Trial NCT04636697
Publication Hager K, N Engl J Med, 2022
Dates: 2021-03-15 to 2021-09-02
Funding: Mixed (Medicago Inc and the governments of Quebec and Canada)
Conflict of interest: Yes
| Methods | |
| RCT | |
| Location :
Multicenter / Argentina, Brazil, Canada, Mexico, UK, USA Follow-up duration (months): 7 | |
| CoVLP+AS03 (n = 12074)
Placebo (n = 12067) |
|
| Inclusion criteria | Study population #1: 18 to 64 years of age, BMI ≥ 18.5 and < 30 kg/m2, in good general health, Female subjects of childbearing potential must have a negative serum pregnancy test result and must use an effective method of contraception; Study population #2: 65 years of age or older, ≥ 18.5 and < 30 kg/m2, non-institutionalized; Study population #3: 18 years of age or older, Female subjects of childbearing potential must have a negative serum pregnancy test result and must use an effective method of contraception, must have one or more co-morbid conditions that puts them at higher risk for severe COVID-19 disease; All populations: reliable and likely to cooperate with the assessment procedures and be available for the duration of the study; Read, understood, and signed the informed consent form. |
| Exclusion criteria | Study Populations #1 and #2: According to the Investigator's opinion, significant acute or chronic, uncontrolled medical or neuropsychiatric illness; any chronic medical condition associated with elevated risk of severe outcomes of COVID-19, including obesity, diabetes (type 1 or type 2), significant cardiovascular or respiratory diseases including asthma, chronic renal failure, disorders of bleeding/coagulation, chronic inflammatory or autoimmune conditions, immunosuppressive conditions (including HIV), and hypertension; confirmed or suspected current immunosuppressive condition or immunodeficiency; autoimmune disease; Administration of any medication or treatment that may alter the vaccine immune responses; Study Population #3: Acute disease defined as presence of any moderate or severe acute illness with or without a fever within 48 hours prior to the Screening. All populations: any vaccine within 14 days prior to Vaccination (Visit 2); planned administration of any vaccine during the study (up to Day 28 of the study). Immunization on an emergency basis during the study will be evaluated on case-by-case basis by the Investigator; any other SARS-CoV-2 / COVID-19, or other experimental coronavirus vaccine at any time prior to or during the study; History of virologically-confirmed COVID-19; Use of any investigational or non-registered product within 30 days or 5 half-lives, whichever is longer, prior to Vaccination (Visit 2) or planned use during the study period; rash, dermatological condition, tattoos, muscle mass, or any other abnormalities at injection site that may interfere with injection site reaction rating; Use of any prescription antiviral drugs with the intention of COVID-19 prophylaxis; serious allergic response to any of the constituents of CoVLP including AS03; documented anaphylactic reactions to plants or plant components (including tobacco, fruits and nuts); Personal or family history of narcolepsy; history of Guillain-Barré Syndrome; positive or doubtful pregnancy test result prior to vaccination or who is lactating; Investigator or employee of the Investigator or clinical site with direct involvement in the proposed study, or identified as an immediate family member. |
| Interventions | |
| Intervention
2 IM doses of 3.75 mcg CoVLP+AS03, 21 days apart |
|
| Control
2 IM doses of placebo, 21 days apart | |
| Participants | |
| Randomized 24141 participants | |
| Characteristics of participants Type of participants: Adults N=24141 12293 males Children: 0 Pregnant women: 0 Immunocompromized patients: 88 Mean age: Age range: 18-82 | |
| Description of participants Adults including elderly with and without comorbidities, with no previous history of virologically confirmed COVID-19, both seronegative and seropositive, at 85 centers in Argentina, Brazil, Canada, Mexico, the UK, and the USA. | |
| Primary outcome | |
| In the register Laboratory-confirmed (virologic method) symptomatic SARS-CoV-2 infection [ Time Frame: Day 28 and after ] First occurrence, in a subject, of laboratory-confirmed (virologic method) symptomatic SARS-CoV-2 infection | |
| In the report Symptomatic SARS-CoV-2 infection seven or more days after receipt of the second dose | |
| Variants description | |
Variants
| |
| Description No dominant variant >50% within study or within countries at the time of the study, variants differed by country and over time - alpha, gamma, delta were common (supp fig 1, data from GISAID, the global data science initiative). Direct evidence VE on VOCs reported, post-hoc analysis. Method: Sequencing of viral genomes from swabs. Missing data: Of the 157 cases included in the per protocol analysis, sequence data are available for 114 (72.6%) and a further 21 (13.4%) could not be sequenced due to very low viral copy numbers. | |
| Documents avalaible |
Protocol Yes. In English Statistical plan Yes Data-sharing stated:
Yes, With publication |
| 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 delta: Some concerns |
| General comment |
In addition to the pre-print article, the trial registry and supplementary appendices were used in data extraction and assessment of risk of bias. A protocol was referred to in the pre-print but was not available at the time of data extraction. The registry reported on phase 2 and 3 whereas the paper reported on phase 3. Consequently, we could not tell if the target sample size was reached. Interventions and outcomes corresponded between report and prospective registry for the phase 3 part, except immunogenicity outcomes that were listed in the registry but not reported in the pre-print. Recruitment to the trial and maintaining of blinding were affected by the widespread roll out of vaccines with emergency use authorizations.
This trial was updated on June 20th, 2022 after publication of the study report. |