CoronavirusPhase 1/2NCT04444674
COVID-19 Vaccine (ChAdOx1 nCoV-19) Trial in South African Adults With and Without HIV-infection
A Phase 1/2 study testing ChAdOx1 nCoV-19 and Normal saline 0.9% in people with Coronavirus, run by University of Oxford at 7 sites in South Africa.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Coronavirus
- What is being tested?
- ChAdOx1 nCoV-19 and Normal saline 0.9%
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,130 participants
- Where
- 7 sitesSouth Africa
- Study dates
- 24 Jun 2020to Dec 2021
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
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- 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).
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
South Africa7 sites
FAMCRU
Cape Town, Western Cape, 7505
Groote Schuur hospital, Lung infection and immunity unit, UCT
Cape Town, Western Cape, 7925
PHRU Kliptown
Johannesburg, Gauteng, 1811
Soweto Clinical Trials Centre
Johannesburg, Gauteng, 1818
Wits RHI Shandukani Research Centre
Johannesburg, Gauteng, 2001
Setshaba Research Centre (SRC)
Soshanguve, Gauteng, 0152
Chris Hani Baragwanath Academic Hospital - DST/NRF VPD RMPRU
Soweto, Gauteng, 2013
About this study
Official title: 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
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.
Read the 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.
- Conditions
- Coronavirus
- Being tested
- ChAdOx1 nCoV-19, Normal saline 0.9%
- Medical subject headings
- Coronavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChAdOx1 nCoV-19Biological
Dose of 5-7.5x10^10vp of ChAdOx1 nCoV-19
Normal saline 0.9%Biological
Normal saline 0.9% as placebo
| Study group | Role | What they receive |
|---|---|---|
| Group 1- IP | Experimental | Participants (HIV-negative) will receive two doses of 5-7.5x10^10 vp ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 11 routine visits over a 12 month period. Receives: Biological: ChAdOx1 nCoV-19 |
| Group 1- placebo | Placebo comparator | Participants (HIV-negative) will receive two doses of Normal saline (0.9%) in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 11 routine visits over a 12 month period. Receives: Biological: Normal saline 0.9% |
| Group 2a- IP | Experimental | Participants (HIV-negative) will receive two doses of 5-7.5x10^10 vp ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 7 (1-dose) or 9 (2 doses) routine visits over a 12 month period. Receives: Biological: ChAdOx1 nCoV-19 |
| Group 2a- placebo | Placebo comparator | Participants (HIV-negative) will receive two doses of placebo in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 7 (1-dose) or 9 (2 doses) routine visits over a 12 month period. Receives: Biological: Normal saline 0.9% |
| Group 2b- IP | Experimental | Participants will receive two doses of 5-7.5x10^10 vp ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 5 (1-dose) or 6 (2 doses) routine visits over a 12 month period. Receives: Biological: ChAdOx1 nCoV-19 |
| Group 2b- placebo | Placebo comparator | Participants will receive two doses of placebo in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 5 (1-dose) or 6 (2 doses) routine visits over a 12 month period. Receives: Biological: Normal saline 0.9% |
| Group 3- IP | Experimental | Participants (HIV-positive) will receive two doses of 5-7.5x10^10 vp ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 11 routine visits over a 12 month period. Receives: Biological: ChAdOx1 nCoV-19 |
| Group 3- placebo | Placebo comparator | Participants (HIV-positive) will receive two doses of placebo in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 11 routine visits over a 12 month period. Receives: Biological: Normal saline 0.9% |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
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
Measured: Up to 12 months post enrollment
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)
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.
