Trial NCT04368988
Publication Keech C, N Engl J Med, 2020
Dates: 27/05/2020 to 06/06/2020
Funding: Mixed (Novavax/Funded by the Coalition for Epidemic Preparedness Innovations/ vaccine NVX-CoV2373, developed by Novavax and manufactured at Emergent Biosolutions (Rockville,Maryland),)
Conflict of interest: Yes
| Methods | |
| RCT | |
| Location :
Multicenter / Australia Follow-up duration (days): 35 | |
| * | |
| Inclusion criteria | Healthy adult males or females between 18 and 59 years of age, inclusive, at screening. Healthy status will be determined by the investigator based on medical history, clinical laboratory results, vital sign measurements, and physical examination at screening. The subject has a body mass index 17 to 40 kg/m2, inclusive, at screening.Willing and able to give informed consent prior to study enrollment and comply with study procedures. Female subjects of childbearing potential (defined as any female who has experienced menarche and who is NOT surgically sterile [ie, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy] or postmenopausal [defined as amenorrhea at least 12 consecutive months or documented plasma follicle-stimulating hormone level ≥40 mIU/mL]) must agree to be heterosexually inactive from at least 21 days prior to enrollment and through 6 months after the last vaccination OR agree to consistently use any of the following methods of contraception from at least 21 days prior to enrollment and through 6 months after the last vaccination: a.Condoms (male or female) with spermicide (if acceptable in country)b.Diaphragm with spermicide c.Cervical cap with spermicided.Intrauterine device e.Oral or patch contraceptivesf.Norplant®, Depo-Provera®, or other in country regulatory-approved contraceptive method that is designed to protect against pregnancyg.Abstinence, as a form of contraception, is acceptable if in line with the subject’s lifestyle |
| Exclusion criteria | 1.Any ongoing, symptomatic acute or chronic illness requiring medical or surgical care, inclusive of changes in medication in the past 2 months indicating that chronic illness/disease is not stable (at the discretion of the investigator). This includes any current workup of undiagnosed illness that could lead to a new condition.2. Chronic disease inclusive of: a) hypertension uncontrolled for age according to JNC 8 guidelines; b) congestive heart failure by NYHA functional classification of >II; c) chronic obstructive pulmonary disease by GOLD classification of >2; d) recent (within 6 months prior to first study vaccination) exacerbation of coronary artery disease as manifested by cardiac intervention, addition of new cardiac medications for control of symptoms, or unstable angina; e) asthma (diagnosed by spirometry showing reversibility of disease and must meet at least the Step 1 classification with current prescription/use of medications to control symptoms); f) diabetes requiring use of medicine (insulin or oral) or not controlled with diet. 3.Participation in research involving an investigational product (drug/biologic/device) within 45 days prior to first study vaccination. 4.History of a confirmed diagnosis of SARS or COVID-19 disease (confirmed by a specific test for each disease) or known exposure to a SARS-CoV-2 positive confirmed close contact (eg, family member, housemate, daycare provider, aged parent requiring care), at the discretion of the investigator. |
| Interventions | |
| Intervention
Two IM doses 25 µg NVX-CoV2373/0 µg Matrix-M1, 21 days apart Two IM doses 5 µg NVX-CoV2373/50 µg Matrix-M1, 21 days apart Two IM doses 25 µg NVX-CoV2373/50 µg Matrix-M1, 21 days apart One IM dose 25 µg NVX-CoV2373/50 µg Matrix-M1, followed by placebo dose, 21 days apart |
|
| Control
Two IM doses of sterile 0.9% normal saline, 21 days apart | |
| Participants | |
| Randomized * participants | |
| Characteristics of participants Type of participants: Healthy volunteers N=* 64 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: 30.8 Age range: NR | |
| Description of participants Healthy adult volunteers, SARS-CoV-2 infection-free and no history of SARS-CoV-2 infection in two centres in Australia. | |
| Primary outcome | |
| In the register Subjects with solicited AEs - Phase 1;Safety Laboratory Values (serum chemistry, hematology) - Phase 1;Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) - Phase 1 | |
| In the report reactogenicity, safety labs, and immunoglobulin G (IgG) anti-spike protein response. | |
| Documents avalaible |
Protocol Yes. In English Statistical plan Yes Data-sharing stated:
No, These are interim data, and individual participants remain masked to individual vaccine assignment. Therefore, it would be inappropriate to share individual level results at this time |
| 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 report, the protocol, the statistical plan, the registry and supplementary documents were used for the extraction and assessment of bias. This is a report on phases 1/ 2, therefore the total sample size in the register is not achieved. Primary outcome is the same in the registry and the report. As this is an ongoing trial, some secondary outcomes with long time points measurements (e.g;, 217 days, 357 days) are not present in the report. Data for specific and neutralizing antibodies seroconversion events, serconversion rates and antibody titters at day 28 were collected at day 35 (We took the longest observation period). |