Covid-19 Living Data

Trial NCT04516746
Publication Sobieszczyk M, J Clin Invest, 2022
Dates: 2020-08-28 to 2021-01-15
Funding: Mixed (AstraZeneca; the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority; the Infectious Diseases Clinical Research Consortium through the National Institute of Allergy and Infectious Diseases, part of the NIH)
Conflict of interest: Yes

Methods
	RCT
	Location : Multicenter / Chile, Peru, USA Follow-up duration (months): 6.27
	ChAdOx1 (n = 21,634) Placebo (n = 10,816)
Inclusion criteria	Adult, 18 years of age or older at the time of consent Increased risk of SARS-CoV-2 infection Medically stable such that, according to the judgment of the investigator, hospitalization within the trial period was not anticipated and the participant appeared likely to be able to remain in the trial through the end of protocol-specified follow-up Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies Women of childbearing potential were required to: Have a negative pregnancy test on the day of screening and on Day 1, and Use one highly effective form of birth control for at least 28 days prior to Day 1 and agree to continue using one highly effective form of birth control through 60 days following administration of the second dose of trial intervention Women were considered of childbearing potential unless they met either of the following criteria: surgically sterilized (including bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) or postmenopausal Capable of giving signed informed consent (or legally authorized representative able to provide consent)
Exclusion criteria	History of allergy to any component of the vaccine History of Guillain-Barré syndrome or any other demyelinating condition Significant infection or other acute illness, including fever over 100°F (over 37°C) on the day prior to or day of randomization History of laboratory-confirmed SARS-CoV-2 infection Any confirmed or suspected immunosuppressive or immunodeficient state, including asplenia Recurrent severe infections and use of immunosuppressant medication within the past 6 months (20 mg/kg/day or more of prednisone or its equivalent, given daily or on alternate days for 15 days or more within 30 days prior to administration of trial intervention) History of primary malignancy except for: Malignancy with low potential risk for recurrence after curative treatment (for example, history of childhood leukemia) or metastasis (for example, indolent prostate cancer) in the opinion of the site investigator, Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, Adequately treated uterine cervical carcinoma in situ without evidence of disease, Localized prostate cancer Clinically significant bleeding disorder (for example, factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following intramuscular injections or venipuncture Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, and neurological illness, as judged by the Investigator (mild/moderate well-controlled coexisting conditions are allowed) Any other significant disease, disorder, or finding that may have significantly increased the risk to the participant because of participation in the trial, affect the ability of the participant to participate in the trial, or impair interpretation of the trial data Receipt of, or planned receipt of investigational products indicated for the treatment or prevention of SARS-CoV-2 or Covid-19 For participants who became hospitalized with Covid-19, receipt of licensed treatment options and/or participation in investigational treatment studies was permitted Receipt of any vaccine (licensed or investigational) other than licensed influenza vaccines within 30 days prior to and after administration of trial intervention Receipt of immunoglobulins and/or any blood products within 3 months prior to administration of trial intervention or expected receipt during the period of trial follow-up Involvement in the planning and/or conduct of this trial (applied to both Sponsor staff and/or staff at the trial site) For women only: pregnancy (confirmed with positive pregnancy test) or breastfeeding Had donated 450 mL or more of blood products within 30 days prior to randomization or expected to donate within 90 days of administration of second dose of trial intervention
Interventions
	Intervention 2 IM doses of ChAdOx1 5×10^10 vp, 28 days apart
	Control 2 IM doses of saline placebo, 28 days apart
Participants
	Randomized 32,450 participants
	Characteristics of participants Type of participants: Adults N=32,450 18015 males Children: 0 Pregnant women: 0 Immunocompromized patients: 9 Mean age: Age range: 18-100
	Description of participants Adults (22% over 65 years) at high risk for exposure to SARS-CoV-2 and populations at increased risk for Covid-19 complications at 88 sites in USA, Chile, and Peru
Primary outcome
	In the register 1) Number of Participants Achieving Binary Response [ Time Frame: From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks ]; 2) Number of Participants With Adverse Events (AEs) Occurring Post Each Dose of Study Intervention [ Time Frame: From Day 1 up to 28 days post second dose of study intervention, approximately 57 days ]; 3) Number of Participants With Serious Adverse Events (SAE), Medically Attended Adverse Events (MAAE), and Adverse Event of Special Interest (AESI) Occurring Throughout the Study [ Time Frame: From Day 1 up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of approximately 27 weeks ]; 4) Number of Participants With Local and Systemic Solicited AEs in the Substudy Only [ Time Frame: From Day 1 up to 7 days post each dose of study intervention, approximately 14 days ]
	In the report The first occurrence of SARS-CoV-2 symptomatic illness, confirmed by positive results on RT-PCR testing, with onset 15 days or more after the second dose of vaccine or placebo among participants who were seronegative for Covid-19 at baseline
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing stated: Yes Data accessibility: Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca’s data sharing policy described at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure Corresponding author: Dr. Villafana: tonya.villafana@astrazeneca.com
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	Some concerns
General comment	In addition to the published article, the supplementary materials, prospective study registry, and protocol were used in data extraction and risk of bias assessment. The primary efficacy outcome in the article differed slightly from the registry in that first occurrence of symptomatic illness was measured specifically in those who were seronegative at baseline. The primary safety outcomes in the registry were not described as primary outcomes in the article. The target sample size specified in the registry (n=32,459) was nearly achieved (n=32,451). The article reports an early analysis with a cutoff date of March 5, 2021. Follow up for longer term outcomes continues. The study was updated on June 16th, 2022 after publication of additional data on the trial registry website. This study was updated on November 2nd, 2022, after publication of results for a longer follow up.