Measured: Up to 12 months post enrollment
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)
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
Measured: Up to 12 months post enrollment
Assess cellular Immunogenicity of ChAdOx1 nCoV-19 in people living with HIV (immunogenicity)
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
Measured: Up to 12 months post enrollment
Assess humoral immunogenicity of ChAdOx1 nCoV-19 in people living with HIV
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
Measured: Up to 12 months post enrollment
Secondary outcomes (2)
Assess humoral Immunogenicity of ChAdOx1 nCoV-19 in HIV-negative adults (immunogenicity)
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
Measured: Up to 12 months post enrollment
Assess cellular Immunogenicity of ChAdOx1 nCoV-19 in HIV-negative adults (immunogenicity)
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
Measured: Up to 12 months post enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2020
- Study start24 Jun 2020
- Primary completionDec 2020 (estimated)
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for CoronavirusStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Four groups will be enrolled to receive either one or two doses of investigational vaccine or placebo. Follow up intensity and blood draws differ between groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2,130 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Council, South Africa, Bill and Melinda Gates Foundation, Wits Health Consortium (Pty) Ltd, University of Witwatersrand, South Africa
- Responsible party
- Sponsor
- Investigators
- Shabir A Madhi, MD, PhD, Principal investigator, University of Witwatersrand, South Africa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04444674
- Sponsor's protocol ID
- ChAdOx1 nCoV-19_ZA_phI/II v4.1
- Status last verified
- Nov 2020
- First submitted
- 15 Jun 2020
- Last updated
- 27 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data accumulated from this study will be stored at RMPRU/ Wits. In collaboration with UK collaborators, we aim to make the data available, within one year of completion of the study to any investigators who wish to use the data to address any specific questions not directly addressed under the study objectives and which the data would lend itself to. De-identified data will be shared. Related trial documents will be available (protocol, ICFs, statistical analysis plan)
Publications
Koen AL, Izu A, Baillie V, Kwatra G, Cutland CL, Fairlie L, Padayachee SD, Dheda K, Barnabas SL, Bhorat QE, Briner C, Ahmed K, Bhikha S, Bhiman JN, du Plessis J, Esmail A, Horne E, Hwa SH, Oommen-Jose A, Lambe T, Laubscher M, Malahleha M, Benade G, McKenzie S, Oelofse S, Patel F, Pillay S, Rhead S, Rodel H, Taoushanis C, Tegally H, Thombrayil A, Villafana TL, Gilbert S, Pollard AJ, Madhi SA. Efficacy of primary series AZD1222 (ChAdOx1 nCoV-19) vaccination against SARS-CoV-2 variants of concern: Final analysis of a randomized, placebo-controlled, phase 1b/2 study in South African adults (COV005). Vaccine. 2023 May 26;41(23):3486-3492. doi: 10.1016/j.vaccine.2023.04.058. Epub 2023 Apr 27.
PubMed 37149443Smith M, Kwatra G, Izu A, Nel A, Cutland C, Ahmed K, Baillie V, Barnabas S, Bhorat Q, Briner C, Lazarus E, Dheda K, Fairlie L, Koen A, Madhi S, Blackburn JM. Longitudinal IgA and IgG Response, and ACE2 Binding Blockade, to Full-Length SARS-CoV-2 Spike Protein Variants in a Population of Black PLWH Vaccinated with ChAdOx1 nCoV-19. Viruses. 2023 Feb 6;15(2):448. doi: 10.3390/v15020448.
PubMed 36851662Madhi SA, Kwatra G, Richardson SI, Koen AL, Baillie V, Cutland CL, Fairlie L, Padayachee SD, Dheda K, Barnabas SL, Bhorat QE, Briner C, Ahmed K, Aley PK, Bhikha S, Bhorat AE, Esmail A, Horne E, Kaldine H, Mukendi CK, Madzorera VS, Manamela NP, Masilela M, Hermanus ST, Motlou T, Mzindle N, Oelofse S, Patel F, Rhead S, Rossouw L, Taoushanis C, van Eck S, Lambe T, Gilbert SC, Pollard AJ, Moore PL, Izu A. Durability of ChAdOx1 nCoV-19 (AZD1222) vaccine and hybrid humoral immunity against variants including omicron BA.1 and BA.4 6 months after vaccination (COV005): a post-hoc analysis of a randomised, phase 1b-2a trial. Lancet Infect Dis. 2023 Mar;23(3):295-306. doi: 10.1016/S1473-3099(22)00596-5. Epub 2022 Oct 20.
