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.
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.
Biological: ChAdOx1 nCoV-19
Dose of 5-7.5x10^10vp of ChAdOx1 nCoV-19
Biological: Normal saline 0.9%
Normal saline 0.9% as placebo
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-19.
- 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-19.
- 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.
- History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in
situ).
- History of serious psychiatric condition likely to affect participation in the study.
- Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or
prior history of significant bleeding or bruising following IM injections or
venipuncture.
- Any other serious chronic illness requiring hospital specialist supervision.
- Chronic respiratory diseases, including asthma
- Chronic cardiovascular disease, gastrointestinal disease, liver disease, renal
disease, endocrine disorder and neurological illness
- Seriously overweight (BMI ≥ 40 Kg/m2)
- Suspected or known current alcohol abuse as defined by an alcohol intake of greater
than 42 units every week.
- Suspected or known injecting drug abuse in the 5 years preceding enrollment.
- Any clinically significant abnormal finding on screening urinalysis.
- Any other significant disease, disorder or finding which may significantly increase
the risk to the participant because of participation in the study, affect the ability
of the participant to participate in the study or impair interpretation of the study
data.
- History of laboratory confirmed COVID-19 illness or known contact with a person that
was infected with SARS-COV-2.
- New onset of fever or a cough or shortness of breath in the 30 days preceding
screening and/or enrollment
- Travel history to any other country with widespread epidemic since January 2020
- In addition to above, Group 1 & 2 participants need to fulfill the following exclusion
criteria: Any confirmed or suspected immunosuppressive or immunodeficient state,
including HIV infection; asplenia; recurrent severe infections and chronic use (more
than 14 days) immunosuppressant medication within the past 6 months ( topical steroids
are allowed).
- Any confirmed or suspected immunosuppressive or immunodeficient state (except HIV
infection for Group-3), asplenia, recurrent severe infections and chronic use (more
than 14 days) immunosuppressant medication within the past 6 months (topical steroids
are allowed).
PHRU Kliptown
Johannesburg, Gauteng, South Africa
Soweto Clinical Trials Centre
Johannesburg, Gauteng, South Africa
Wits RHI Shandukani Research Centre
Johannesburg, Gauteng, South Africa
Setshaba Research Centre (SRC)
Soshanguve, Gauteng, South Africa
Chris Hani Baragwanath Academic Hospital - DST/NRF VPD RMPRU
Soweto, Gauteng, South Africa
FAMCRU
Cape Town, Western Cape, South Africa
Groote Schuur hospital, Lung infection and immunity unit, UCT
Cape Town, Western Cape, South Africa
Shabir A Madhi, MD, PhD, Principal Investigator
University of Witwatersrand, South Africa