Trial NCT04537208
Publication Goepfert P, Lancet, 2021
Dates: 2020-09-03 to 2020-09-29
Funding: Mixed (Sanofi Pasteur and Biomedical Advanced Research and Development Authority (BARDA))
Conflict of interest: Yes
| Methods | |
| RCT | |
| Location :
Multicenter / USA Follow-up duration (months): 1.4 | |
| • 1.3 mcg CoV2 preS dTM + AFO3 (n=28) • 1.3 mcg CoV2 preS dTM + ASO3 (n=84) ) • 2.6 mcg CoV2 preS dTM + AFO3 (n=27) ) • 2.6 mcg CoV2 preS dTM + AS03 (n=85) ) • 2.6 CoV2 preS dTM (n=18) ) • Placebo (n=29) |
|
| Inclusion criteria | Healthy adults; 18 years and older; testing negative for SARS-CoV-2 antibodies |
| Exclusion criteria | Chronic illness or medical conditions considered to potentially increase the risk for severe Covid-19 illness; women who were pregnant or lactating; women of childbearing potential who were not using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until at least 12 weeks after the last vaccination; participation, or planned participation, in another clinical trial during the study period; receipt or planned receipt of any vaccine in the 30 days before the first or up to 30 days following the last study vaccination (except for influenza vaccination, which may be received at least 2 weeks before or after study vaccines); receipt of immunoglobulins, blood or blood-derived products in the past 3 months; and active or prior documented autoimmune disease. |
| Interventions | |
| Intervention
2 IM doses of 1.3 mcg CoV2 preS dTM + AFO3 adjuvant, 21 days apart 2 IM doses of 1.3 mcg CoV2 preS dTM + ASO3 adjuvant, 21 days apart 2 IM doses of 2.6 mcg CoV2 preS dTM + AFO3 adjuvant, 21 days apart 2 IM doses of 2.6 mcg CoV2 preS dTM + ASO3 adjuvant, 21 days apart 2 IM doses of 2.6 mcg CoV2 preS dTM, 21 days apart |
|
| Control
2 IM doses NaCl, 21 days apart | |
| Participants | |
| Randomized 441 participants | |
| Characteristics of participants Type of participants: Healthy volunteers N=441 133 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: NR | |
| Description of participants Health adults aged 18 years and older and SARS-CoV-2 infection-free in 10 centres in the USA. | |
| Primary outcome | |
| In the register 1. Neutralizing Antibody Titer at Day 1 [ Time Frame: Day 1 ] 2. Neutralizing Antibody Titer at Day 22 [ Time Frame: Day 22 ] 3. Neutralizing Antibody Titer at Day 36 [ Time Frame: Day 36 ] 4. Fold-rise of Neutralizing Antibody Titer at Day 22 [ Time Frame: Day 22 ] 5. Fold-rise of Neutralizing Antibody Titer at Day 36 [ Time Frame: Day 36 ] 6. 2-fold and 4-fold Rise in Neutralization Antibody titer at Day 22 [ Time Frame: Day 22 ] 7. 2-fold and 4-fold Rise in Neutralization Antibody titer at Day 36 [ Time Frame: Day 36 ] 8. Percentage of Participants with Neutralizing Antibody Seroconversion at Day 22 [ Time Frame: Day 22 ] 9. Percentage of Participants with Neutralizing Antibody Seroconversion at Day 36 [ Time Frame: Day 36 ] 10. Number of Participants with Immediate Adverse Events [ Time Frame: Within 30 minutes after vaccination ] 11. Number of Participants With Solicited Injection Site or Systemic Reactions [ Time Frame: Within 7 days after vaccination ] 12. Number of Participants with Unsolicited Adverse Events [ Time Frame: Within 21 days after vaccination ] 13. Number of Participants with Medically Attended Adverse Events [ Time Frame: From Day 1 up to the end of study (Day 366 for Cohort 1 and Day 387 for Cohort 2) ] 14. Number of Participants with Serious Adverse Events (SAEs) [ Time Frame: From Day 1 up to the end of study (Day 366 for Cohort 1 and Day 387 for Cohort 2) ] 15. Number of Participants with Adverse Events of Special Interest [ Time Frame: From Day 1 up to the end of study (Day 366 for Cohort 1 and Day 387 for Cohort 2) ] | |
| In the report 1. The primary objective was to describe the safety profile of the candidate vaccine formulations in all participants. 2. The primary immunogenicity objective was to describe the neutralising capacity of vaccine-induced antibodies at D1, D22 and D36 for each study group. | |
| Variants description | |
| Variants | |
| Description | |
| Documents avalaible |
Protocol Yes. In English Statistical plan Yes Data-sharing stated:
Yes |
| 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 trial registry and the protocol were used in data extraction and assessment of risk of bias. The publication reports an interim analysis (safety and immunogenicity outcomes) including 439 randomized participants. Data for those assigned to the two-dose arms were collected; single dose data were not collected. The study did not calculate sample size a priori. Due to an error, the planned 5 mcg and 15 mcg of functional SARS-CoV-2 preS protein per dose were significantly lower (1.3 mcg and 2.6 mcg). |