub-investigator
  • Dr Nadia Dawood, Sub-investigator
  • Alden Geldenhuys, Sub-investigator
  • Mrinmayee Dhar, Sub-Investigator
  • Tiffany Seef, Clinical associate

Donor

Wits Health Consortium (Pty) Ltd

Latest Update: 15 February 2021

For more about ChAdOx1 nCoV-19 please email rhicomms@wrhi.ac.za