Covid-19 Living Data

Trial NCT04611802
Publication Dunkle L M, N Engl J Med, 2021
Dates: 2020-12-27 to 2021-02-18
Funding: Mixed (Funded by Novavax and the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health)
Conflict of interest: Yes

Methods
	RCT
	Location : Multicenter / Mexico, USA Follow-up duration (months): 2
	NVX-CoV2373 (n = 19965) Placebo (n = 9984)
Inclusion criteria	Adults ≥ 18 years of age considered at substantial risk of exposure to and infection with SARS-CoV-2 informed consent Participants of childbearing potential must agree to be heterosexually inactive OR agree to consistently use a medically acceptable method of contraception from at least 28 days prior to enrollment and through 3 months after the last vaccination medically stable, as determined by the investigator (based on review of health status, vital signs [to include body temperature], medical history, and targeted physical examination [to include body weight]) Agree to not participate in any other SARS-CoV-2 prevention trial during the study follow-up.
Exclusion criteria	Unstable acute or chronic illness Participation in research involving an investigational product (drug/biologic/device) within 45 days prior to first study vaccination History of a previous laboratory-confirmed diagnosis of SARS-CoV-2 infection or COVID-19 Received influenza vaccination or any other adult vaccine within 4 days prior to or within 7 days after either study vaccination. Received any vaccine within 4 days prior to first study vaccination or planned receipt of any vaccine before Day 49 (ie, 28 days after second vaccination) Autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) requiring ongoing immunomodulatory therapy Chronic administration (defined as > 14 continuous days) of immunosuppressant, systemic glucocorticoids, or other immune-modifying drugs within 90 days prior to first study vaccination Received immunoglobulin, blood-derived products, or immunosuppressant drugs within 90 days prior to first study vaccination Active cancer (malignancy) on therapy within 1 year prior to first study vaccination (with the exception of malignancy cured via excision, at the discretion of the investigator) Any known allergies to products contained in the investigational product Participants who are breastfeeding, pregnant or who plan to become pregnant within 3 months following last study vaccination Any other condition that, in the opinion of the investigator, would pose a health risk to the participant if enrolled or could interfere with evaluation of the trial vaccine or interpretation of study results Study team member or first-degree relative of any study team member (inclusive of Sponsor, and study site personnel involved in the study) Current participation in any other COVID-19 prevention clinical trial.
Interventions
	Intervention 2 doses of 5 mcg in 0.5 mL, 21 days apart
	Control 2 doses of placebo, 21 days apart
Participants
	Randomized 29949 participants
	Characteristics of participants Type of participants: Adults N=29949 13181 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: 18-95
	Description of participants Healthy adults in 113 sites in the USA and 6 in Mexico
Primary outcome
	In the register Participants with Symptomatic Mild, Moderate, or Severe Coronavirus Disease 2019 (COVID-19) [ Time Frame: Day 28 to Day 750 ]
	In the report First episode of reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed symptomatic mild, moderate, or severe Covid-19 (using FDA criteria) with onset ≥7 days after the second injection
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing stated: Yes, With publication Data accessibility: https://clinicaltrials.gov/ct2/show/NCT04611802 Lisa M. Dunkle, M.D: LDunkle@novavax.com.
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 protocol, statistical plan, trial registry and supplementary appendices were used in data extraction and assessment of risk of bias. Neither protocol nor statistical analysis plan was available. The primary outcome in the article reflects that in the registry. The article reports early analyses to April 2021, at which the median follow up was 2 months. Subsequently participants in the placebo arm were able to receive a licensed vaccine. Follow up continues. This trial was updated on Mars 1st, 2022 after the publication of the study report.