Trial NCT04444674
Publication Koen A, medRxiv, 2022
Dates: 2020-06-24 to 2020-11-09
Funding: Mixed (UK Research and Innovation (For Vaccine supply only), The Bill and Melinda Gates Foundation and South African Medical Research Council)
Conflict of interest: Yes
| Methods | |
| RCT | |
| Location :
Multicenter / South Africa Follow-up duration (months): 16.2 | |
| • 0.33 to 0.5 ml ChAdOx1, 2 doses (n=1065) • Placebo, 2 doses (n=1065) |
|
| 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; 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) |
| Interventions | |
| Intervention
2 IM doses of 5 x 10^10vp ChAdOx1 nCoV-19, D0/28 |
|
| Control
2 IM doses of placebo, D0/28 | |
| Participants | |
| Randomized 2130 participants | |
| Characteristics of participants Type of participants: Healthy volunteers N=2130 1142 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: NR Age range: 18-65 | |
| Description of participants Healthy adults aged 18–65 years in 7 centres in South Africa | |
| Primary outcome | |
| In the register 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 ] 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 ] 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 ] 4.Assess cellular Immunogenicity of ChAdOx1 nCoV-19 in people living with HIV (immunogenicity) [ Time Frame: Up to 12 months post enrollment ] 5.Assess humoral immunogenicity of ChAdOx1 nCoV-19 in people living with HIV [ Time Frame: Up to 12 months post enrollment ] | |
| In the report VE in the context of polymerase chain reaction (PCR)-positive symptomatic COVID-19 occurring >14 days after the second dose of study drug, and safety | |
| Variants description | |
Variants
| |
| Description Variant name: Beta and Delta Direct evidence Methods: Prespecified analysis Missing outcome results: 1 case (2.3%) with no sequence data (control arm) | |
| Documents avalaible |
Protocol Yes. In English Statistical plan Yes Data-sharing stated:
Yes, One year after trial completion |
| Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review |
Variant beta: Some concerns |
| General comment |
This study was updated on March 25th, 2021 after the publication of an interim analyses of the COV005 trial.
The efficacy results against variant Beta were extracted and assessed. Results on all other outcomes, combined with trials COV001/002 (UK) and COV003 (Brazil) have been reported previously (Voysey, Lancet, 2021) and were already extracted and assessed.
This trial was updated on November 11th 2022, after publication of trial final results. Data for Confirmed Symptomatic COVID-19 Beta variant were obtained from Madhi S, N Engl J Med, 2021 and data for the Delta variant from Koen A, medRxiv, 2022. |