Covid-19 Living Data

Trial NCT04436276
Publication Sadoff J, N Engl J Med, 2021
Dates: 22/07/2020 to 24/08/2020
Funding: Mixed (This project was sponsored by Johnson and Johnson and funded, in part, by the Department of Health and Human Services Biomedical Advanced Research and Development Authority)
Conflict of interest: Yes

Methods
	RCT
	Location : Multicenter / Belgium, USA Follow-up duration (months): 2.33
	≥18 to ≤55 years (Cohort 1a) • Ad26.COV2.S 5×1010 vp (n = 153) • Ad26.COV2.S 1×1010 vp (n = 150) • Placebo 1 (n = 77) ≥18 to ≤55 years (Cohort 1b) • Ad26.COV2.S 5×1010 vp (n = 10) • Ad26.COV2.S 1×1010 vp (n = 10) • Placebo 1 (n = 5) ≥65 years (Cohort 3) • Ad26.COV2.S 5×1010 vp (n = 161) • Ad26.COV2.S 1×1010 vp (n = 162) • Placebo 2 (n = 82) At the time of this analysis, enrollment of Cohort 2 had not started.
Inclusion criteria	1. Participant must sign an informed consent form (ICF) indicating that he or she understands the purpose, procedures, and potential risks and benefits of the study, and is willing to participate in the study 2. All female participants of childbearing potential must have a negative highly sensitive urine pregnancy test at screening and have a negative highly sensitive urine pregnancy test immediately prior to each study vaccine administration 3. Participant must have a body mass index (BMI) less than or equal to (<=) 30.0 kilograms per squaremeter (kg/m^2) 4. Applicable to Cohorts 1 and 2 only: Participant must be healthy, in the investigator's clinical judgment,as confirmed by medical history, physical examination, clinical laboratory assessments, and vital signs performed at screening, and must not have comorbidities related to an increased risk of severe coronavirus disease-2019 (COVID-19). Applicable to Cohort 3 only: In the investigator's clinical judgment, participant must be either in good or stable health Participants may have underlying illnesses such as hyperlipoproteinemia or hypothyroidism, as long as their symptoms and signs are medicallycontrolled and not considered to be comorbidities related to an increased risk of severe COVID-19 (participants may have medical conditions of mild severity (according to the Toxicity Grading Scale),including hypertension or high blood pressure, as long as their symptoms and signs are stable and medically controlled as defined by no change in medication over the past 6 months [except for issues of tolerability or use of similar drug with same mechanism of action, for example, thiazides, Beta blockers, Alpha blockers at the same effective dose]). If they are on medication for a condition, the medication dose must have been stable for at least 12 weeks preceding vaccination and expected to remain stable for the duration of the study. Participants will be included on the basis of physical examination, clinical laboratory assessments medical history, and vital signs (participants can be enrolled with Grade 1 or Grade 2 values for vital signs measurements) 5. Participant agrees to not donate bone marrow, blood, and blood products from the first study vaccine administration until 3 months after receiving the last dose of study vaccine
Exclusion criteria	1. Participant has a clinically significant acute illness (this does not include minor illnesses such asdiarrhea or mild upper respiratory tract infection) or temperature greater than or equal to (>=) 38.0degree Celsius within 24 hours prior to the planned first dose of study vaccine randomization at a laterdate is permitted at the discretion of the investigator and after consultation with the sponsor 2. Participant has a history of malignancy within 5 years before screening (exceptions are squamous andbasal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is consideredcured with minimal risk of recurrence) 3. Participant has a history of any neurological disorders or seizures including Guillain-Barre syndrome,with the exception of febrile seizures during childhood 4. Participant has a positive diagnostic test result for SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) at screening 5. Participants with comorbidities that are or might be associated with an increased risk of progression tosevere COVID-19, that is, participants with moderate-to-severe asthma chronic lung diseases such aschronic obstructive pulmonary disease (COPD) (including emphysema and chronic bronchitis),idiopathic pulmonary fibrosis and cystic fibrosis diabetes (including type 1, type 2, or gestational) serious heart conditions, including heart failure, coronary artery disease, congenital heart disease,cardiomyopathies, and (pulmonary) hypertension or high blood pressure obesity (BMI >= 30 kg/m^2) chronic kidney disease being treated with dialysis participants who are immunocompromised (asoutlined in other exclusion criteria) chronic liver disease, including cirrhosis sickle cell disease thalassemia cerebrovascular disease neurologic conditions (dementia) smoking and participants who live in nursing homes or long-term care facilities. Investigators must refer to the complete list of conditions that increase the risk of progression to severe COVID-19 available at the Centers forDisease Control and Prevention (CDC) website. Applicable to Cohort 3 only: Participants may have medical conditions of mild severity (according to the Toxicity Grading Scale), including hypertension or high blood pressure, as long as their symptoms and signs are stable and medically controlled in the judgment of the investigator 6. Applicable to Cohorts 1 and 3 only: Participant currently working in an occupation with a high risk of exposure to SARS-CoV-2 (for example, health care worker or emergency response personnel) or considered at the investigator's discretion to be at increased risk to acquire COVID-19 for any other reason
Interventions
	Intervention 1 or 2 IM low dose of 5x10^10 vp Ad26.COV2.S 56 days apart 1 or 2 IM high dose of 1x10^11 vp Ad26.COV2.S 56 days apart
	Control 1 or 2 IM dose of saline placebo 56 days apart
Participants
	Randomized 810 participants
	Characteristics of participants Type of participants: Healthy volunteers N=810 391 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: NR Age range: 18-83
	Description of participants Healthy SARS-CoV-2 nucleic acid negative adults 18-55 years old and elderly >65 years old in multiple centres in Belgium and the US
Primary outcome
	In the register Number of Participants with Solicited Local Adverse Events (AEs) for 7 Days after First and Second Vaccination; Number of Participants with Solicited Systemic AEs for 7 Days after First and Second Vaccination; Number of Participants with Unsolicited AEs for 28 Days after First and Second Vaccination; Number of Participants with Serious Adverse Events (SAEs) from the FirstVaccination until 1 Year after the Second Vaccination
	In the report The primary end points were the safety and re-actogenicity of each dose schedule. Follow-up visits to evaluate reactogenicity, safety, and im-munogenicity were scheduled on days 7, 28, and 71 after vaccination in each cohort.
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing stated: No Data accessibility: NR
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	Low
General comment	In addition to the preprint, the study registry and the protocol were used in data extraction and risk of bias assessment. Interim safety results after the first dose in a two-dose schedule from an ongoing study were reported. Interim immunologic results were available for one cohort and not all the participants were analyzed. There is no change from the protocol in the intervention and control treatments. The primary outcome indicated in the protocol for phase I reflects the primary outcome reported in the paper.