PubMed 36273491Madhi SA, Koen AL, Izu A, Fairlie L, Cutland CL, Baillie V, Padayachee SD, Dheda K, Barnabas SL, Bhorat QE, Briner C, Aley PK, Bhikha S, Hermanus T, Horne E, Jose A, Kgagudi P, Lambe T, Masenya M, Masilela M, Mkhize N, Moultrie A, Mukendi CK, Moyo-Gwete T, Nana AJ, Nzimande A, Patel F, Rhead S, Taoushanis C, Thombrayil A, van Eck S, Voysey M, Villafana TL, Vekemans J, Gilbert SC, Pollard AJ, Moore PL, Kwatra G; Wits VIDA COVID team. Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in people living with and without HIV in South Africa: an interim analysis of a randomised, double-blind, placebo-controlled, phase 1B/2A trial. Lancet HIV. 2021 Sep;8(9):e568-e580. doi: 10.1016/S2352-3018(21)00157-0. Epub 2021 Aug 17.
PubMed 34416193Madhi SA, Baillie V, Cutland CL, Voysey M, Koen AL, Fairlie L, Padayachee SD, Dheda K, Barnabas SL, Bhorat QE, Briner C, Kwatra G, Ahmed K, Aley P, Bhikha S, Bhiman JN, Bhorat AE, du Plessis J, Esmail A, Groenewald M, Horne E, Hwa SH, Jose A, Lambe T, Laubscher M, Malahleha M, Masenya M, Masilela M, McKenzie S, Molapo K, Moultrie A, Oelofse S, Patel F, Pillay S, Rhead S, Rodel H, Rossouw L, Taoushanis C, Tegally H, Thombrayil A, van Eck S, Wibmer CK, Durham NM, Kelly EJ, Villafana TL, Gilbert S, Pollard AJ, de Oliveira T, Moore PL, Sigal A, Izu A; NGS-SA Group; Wits-VIDA COVID Group. Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant. N Engl J Med. 2021 May 20;384(20):1885-1898. doi: 10.1056/NEJMoa2102214. Epub 2021 Mar 16.
PubMed 33725432Voysey M, Costa Clemens SA, Madhi SA, Weckx LY, Folegatti PM, Aley PK, Angus B, Baillie VL, Barnabas SL, Bhorat QE, Bibi S, Briner C, Cicconi P, Clutterbuck EA, Collins AM, Cutland CL, Darton TC, Dheda K, Dold C, Duncan CJA, Emary KRW, Ewer KJ, Flaxman A, Fairlie L, Faust SN, Feng S, Ferreira DM, Finn A, Galiza E, Goodman AL, Green CM, Green CA, Greenland M, Hill C, Hill HC, Hirsch I, Izu A, Jenkin D, Joe CCD, Kerridge S, Koen A, Kwatra G, Lazarus R, Libri V, Lillie PJ, Marchevsky NG, Marshall RP, Mendes AVA, Milan EP, Minassian AM, McGregor A, Mujadidi YF, Nana A, Padayachee SD, Phillips DJ, Pittella A, Plested E, Pollock KM, Ramasamy MN, Ritchie AJ, Robinson H, Schwarzbold AV, Smith A, Song R, Snape MD, Sprinz E, Sutherland RK, Thomson EC, Torok ME, Toshner M, Turner DPJ, Vekemans J, Villafana TL, White T, Williams CJ, Douglas AD, Hill AVS, Lambe T, Gilbert SC, Pollard AJ; Oxford COVID Vaccine Trial Group. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials. Lancet. 2021 Mar 6;397(10277):881-891. doi: 10.1016/S0140-6736(21)00432-3. Epub 2021 Feb 19.
PubMed 33617777Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, Angus B, Baillie VL, Barnabas SL, Bhorat QE, Bibi S, Briner C, Cicconi P, Collins AM, Colin-Jones R, Cutland CL, Darton TC, Dheda K, Duncan CJA, Emary KRW, Ewer KJ, Fairlie L, Faust SN, Feng S, Ferreira DM, Finn A, Goodman AL, Green CM, Green CA, Heath PT, Hill C, Hill H, Hirsch I, Hodgson SHC, Izu A, Jackson S, Jenkin D, Joe CCD, Kerridge S, Koen A, Kwatra G, Lazarus R, Lawrie AM, Lelliott A, Libri V, Lillie PJ, Mallory R, Mendes AVA, Milan EP, Minassian AM, McGregor A, Morrison H, Mujadidi YF, Nana A, O'Reilly PJ, Padayachee SD, Pittella A, Plested E, Pollock KM, Ramasamy MN, Rhead S, Schwarzbold AV, Singh N, Smith A, Song R, Snape MD, Sprinz E, Sutherland RK, Tarrant R, Thomson EC, Torok ME, Toshner M, Turner DPJ, Vekemans J, Villafana TL, Watson MEE, Williams CJ, Douglas AD, Hill AVS, Lambe T, Gilbert SC, Pollard AJ; Oxford COVID Vaccine Trial Group. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021 Jan 9;397(10269):99-111. doi: 10.1016/S0140-6736(20)32661-1. Epub 2020 Dec 8.
