Trial NCT04526990
Publication Halperin SA, Lancet, 2021
Dates: 2020-09-22 to 2021-03-15
Funding: Private (CanSino Biologics and the Beijing Institute of Biotechnology)
Conflict of interest: Yes
| Methods | |
| RCT | |
| Location :
Multicenter / Argentina, Chile, Mexico, Pakistan, Russia Follow-up duration (months): * | |
| Ad5-nCoV (n= 18493) Placebo (n= 18489) | |
| Inclusion criteria | 18 years or older; no unstable or severe underlying medical or psychiatric conditions; no history of a laboratory-confirmed SARS-CoV-2 infection; no previous receipt of an adenovirus-vectored, coronavirus, or SARS-CoV-2 vaccine; able to understand the content of the informed consent form and provide written consent; a negative pregnancy test was required for all women of childbearing potential before immunisation; participants involved in heterosexual sexual activity had to agree to the use of approved contraceptive methods |
| Exclusion criteria | Participation in any other COVID-19 prophylactic drug trials for the duration of the study; Participation in SARS-CoV-2 serological surveys where participants are informed of their serostatus for the duration of the study; Planned receipt of any vaccine (licensed or investigational), other than the study intervention, within 14 days before and after study vaccination; Prior receipt of an investigational or licensed vaccine likely to impact on the interpretation of the trial data (e.g. Adenovirus vectored vaccines, any coronavirus or SARS vaccines); Administration of immunoglobulins and/or any blood products within the three months prior to the planned administration of the vaccine candidate; Any confirmed or suspected immunosuppressive or immunodeficient state; positive HIV status; asplenia; recurrent severe infections and chronic use (more than 14 days) of immunosuppressant medication within the past 6 months. Topical steroids or short-term (course lasting ≤14 days) oral steroids are not an exclusion; History of allergic disease or reactions likely to be exacerbated by any component of Ad5- nCoV; Any history of angioedema; Pregnancy, lactation or willingness/intention to become pregnant within 90 days after receiving study vaccine; Current diagnosis of or treatment for 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 venepuncture; Suspected or known current alcohol or drug dependency; Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder and neurological illness (mild/moderate well-controlled comorbidities are allowed); History of laboratory-confirmed COVID-19; Continuous use of anticoagulants, such as coumarins and related anticoagulants (i.e., warfarin) or novel oral anticoagulants (i.e., apixaban, rivaroxaban, dabigatran and edoxaban); Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data |
| Interventions | |
| Intervention
1 IM Ad5-nCoV vaccine standard (5×10¹⁰ vp) dose |
|
| Control
1 IM dose placebo | |
| Participants | |
| Randomized 36982 participants | |
| Characteristics of participants Type of participants: Healthy adults N=36982 24241 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: 18.0-91.5 | |
| Description of participants Healthy adults with no history of laboratory-confirmed COVID-19 at 66 sites in Argentina, Chile, Mexico, Pakistan, and Russia | |
| Primary outcome | |
| In the register 1) Incidence of COVID-19 cases [ Time Frame: day 28 to 12 months post vaccination ] The efficacy of Ad5-nCoV in preventing virologically confirmed (PCR positive) COVID-19 disease; 2) Incidence of SAE [ Time Frame: Within 12 months ] Evaluate the incidence of severe adverse events (SAE) | |
| In the report 1) incidence of serious adverse events and medically attended adverse events after vaccination; 2) prevention of symptomatic, real-time PCR-confirmed COVID-19 infection occurring 28 days after vaccination | |
| Variants description | |
Variants
| |
| Description Most PCR-confirmed COVID-19 cases accrued in Mexico and Pakistan; throughout the study period for this analysis, the B.1.1.519 variant predominated throughout Mexico, and in Pakistan, in the last 4 weeks before reaching the study endpoint, nearly one-third of the sequenced isolates were the alpha variant, and the remainder were the ancestral strain | |
| Documents avalaible |
Protocol Yes. In English Statistical plan Yes Data-sharing stated:
Yes, De-identified individual participant data will be made available after 9 months and until 36 months following completion of the final study report |
| 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 study registry and protocol were used in data extraction and risk of bias assessment. The efficacy outcomes were assessed using an interim analysis where participants were still being recruited at data cut-off. The study enrolled a full safety cohort, per-protocol efficacy cohort, a smaller safety cohort for close monitoring of solicited adverse events, and a smaller immunogenicity cohort - all pre-planned. There were no important differences between protocol/registry and published report in population, procedures, interventions or outcomes. |