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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Coronavirus
- Sponsor
- University of Oxford
- Enrollment
- 2130
- Locations
- 7
- Primary Endpoint
- Assess humoral immunogenicity of ChAdOx1 nCoV-19 in people living with HIV
- Last Updated
- 5 years ago
Overview
Brief Summary
A Phase I/II, double-blinded, placebo-controlled, individually randomized trial to assess safety, immunogenicity and efficacy of the candidate Coronavirus disease (COVID-19) vaccine ChAdOx1 nCoV-19 in adults aged 18-65 years living with and without HIV in South Africa. The vaccine or placebo will be administered via an intramuscular injection into the deltoid muscle of the non-dominant arm.
Detailed Description
A total of 2070 participants will be enrolled into the trial; 1970 HIV-uninfected and 100 people living with HIV. There will be 4 trial groups, group 1 (n=50; intensive safety \& immunogenicity cohort, HIV negative), group 2a (n=250; safety, intense immunogenicity \& efficacy), group 2b (n=1650; safety, immunogenicity \& vaccine efficacy) and group 3 (n=100, intensive safety \& immunogenicity cohort, HIV positive). Participants will be followed up for 12 months after enrollment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy adults aged 18-65 years.
- •Documented result of not being infected with HIV (including screening by a rapid HIV antibody test) within two weeks of randomization into the study for Group-1 and Group-2 participants only.
- •Able and willing (in the Investigator's opinion) to comply with all study requirements.
- •Willing to allow investigators review available medical records, and review all medical and laboratory records if participant is admitted to hospital with respiratory tract infection suspected or confirmed to be COVID-
- •For females only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening (within 14 days of randomization) or vaccination.
- •For Group-3 only (i.e. HIV-infected), need to have been on anti-retroviral treatment for at least three months and HIV-1 viral load is \<1,000 copies/ml within two weeks of randomization.
- •Agreement to refrain from blood donation during the course of the study.
- •Provide written informed consent.
Exclusion Criteria
- •Planned receipt of any vaccine other (licensed or investigational) than the study intervention within 30 days before and after each study vaccination.
- •Use of any unproven registered and unregistered treatments for COVID-
- •Prior receipt of an investigational or licensed vaccine likely to impact on interpretation of the trial data (e.g. Adenovirus vectored vaccines, any coronavirus vaccines).
- •Administration of immunoglobulins and/ or any blood products within the three months preceding the planned administration of the vaccine candidate.
- •HBSAg positivity on the screening sample.
- •Grade 2 or higher level of abnormality for FBC, U\&E or LFT based on DAIDS Grading Criteria (Version 2.1, July 2017)
- •History of allergic disease or reactions likely to be exacerbated by any component of the ChAdOx1 nCoV-19 vaccine.
- •Any history of hereditary angioedema or idiopathic angioedema.
- •Any history of anaphylaxis in relation to vaccination.
- •Pregnancy, lactation or willingness/intention to become pregnant during the study.
Outcomes
Primary Outcomes
Assess humoral immunogenicity of ChAdOx1 nCoV-19 in people living with HIV
Time Frame: Up to 12 months post enrollment
Assessing Enzyme-linked immunosorbent assay (ELISA) or fluorescence based micro-bead immunosorbent assay on luminex platform to quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates) and Virus neutralising antibody (NAb) assays against live and/or pseudotyped SARS-CoV-2 virus
Determine if there is a reduction of severe and non-severe COVID-19 disease in HIV-negative adults who receive candidate vaccine ChAdOx1 nCoV-19 compared to placebo recipients (efficacy)
Time Frame: Up to 12 months post enrollment
Virologically-confirmed COVID-19 clinical disease will be defined as an acute respiratory illness that is clinically consistent with COVID-19 disease, AND SARS-CoV-2 RT-PCR positivity.
Assess cellular Immunogenicity of ChAdOx1 nCoV-19 in people living with HIV (immunogenicity)
Time Frame: Up to 12 months post enrollment
Assessing the Interferon-gamma (IFN-γ) enzyme- linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein and Th1 and Th2 cytokine response profile at 3-4 days after vaccination
Assess the incidence of adverse events (intervention-related and intervention-unrelated) in HIV-negative adults aged 18-65 year receiving candidate ChAdOx1 nCoV-19 vaccine or placebo (safety)
Time Frame: Up to 12 months post enrollment
Number of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination, and unsolicited adverse events for 28 days following vaccination. Assess occurrence of disease enhancement episodes and serious adverse events in year post vaccination
Assess the incidence of adverse events (intervention-related and intervention-unrelated) in HIV-positive adults aged 18-65 year receiving candidate ChAdOx1 nCoV-19 vaccine or placebo (safety)
Time Frame: Up to 12 months post enrollment
Number of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination, and unsolicited adverse events for 28 days following vaccination. Assess occurrence of disease enhancement episodes and serious adverse events in year post vaccination
Secondary Outcomes
- Assess cellular Immunogenicity of ChAdOx1 nCoV-19 in HIV-negative adults (immunogenicity)(Up to 12 months post enrollment)
- Assess humoral Immunogenicity of ChAdOx1 nCoV-19 in HIV-negative adults (immunogenicity)(Up to 12 months post enrollment)