PubMed 33306989
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04444674
- Acronym / sponsor ID
- ChAdOx1 nCoV-19_ZA_phI/II v4.1
- Conditions
- Coronavirus
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 2,130 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Medical Research Council, South Africa, Bill and Melinda Gates Foundation, Wits Health Consortium (Pty) Ltd, University of Witwatersrand, South Africa
- Study start
- 24 Jun 2020 (actual)
- Primary completion
- Dec 2020 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 23 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 8
- Model description
- Four groups will be enrolled to receive either one or two doses of investigational vaccine or placebo. Follow up intensity and blood draws differ between groups
| Arm | Type | Receives |
|---|---|---|
| Group 1- IP | Experimental | Biological: ChAdOx1 nCoV-19Participants (HIV-negative) will receive two doses of 5-7.5x10^10 vp ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 11 routine visits over a 12 month period. |
| Group 1- placebo | Placebo comparator | Biological: Normal saline 0.9%Participants (HIV-negative) will receive two doses of Normal saline (0.9%) in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 11 routine visits over a 12 month period. |
| Group 2a- IP | Experimental | Biological: ChAdOx1 nCoV-19Participants (HIV-negative) will receive two doses of 5-7.5x10^10 vp ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 7 (1-dose) or 9 (2 doses) routine visits over a 12 month period. |
| Group 2a- placebo | Placebo comparator | Biological: Normal saline 0.9%Participants (HIV-negative) will receive two doses of placebo in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 7 (1-dose) or 9 (2 doses) routine visits over a 12 month period. |
| Group 2b- IP | Experimental | Biological: ChAdOx1 nCoV-19Participants will receive two doses of 5-7.5x10^10 vp ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 5 (1-dose) or 6 (2 doses) routine visits over a 12 month period. |
| Group 2b- placebo | Placebo comparator | Biological: Normal saline 0.9%Participants will receive two doses of placebo in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 5 (1-dose) or 6 (2 doses) routine visits over a 12 month period. |
| Group 3- IP | Experimental | Biological: ChAdOx1 nCoV-19Participants (HIV-positive) will receive two doses of 5-7.5x10^10 vp ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 11 routine visits over a 12 month period. |
| Group 3- placebo | Placebo comparator | Biological: Normal saline 0.9%Participants (HIV-positive) will receive two doses of placebo in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 11 routine visits over a 12 month period. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (26 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ChAdOx1 nCoV-19Dose of 5-7.5x10^10vp of ChAdOx1 nCoV-19 | Biological | Group 1- IP, Group 2a- IP, Group 2b- IP, Group 3- IP |
| Normal saline 0.9%Normal saline 0.9% as placebo | Biological | Group 1- placebo, Group 2a- placebo, Group 2b- placebo, Group 3- placebo |
Primary outcome
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
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 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
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 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
2 secondary outcomes
Assess humoral Immunogenicity of ChAdOx1 nCoV-19 in HIV-negative adults (immunogenicity)
Time frame: Up to 12 months post enrollment
Assess cellular Immunogenicity of ChAdOx1 nCoV-19 in HIV-negative adults (immunogenicity)
Time frame: Up to 12 months post enrollment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2020.
