Covid-19 Living Data

Trial NCT04614948
Publication Hardt K, Lancet Infect Dis, 2022

Funding: Mixed (Janssen Vaccines & Prevention B.V.; Biomedical Advanced Research and Development Authority, part of the Office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services (HHS); National Institute of Allergy and Infectious Diseases (NIAID), NIH)
Conflict of interest: Yes

Methods
	RCT
	Location : Multicenter / Belgium, Brazil, Colombia, France, Germany, The Philippines, South Africa, Spain, UK, USA Follow-up duration (months): 7.4
	Ad26.COV2.S/Ad26.COV2.S (n = 15,708 received at least 1 vaccine) Placebo (n = 15,592 received at least 1 injection)
Inclusion criteria	Informed consent ≥18 years of age in good health or with underlying illnesses that were stable and well-controlled either not of childbearing potential or of childbearing potential and practicing an acceptable effective method of contraception negative pregnancy test on the day of and prior to each study vaccine administration agreed to not donate bone marrow, blood, and blood products until 3 months after the last dose of the study vaccine
Exclusion criteria	Clinically significant acute illness or temperature greater than or equal to 38.0 degree Celsius (100.4-degree Fahrenheit) within 24 hours prior to the planned first dose of study vaccine, randomization at a later date is permitted at the discretion of the investigator and after consultation with the sponsor known or suspected allergy or history of anaphylaxis or other serious adverse reactions to vaccines or their excipients received or plans to receive: (a) licensed live attenuated vaccines - within 28 days before or after planned administration of study vaccine and (b) other licensed (not live) vaccines - within 14 days before or after planned administration of study vaccine previously received a coronavirus vaccine received an investigational drug within 30 days (including investigational drugs for prophylaxis of COVID-19) or used an invasive investigational medical device within 30 days or received investigational immunoglobulin (Ig) or investigational monoclonal antibodies within 3 months, or received convalescent serum for COVID-19 treatment within 4 months or received an investigational vaccine (including investigational Adenoviral-vectored vaccines) within 6 months before the planned administration of the first dose of study vaccine or is currently enrolled or plans to participate in another investigational study during the course of this study
Interventions
	Intervention 2 IM 5.5×10^10 vp doses of Ad26.COV2.S, 56 days apart
	Control 2 IM doses of saline placebo, 56 days apart
Participants
	Randomized 31835 participants
	Characteristics of participants Type of participants: Adults N=31835 16474 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: 18-99
	Description of participants Adults, healthy or with stable and well-controlled comorbidities, at 125 centers in Belgium, Brazil, Colombia, France, Germany, The Philippines, South Africa, Spain, UK, and USA
Primary outcome
	In the register Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 and who were Seronegative at Baseline [ Time Frame: At least 14 days after the second vaccination (Day 71) to end of study (2 years and 3 months) ]
	In the report Vaccine efficacy against the first occurrence of molecularly-confirmed moderate to severe–critical Covid-19 with onset ≥14 days after booster vaccination in the per-protocol population
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing stated: Yes Data accessibility: The data sharing policy of Janssen Pharmaceutical Companies of Johnson & Johnson is available at https://www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at http://yoda.yale.edu. Corresponding Author: Frank Struyf, M.D.; Email: FStruyf@ITS.JNJ.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 pre-print article, the supplementary materials and study registry were used in data extraction and risk of bias assessment. Neither protocol nor statistical analysis plan was available. The primary outcome in the article reflects that in the registry. The article reports analysis of the blinded section of the trial; after licensing of vaccines, those who received placebo were unblinded and allowed to receive a second vaccine, including crossing over to other vaccines; follow up continues. Vaccine effectiveness evaluated per protocol in seronegative participants with no major protocol violations. This trial was updated on November 2nd, 2022, after publication of the study report.