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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04444674
Recruitment Status : Recruiting
First Posted : June 23, 2020
Last Update Posted : August 5, 2020
Sponsor:
Collaborators:
Medical Research Council, South Africa
Bill and Melinda Gates Foundation
Wits Health Consortium (Pty) Ltd
University of Oxford
Information provided by (Responsible Party):
Shabir Madhi, University of Witwatersrand, South Africa

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.

Condition or disease Intervention/treatment Phase
Coronavirus Biological: ChAdOx1 nCoV-19 Biological: Normal saline 0.9% Phase 1 Phase 2

Detailed Description:

A total of 2000 participants will be enrolled into the trial; 1950 HIV-uninfected and 50 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=50, intensive safety & immunogenicity cohort, HIV positive).

Participants will be followed up for 12 months after enrollment.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double-blinded, placebo controlled. Pharmacist and vaccine administrators will be unblinded only. DSMB will be unblinded if required to assess safety signal
Primary Purpose: Prevention
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
Actual Study Start Date : June 24, 2020
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group 1- IP
Participants (HIV-negative) will receive two doses of 5x10^10vp 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
Dose of 5x10^10vp of ChAdOx1 nCoV-19

Placebo Comparator: Group 1- placebo
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%
Normal saline 0.9% as placebo

Experimental: Group 2a- IP
Participants (HIV-negative) will receive ONE OR TWO doses of 5x10^10vp 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
Dose of 5x10^10vp of ChAdOx1 nCoV-19

Placebo Comparator: Group 2a- placebo
Participants (HIV-negative) will receive ONE OR 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%
Normal saline 0.9% as placebo

Experimental: Group 2b- IP
Participants will receive ONE OR TWO doses of 5x10^10vp 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
Dose of 5x10^10vp of ChAdOx1 nCoV-19

Placebo Comparator: Group 2b- placebo
Participants will receive ONE OR 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%
Normal saline 0.9% as placebo

Experimental: Group 3- IP
Participants (HIV-positive) will receive two doses of 5x10^10vp 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
Dose of 5x10^10vp of ChAdOx1 nCoV-19

Placebo Comparator: Group 3- placebo
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%
Normal saline 0.9% as placebo




Primary Outcome Measures :
  1. 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


  2. 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.

  3. 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


  4. 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

  5. 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


Secondary Outcome Measures :
  1. Assess humoral Immunogenicity of ChAdOx1 nCoV-19 in HIV-negative adults (immunogenicity) [ 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. Assess cellular Immunogenicity of ChAdOx1 nCoV-19 in HIV-negative adults (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


Other Outcome Measures:
  1. Assess Fc effector functionality in participants who receive ChAdOx1 nCoV-19 vaccine or placebo [ Time Frame: Up to 12 months post enrollment ]
    Cellular Fc effector functionality assays to measure the ability of vaccine elicited antibodies to mediate cellular cytotoxicity, complement deposition, and phagocytosis.

  2. 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 [ Time Frame: Up to 12 months post enrollment ]
    Flow cytometric sorting of plasmablasts and memory B cells to using spike and receptor binding domain "baits" to isolate SARS-CoV-2 specific B cells, sequence their immunoglobulin genes and define their epitope specificity.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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-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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04444674


Contacts
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Contact: Clare L Cutland, MBBCH, PhD +27-11-983-4283 cutlandc@rmpru.co.za

Locations
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South Africa
PHRU Kliptown Not yet recruiting
Johannesburg, Gauteng, South Africa, 1811
Contact: Erica Lazarus, MBCHB    +27-11-3424075    lazaruse@phru.co.za   
Soweto Clinical Trials Centre Recruiting
Johannesburg, Gauteng, South Africa, 1818
Contact: Qasim Bhorat, MD         
Wits RHI Shandukani Research Centre Recruiting
Johannesburg, Gauteng, South Africa, 2001
Contact: Lee Fairlie, MD    +27-11-358-55-2    lfairlie@wrhi.ac.za   
Contact: Thabile Msomi    +27-11-358-5475    tmsomi@wrhi.ac.za   
Setshaba Research Centre (SRC) Recruiting
Soshanguve, Gauteng, South Africa, 0152
Contact: Sherman Padayachee, MD    +27-12-7992422    spadayachee@setshaba.org.za   
Chris Hani Baragwanath Academic Hospital - DST/NRF VPD RMPRU Recruiting
Soweto, Gauteng, South Africa, 2013
Contact: Shabir A Madhi, MD PhD       madhis@rmpru.co.za   
Contact: Anthonet Koen, MBCHB       koena@rmpru.co.za   
FAMCRU Not yet recruiting
Cape Town, Western Cape, South Africa, 7505
Contact: Shaun Barnabas, MD, PhD    +27-21-9384153    barnabas@sun.ac.za   
Groote Schuur hospital, Lung infection and immunity unit, UCT Recruiting
Cape Town, Western Cape, South Africa, 7925
Contact: Keertan Dheda, MD, PhD    +27-21-404-7654    keertan.dheda@uct.ac.za   
Sponsors and Collaborators
University of Witwatersrand, South Africa
Medical Research Council, South Africa
Bill and Melinda Gates Foundation
Wits Health Consortium (Pty) Ltd
University of Oxford
Investigators
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Principal Investigator: Shabir A Madhi, MD, PhD University of Witwatersrand, South Africa
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Responsible Party: Shabir Madhi, Director, Respiratory and Meningeal Pathogens Research Unit, University of Witwatersrand, South Africa
ClinicalTrials.gov Identifier: NCT04444674    
Other Study ID Numbers: ChAdOx1 nCoV-19_ZA_phI/II
First Posted: June 23, 2020    Key Record Dates
Last Update Posted: August 5, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

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)

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases