COVID-19 Vaccine (ChAdOx1 nCoV-19) Trial in South African Adults With and Without HIV-infection

NCT04444674 | Unknown Phase 1 DMC

• 1 other identifier: ChAdOx1 nCoV-19_ZA_phI/II v4.1
• Study Type: interventional
• Target: 2,130
• Locations: 1 country
• Sites: 7

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.

Conditions

Coronavirus

Outcome Measures

Primary Outcomes (5)

• 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

  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.

  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

  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

  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

  Up to 12 months post enrollment

Secondary Outcomes (2)

• Assess humoral Immunogenicity of ChAdOx1 nCoV-19 in HIV-negative adults (immunogenicity)

  Up to 12 months post enrollment

• Assess cellular Immunogenicity of ChAdOx1 nCoV-19 in HIV-negative adults (immunogenicity)

  Up to 12 months post enrollment

Other Outcomes (2)

• Assess Fc effector functionality in participants who receive ChAdOx1 nCoV-19 vaccine or placebo

  Up to 12 months post enrollment

• Assess B cell responses to SARS-CoV-2 spike trimer and/or the receptor binding domain in participants who receive ChAdOx1 nCoV-19 vaccine or placebo

  Up to 12 months post enrollment

Study Arms (8)

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.

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.

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.

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.

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.

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.

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.

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.

Biological: Normal saline 0.9%

Interventions

ChAdOx1 nCoV-19 BIOLOGICAL

Dose of 5-7.5x10\^10vp of ChAdOx1 nCoV-19

Group 1- IP; Group 2a- IP; Group 2b- IP; Group 3- IP

Normal saline 0.9% BIOLOGICAL

Normal saline 0.9% as placebo

Group 1- placebo; Group 2a- placebo; Group 2b- placebo; Group 3- placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Oxford: lead
• Medical Research Council, South Africa: collaborator
• Bill and Melinda Gates Foundation: collaborator
• Wits Health Consortium (Pty) Ltd: collaborator
• University of Witwatersrand, South Africa: collaborator

Study Sites (7)

PHRU Kliptown

Johannesburg, Gauteng, 1811, South Africa

Location

Soweto Clinical Trials Centre

Johannesburg, Gauteng, 1818, South Africa

Location

Wits RHI Shandukani Research Centre

Johannesburg, Gauteng, 2001, South Africa

Location

Setshaba Research Centre (SRC)

Soshanguve, Gauteng, 0152, South Africa

Location

Chris Hani Baragwanath Academic Hospital - DST/NRF VPD RMPRU

Soweto, Gauteng, 2013, South Africa

Location

FAMCRU

Cape Town, Western Cape, 7505, South Africa

Location

Groote Schuur hospital, Lung infection and immunity unit, UCT

Cape Town, Western Cape, 7925, South Africa

Location

Related Publications (7)

• 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.

  PMID: 37149443 DERIVED

• Smith 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.

  PMID: 36851662 DERIVED

• Madhi 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.

  PMID: 36273491 DERIVED

• Madhi 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.

  PMID: 34416193 DERIVED

• Madhi 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.

  PMID: 33725432 DERIVED

• Voysey 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.

  PMID: 33617777 DERIVED

• Voysey 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.

  PMID: 33306989 DERIVED

MeSH Terms

Conditions

Coronavirus Infections

Interventions

ChAdOx1 nCoV-19; Saline Solution

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Vaccines, DNA; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Vaccines; Biological Products; Complex Mixtures; COVID-19 Vaccines; Viral Vaccines; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Shabir A Madhi, MD, PhD

  University of Witwatersrand, South Africa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded, placebo controlled. Pharmacist and vaccine administrators will be unblinded only. DSMB will be unblinded if required to assess safety signal
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: June 15, 2020
• First Posted: June 23, 2020
• Study Start: June 24, 2020
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2021
• Last Updated: November 27, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: within 1 year of trial completion
• Access Criteria: 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.

Locations

ZA (7)