Trial NCT04636697
Publication Gobeil P, medRxiv, 2021
Dates: 2020-11-25 to 2021-03-24
Funding: Private (Medicago Inc)
Conflict of interest: Yes
Methods | |
RCT | |
Location :
Multicenter / Canada, USA Follow-up duration (months): 1.4 | |
3.75 mcg CoVLP adjuvanted vaccine (n=632) Placebo (n=121) |
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Inclusion criteria | For both Healthy Adults and Older Adults, subjects must have been in good general health with no clinically relevant abnormalities that could jeopardize subject safety or interfere with study assessments, as determined by medical history, physical examination, and vital signs, and have had a body mass index less than 30 kg/m2. Adults with Comorbidities included subjects with one or more comorbid conditions that puts them at higher risk for severe COVID-19 such as obesity, hypertension, type 1 or type 2 diabetes, chronic obstructive pulmonary disease (COPD), cardiovascular diseases, chronic kidney diseases, or a compromised immune system (eg, treatment-controlled HIV infection, organ transplant recipients, or patients receiving cancer chemotherapy). Female subjects of childbearing potential must have had a negative pregnancy test result at screening and vaccination and used a highly effective method of contraception for one month prior to vaccination and at least one month after the last study vaccination. |
Exclusion criteria | Exclusion criteria for Healthy Adults and Older Adults included i) any significant acute or chronic, uncontrolled medical or neuropsychiatric illness, ii) any chronic medical condition associated with elevated risk of severe outcome of COVID-19, iii) any confirmed or suspected current immunosuppressive condition or immunodeficiency, including cancer, HIV, hepatitis B or C infection, iv) current autoimmune disease, v) administration of any medication or treatment that could alter the vaccine immune response. In all three study populations exclusion criteria also included vi) administration of any vaccine within 14 days prior to vaccination or planned administration of any vaccine up to Day 28 of the study, vii) administration of any other SARS-CoV-2 / COVID-19, or other experimental coronavirus vaccine at any time prior to or during the study, viii) history of virologically-confirmed COVID-19, ix) rash, dermatological condition, tattoos, muscle mass, or any other abnormalities at injection site that could interfere with injection site reaction rating, x) use of prophylactic medications (eg, antihistamines [H1 receptor antagonists], nonsteroidal anti-inflammatory drugs [NSAIDs], systemic and topical glucocorticoids, non-opioid and opioid analgesics) within 24 hours prior to the vaccination to prevent or pre-empt symptoms due to vaccination, xi) history of a serious allergic response to any of the constituents of CoVLP, including AS03, xii) history of documented anaphylactic reaction to plants or plant components (including tobacco, fruits and nuts), xiii) personal or family (first-degree relatives) history of narcolepsy, xiv) history of Guillain-Barré Syndrome. Sentinel subjects (10 in each group) were first enrolled in Older Adults and Adults with Comorbidities groups, and unblinded safety data after each dose were reviewed by the IDMC. Enrollment into the Phase 2 portion of the study was closed on 25 March 2021. |
Interventions | |
Intervention
2 IM doses of 3.75 mcg CoVLP, 21 days apart |
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Control
2 IM doses of placebo, 21 days apart | |
Participants | |
Randomized 753 participants | |
Characteristics of participants Type of participants: Healthy adults, adults with comorbidities and older adults N=753 357 males Children: 0 Pregnant women: 0 Mean age: Age range: 18-88 | |
Description of participants Healthy adults, adults with comorbidities, non-institutionalized older adults (seronegative and seropositive) in multiple centers in Canada and the USA | |
Primary outcome | |
In the register Immediate adverse event (AEs) [ Time Frame: 30 minutes ]; Solicited local and systemic adverse events (AEs) [ Time Frame: 7 days]; Unsolicited adverse events (AEs) [ Time Frame: 21 days ]; Number of subjects with normal and abnormal clinically significant urine values [ Time Frame: 3 days ]; Number of subjects with normal and abnormal clinically significant haematological values [ Time Frame: 3 days ]; Number of subjects with normal and abnormal clinically significant biochemical values [ Time Frame: 3 days ]; Percentage of subjects with normal and abnormal clinically significant urine values [ Time Frame: 3 days ]; Percentage of subjects with normal and abnormal clinically significant haematological values [ Time Frame: 3 days ]; Percentage of subjects with normal and abnormal clinically biochemical values [ Time Frame: 3 days ]; Serious adverse events (SAEs), adverse events (AEs) leading to withdrawal, adverse event of special interest (AESI) (including vaccine-enhanced disease) and deaths [ Time Frame: 21 days ]; Neutralizing antibody (Nab assay) response [ Time Frame: Day 21 ]; Neutralizing antibody (Nab assay) response [ Time Frame: Day 42 ]; Specific Th1 cell-mediated immunity (CMI) response [ Time Frame: Day 21 ]; Specific Th1 cell-mediated immunity (CMI) response [ Time Frame: Day 42 ] | |
In the report Primary safety outcomes were the occurrence(s) of i) immediate AEs within 30 minutes after each vaccination; ii) solicited local and systemic AEs up to 7 days after each vaccination; iii) unsolicited AEs, serious AEs (SAEs), AEs leading to withdrawal, AEs of special interest (AESIs), and deaths up to 21 days after each vaccination; iv) normal and abnormal urine, haematological, and biochemical values. Primary immunogenicity outcomes were i) neutralizing antibody (NAb) titers measured using a pseudovirion neutralization assays and ii) interferon (IFN)-γ and IL-4 ELISpot responses at 21 days after each dose of vaccine. | |
Variants description | |
Variants | |
Description | |
Documents avalaible |
Protocol NR Statistical plan * Data-sharing stated:
Yes, At the end of the clinical trial, which is currently scheduled to be 1 year after the last participant is enrolled, unless granted an extension |
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 |
* |
General comment | In addition to the pre-print article, the prospective study registry was used in data extraction and risk of bias assessment. Neither protocol nor statistical analysis plan was available. There were no substantive differences between the pre-print article and the registry in population, procedures, interventions or outcomes. The pre-print reported on an interim analysis for phase 2 of an ongoing phase 2/3 study. The safety and immunogenicity data collected at later timepoints will be released once study follow-up has been completed. No outcomes were reported in a format that could be extracted for the review, pending contact with authors. |