Covid-19 Living Data

Trial NCT04283461; NCT04785144
Publication Anderson E, SSRN, 2022
Dates: 2021-03-29 to 2021-04-30
Funding: Mixed (Infectious Diseases Clinical Research Consortium through the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, under award number UM1AI148684, and by award numbers UM1AI148373 (Kaiser Washington), UM1AI148576 (Emory University), and HHSN272201500002C (Emmes). Moderna, Inc. provided mRNA-1273 and mRNA-1273.351 for the booster vaccinations and some authors are Moderna employees.)
Conflict of interest: Yes

Methods
	RCT
	Location : Multicenter / USA Follow-up duration (months): 1
	100 mcg of mRNA-1273 (n=48) / 50 mcg of mRNA-1273.351 (n=25) 25 mcg of mRNA-1273.351 and 25 mcg of mRNA-1273 (n=23)
Inclusion criteria	Provides written informed consent prior to initiation of any study procedures Be able to understand and agrees to comply with planned study procedures and be available for all study visits Agrees to the collection of venous blood per protocol. Cohort 1: previously received 2 doses of mRNA-1273 intramuscular (IM) as part of DMID 20-0003 Cohort 1: Male or non-pregnant female, >/= 18 years of age at time of enrollment. Cohort 2: Male or non-pregnant female, 18 through 55 years of age at time of enrollment Women of childbearing potential* must agree to practice abstinence or use at least one acceptable primary form of contraception., * Note: These criteria are applicable to females in a heterosexual relationship and child-bearing potential (i.e., the criteria do not apply to subjects in a same sex relationship) In good health Oral temperature is less than 100.0 degrees Fahrenheit (37.8 degrees Celsius) Must agree to have samples stored for secondary research Agrees to adhere to Lifestyle Considerations throughout study duration Must agree to refrain from donating blood or plasma during the study (outside of this study).
Exclusion criteria	Positive pregnancy test prior to each vaccine administration BMI > 40.0 kg / m^2 Female subject who is breastfeeding Has any medical disease or condition that, in the opinion of the participating site PI or appropriate sub-investigator, precludes study participation Presence of self-reported or medically documented significant medical or psychiatric condition(s) Has an acute illness, as determined by the participating site PI or appropriate sub-investigator, with or without fever [oral temperature >/= 38.0 degrees Celsius (100.4 degrees Fahrenheit)] within 72 hours prior to each vaccination Has participated in another investigational study involving any investigational product within 5 half-lives before the first vaccine administration Currently enrolled in or plans to participate in another clinical trial with an investigational agent* that will be received during the study-reporting period Has a history of hypersensitivity or severe allergic reaction (e.g., anaphylaxis, generalized urticaria, angioedema, other significant reaction) to drugs or any previous licensed or unlicensed vaccines or to polyethylene glycol (PEG) or a PEG-containing product Chronic use (more than 14 continuous days) of any medications that may be associated with impaired immune responsiveness Anticipating the need for immunosuppressive treatment within the next 6 months Received immunoglobulins and/or any blood or blood products within the 4 months before the first vaccine administration or at any time during the study Has any blood dyscrasias or significant disorder of coagulation Received or plans to receive a licensed, live vaccine within 4 weeks before or after each vaccination Received or plans to receive a licensed, inactivated vaccine within 2 weeks before or after each vaccination Receipt of any other SARS-CoV-2 vaccine or any experimental coronavirus vaccine at any time prior to or during the study, except Cohort 1 subjects who received mRNA-1273 in DMID 20-0003. Close contact of anyone known to have SARS-CoV-2 infection within 14 days prior to vaccine administration History of COVID-19 diagnosis, positive SARS-CoV-2 PCR test, or, for Cohort 2 only, a known positive SARS-CoV-2 serologic test On current treatment with investigational agents for prophylaxis of COVID-19.
Interventions
	Intervention 1 IM dose of 100 mcg mRNA-1273 1 IM dose of 50 mcg mRNA-1273.351
	Control 1 IM dose of 25 mcg mRNA-1273.351 and 25 mcg mRNA-1273
Participants
	Randomized 96 participants
	Characteristics of participants Type of participants: Healthy volunteers N=96 50 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: 18-71+
	Description of participants Healthy adult volunteers who were SARS-CoV-2 infection-free in 3 sites in the USA
Primary outcome
	In the register Frequency of any medically-attended adverse events (MAAEs) [ Time Frame: Day 1 to day 422 ] Frequency of any new-onset chronic medical conditions (NOCMCs) [ Time Frame: Day 1 to day 422 ] Frequency of any protocol specified adverse events of special interest (AESIs) [ Time Frame: Day 1 to day 422 ] Frequency of any serious adverse events (SAEs) [ Time Frame: Day 1 to day 422 ] Frequency of solicited reactogenicity adverse events (AEs) [ Time Frame: Through 7 days post-vaccination ] Both local and systemic AEs will be assessed. Frequency of unsolicited adverse events (AEs) [ Time Frame: Through 28 days post-vaccination ] Grade of solicited reactogenicity adverse events (AEs) [ Time Frame: Through 7 days post-vaccination ] Both local and systemic AEs will be assessed. Grade of unsolicited adverse events (AEs) [ Time Frame: Through 28 days post-vaccination ]
	In the report Safety and immunogenicity after a third mRNA vaccination
Documents available	Protocol NR Statistical plan * Data-sharing stated: NR Data accessibility: A data sharing statement provided by the author is available with the full text of this article at NEJM.org; Evan Anderson, evanderson@emory.edu
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 pre-print article, the supplementary appendix and prospective study registry were used in data extraction and risk of bias assessment. The protocol and statistical analysis plan were not available. This is an interim analysis at 28 days of a study with ongoing follow up. The 100 mcg intervention arm was reported in the study but not in the registry. The target sample size specified in the registry for the other two arms (n=60) was not achieved (n=48).