- Derived from this study: PubMed 37149443Koen AL, Izu A, Baillie V, Kwatra G, Cutland CL, Fairlie L, Padayachee SD, Dheda K, Barnabas SL, Bhorat QE, Briner C, Ahmed K, Bhikha S, Bhiman JN, du Plessis J, Esmail A, Horne E, Hwa SH, Oommen-Jose A, Lambe T, Laubscher M, Malahleha M, Benade G, McKenzie S, Oelofse S, Patel F, Pillay S, Rhead S, Rodel H, Taoushanis C, Tegally H, Thombrayil A, Villafana TL, Gilbert S, Pollard AJ, Madhi SA. Efficacy of primary series AZD1222 (ChAdOx1 nCoV-19) vaccination against SARS-CoV-2 variants of concern: Final analysis of a randomized, placebo-controlled, phase 1b/2 study in South African adults (COV005). Vaccine. 2023 May 26;41(23):3486-3492. doi: 10.1016/j.vaccine.2023.04.058. Epub 2023 Apr 27.
- Derived from this study: PubMed 36851662Smith M, Kwatra G, Izu A, Nel A, Cutland C, Ahmed K, Baillie V, Barnabas S, Bhorat Q, Briner C, Lazarus E, Dheda K, Fairlie L, Koen A, Madhi S, Blackburn JM. Longitudinal IgA and IgG Response, and ACE2 Binding Blockade, to Full-Length SARS-CoV-2 Spike Protein Variants in a Population of Black PLWH Vaccinated with ChAdOx1 nCoV-19. Viruses. 2023 Feb 6;15(2):448. doi: 10.3390/v15020448.
- Derived from this study: PubMed 36273491Madhi SA, Kwatra G, Richardson SI, Koen AL, Baillie V, Cutland CL, Fairlie L, Padayachee SD, Dheda K, Barnabas SL, Bhorat QE, Briner C, Ahmed K, Aley PK, Bhikha S, Bhorat AE, Esmail A, Horne E, Kaldine H, Mukendi CK, Madzorera VS, Manamela NP, Masilela M, Hermanus ST, Motlou T, Mzindle N, Oelofse S, Patel F, Rhead S, Rossouw L, Taoushanis C, van Eck S, Lambe T, Gilbert SC, Pollard AJ, Moore PL, Izu A. Durability of ChAdOx1 nCoV-19 (AZD1222) vaccine and hybrid humoral immunity against variants including omicron BA.1 and BA.4 6 months after vaccination (COV005): a post-hoc analysis of a randomised, phase 1b-2a trial. Lancet Infect Dis. 2023 Mar;23(3):295-306. doi: 10.1016/S1473-3099(22)00596-5. Epub 2022 Oct 20.
- Derived from this study: PubMed 34416193Madhi SA, Koen AL, Izu A, Fairlie L, Cutland CL, Baillie V, Padayachee SD, Dheda K, Barnabas SL, Bhorat QE, Briner C, Aley PK, Bhikha S, Hermanus T, Horne E, Jose A, Kgagudi P, Lambe T, Masenya M, Masilela M, Mkhize N, Moultrie A, Mukendi CK, Moyo-Gwete T, Nana AJ, Nzimande A, Patel F, Rhead S, Taoushanis C, Thombrayil A, van Eck S, Voysey M, Villafana TL, Vekemans J, Gilbert SC, Pollard AJ, Moore PL, Kwatra G; Wits VIDA COVID team. Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in people living with and without HIV in South Africa: an interim analysis of a randomised, double-blind, placebo-controlled, phase 1B/2A trial. Lancet HIV. 2021 Sep;8(9):e568-e580. doi: 10.1016/S2352-3018(21)00157-0. Epub 2021 Aug 17.
- Derived from this study: PubMed 33725432Madhi SA, Baillie V, Cutland CL, Voysey M, Koen AL, Fairlie L, Padayachee SD, Dheda K, Barnabas SL, Bhorat QE, Briner C, Kwatra G, Ahmed K, Aley P, Bhikha S, Bhiman JN, Bhorat AE, du Plessis J, Esmail A, Groenewald M, Horne E, Hwa SH, Jose A, Lambe T, Laubscher M, Malahleha M, Masenya M, Masilela M, McKenzie S, Molapo K, Moultrie A, Oelofse S, Patel F, Pillay S, Rhead S, Rodel H, Rossouw L, Taoushanis C, Tegally H, Thombrayil A, van Eck S, Wibmer CK, Durham NM, Kelly EJ, Villafana TL, Gilbert S, Pollard AJ, de Oliveira T, Moore PL, Sigal A, Izu A; NGS-SA Group; Wits-VIDA COVID Group. Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant. N Engl J Med. 2021 May 20;384(20):1885-1898. doi: 10.1056/NEJMoa2102214. Epub 2021 Mar 16.
- Derived from this study: PubMed 33617777Voysey M, Costa Clemens SA, Madhi SA, Weckx LY, Folegatti PM, Aley PK, Angus B, Baillie VL, Barnabas SL, Bhorat QE, Bibi S, Briner C, Cicconi P, Clutterbuck EA, Collins AM, Cutland CL, Darton TC, Dheda K, Dold C, Duncan CJA, Emary KRW, Ewer KJ, Flaxman A, Fairlie L, Faust SN, Feng S, Ferreira DM, Finn A, Galiza E, Goodman AL, Green CM, Green CA, Greenland M, Hill C, Hill HC, Hirsch I, Izu A, Jenkin D, Joe CCD, Kerridge S, Koen A, Kwatra G, Lazarus R, Libri V, Lillie PJ, Marchevsky NG, Marshall RP, Mendes AVA, Milan EP, Minassian AM, McGregor A, Mujadidi YF, Nana A, Padayachee SD, Phillips DJ, Pittella A, Plested E, Pollock KM, Ramasamy MN, Ritchie AJ, Robinson H, Schwarzbold AV, Smith A, Song R, Snape MD, Sprinz E, Sutherland RK, Thomson EC, Torok ME, Toshner M, Turner DPJ, Vekemans J, Villafana TL, White T, Williams CJ, Douglas AD, Hill AVS, Lambe T, Gilbert SC, Pollard AJ; Oxford COVID Vaccine Trial Group. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials. Lancet. 2021 Mar 6;397(10277):881-891. doi: 10.1016/S0140-6736(21)00432-3. Epub 2021 Feb 19.
- Derived from this study: PubMed 33306989Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, Angus B, Baillie VL, Barnabas SL, Bhorat QE, Bibi S, Briner C, Cicconi P, Collins AM, Colin-Jones R, Cutland CL, Darton TC, Dheda K, Duncan CJA, Emary KRW, Ewer KJ, Fairlie L, Faust SN, Feng S, Ferreira DM, Finn A, Goodman AL, Green CM, Green CA, Heath PT, Hill C, Hill H, Hirsch I, Hodgson SHC, Izu A, Jackson S, Jenkin D, Joe CCD, Kerridge S, Koen A, Kwatra G, Lazarus R, Lawrie AM, Lelliott A, Libri V, Lillie PJ, Mallory R, Mendes AVA, Milan EP, Minassian AM, McGregor A, Morrison H, Mujadidi YF, Nana A, O'Reilly PJ, Padayachee SD, Pittella A, Plested E, Pollock KM, Ramasamy MN, Rhead S, Schwarzbold AV, Singh N, Smith A, Song R, Snape MD, Sprinz E, Sutherland RK, Tarrant R, Thomson EC, Torok ME, Toshner M, Turner DPJ, Vekemans J, Villafana TL, Watson MEE, Williams CJ, Douglas AD, Hill AVS, Lambe T, Gilbert SC, Pollard AJ; Oxford COVID Vaccine Trial Group. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021 Jan 9;397(10269):99-111. doi: 10.1016/S0140-6736(20)32661-1. Epub 2020 Dec 8.
- Individual participant dataSharing planned: Yes. The data accumulated from this study will be stored at RMPRU/ Wits. In collaboration with UK collaborators, we aim to make the data available, within one year of completion of the study to any investigators who wish to use the data to address any specific questions not directly addressed under the study objectives and which the data would lend itself to. De-identified data will be shared. Related trial documents will be available (protocol, ICFs, statistical analysis plan)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shabir A Madhi, MD, PhD principal investigator
University of Witwatersrand, South Africa
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ChAdOx1 nCoV-19 and Normal saline 0.9% in people with Coronavirus, run by University of Oxford at 7 sites in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04444674, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2020.