Trial NCT04505722
Publication Sadoff J, N Engl J Med, 2022
Funding: Mixed (Janssen Research and Development, and in whole or in part by federal funds from the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, and from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health. )
Conflict of interest: Yes
| Methods | |
| RCT | |
| Location :
Multicenter / Argentina, Brazil, Chile, Colombia, Mexico, Peru, South Africa, USA Follow-up duration (months): 6 | |
| • Ad26.COV2.S (5×10^10 vp), 1 dose (n=22174) • Placebo (0.9% sodium chloride solution), 1 dose (n=22151) |
|
| Inclusion criteria | Stages 1a and 1b: Participant is ≥18 to <60years of age on the day of signing the ICF. Stages 2a and 2b: Participant is ≥60years of age ; BMI <30kg/m2 ; In the investigator’s clinical judgement, participant must be either in good or stable health ; Participants may have underlying illnesses (not associated with increased risk of progression to severe COVID-19a,13 as specified in Exclusion Criterion 15), as long as their symptoms and signs are stable and well-controlled. ; Contraceptive (birth control) use should be consistent with local regulations regarding the acceptable methods of contraception for those participating in clinical studies ; All 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 ; 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 ; Must be willing to provide verifiable identification, has means to be contacted and to contact the investigator during the study ; Must be able to read, understand, and complete questionnaires in the electronic clinical outcome assessment (eCOA) (that is, the coronavirus disease-2019 [COVID 19] signs and symptoms surveillance question, the e-Diary, and the electronic patient-reported outcomes (ePROs). Note: Participants with visual impairment are eligible for study participation and may have caregiver assistance in completing the electronic clinical outcome assessment (eCOA) questionnaires |
| Exclusion criteria | Participant has a clinically significant acute illness (this does not include minor illnesses such as diarrhea or mild upper respiratory tract infection) 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 ; Participant 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 ; Participant previously received a coronavirus vaccine ; Participant received an investigational drug (including investigational drugs for prophylaxis of COVID-19) within 30 days or used an invasive investigational medical device within 30 days or received investigational immunoglobulin or 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 ; Participant has a known or suspected allergy or history of anaphylaxis or other serious adverse reactions to vaccines or their excipients ; Participant has abnormal function of the immune system ; Participant received treatment with Ig in the 3 months or exogenous blood products (autologous blood transfusions are not exclusionary) in the 4 months before the planned administration of the study vaccine or has any plans to receive such treatment during the study ; Participant has a history of an underlying clinically significant acute or chronic medical condition or physical examination findings for which, in the opinion of the investigator, participation would not be in the best interest of the participant ; major psychiatric illness ; comorbidities that are or might be associated with an increased risk of progression to severe COVID-19a,13, ie, participants with moderate to severe asthma; chronic lung diseases such as chronic obstructive pulmonary disease (COPD) (including emphysema and chronic bronchitis), idiopathic pulmonary fibrosis and cystic fibrosis; diabetes (including type 1ortype 2); serious heart conditions, including heart failure, coronary artery disease, congenital heart disease, cardiomyopathies, and pulmonary hypertension; moderate to severe high blood pressure; obesity(body mass index [BMI] ≥30kg/m2); chronic liver disease, including cirrhosis; sickle cell disease; thalassemia; cerebrovascular disease; neurologic conditions (dementia); end stage renal disease; organ transplantation; cancer; HIV infection and other immunodeficiencies; hepatitis B infection; and sleep apnea ; malignancy within 1 year before screening ; surgery requiring hospitalization (defined as inpatient stay for longer than 24 hours or overnight stay), within 12 weeks before vaccination |
| Interventions | |
| Intervention
1 IM dose Ad26.COV2.S (5×10^10 vp) day 0 |
|
| Control
1 IM dose 0.9% sodium chloride solution day 0 | |
| Participants | |
| Randomized 44325 participants | |
| Characteristics of participants Type of participants: Adults N=44325 24053 males Children: 0 Pregnant women: 0 Mean age: 50.7 Age range: 18-100 | |
| Description of participants Adults >18 years of age at 213 centers in Argentina, Brazil, Chile, Colombia, Mexico, Peru, South Africa and USA | |
| Primary outcome | |
| In the register Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical Coronavirus Disease (COVID-19) with Seronegative Status [ Time Frame: 14 Days post-vaccination (Day 15) to end of study (2 years and 1 month) ] Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical Coronavirus Disease (COVID-19) with Seronegative Status [ Time Frame: 28 Days post-vaccination (Day 29) to end of study (2 years and 1 month) ] | |
| In the report Vaccine efficacy against moderate to severe–critical coronavirus disease 2019 (Covid-19) with an onset at least 14 days and at least 28 days after administration among partici-pants in the per-protocol population who had tested negative for SARS-CoV-2. | |
| Variants description | |
| Variants | |
| Description Variant name: Alpha Direct evidence Methods: Prespecified analysis. Exploratory outcome Missing outcome results: 177 cases with no sequence data in the vaccine arm and 210 in the control arm. Variant name: Beta Direct evidence Methods: Prespecified analysis. Exploratory outcome Missing outcome results: 177 cases with no sequence data in the vaccine arm and 210 in the control arm. Variant name: Gamma Direct evidence Methods: Prespecified analysis. Exploratory outcome Missing outcome results: 177 cases with no sequence data in the vaccine arm and 210 in the control arm. Variant name: Delta Direct evidence Methods: Prespecified analysis. Exploratory outcome Missing outcome results: 177 cases with no sequence data in the vaccine arm and 210 in the control arm. | |
| Documents avalaible |
Protocol Yes. In English Statistical plan Yes Data-sharing stated:
Yes, With publication |
| 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 |
Variant beta: Some concerns |
| General comment |
In addition to the FDA Briefing Document, the trial registry and study protocol were used in data extraction and assessment of risk of bias. Data for the outcomes Local adverse events and Systemic adverse events were extracted from the FDA briefing. There were no substantive differences between Briefing Document and the trial registry and study protocol in population, procedures or interventions or outcomes. Some amendments were made to the protocol during the course of the study, including the addition of COVID-19 outcomes at least 28 days after vaccination, in addition to day 14. Some outcomes included in the registry and protocol are not reported, such as mild COVID-19 and immunogenicity in a subset. The study achieved target sample size, which was amended from 60,000 to 40,000. This is an early report of outcomes in a study in which recruitment is completed but follow up continues.
This trial was updated on April 29th, 2021 after publication of the study report and again on March 7th, 2022 after publication of final results. This trial was updated again on June 28th, 2022 after the publication of results on the trial registry website. On Mars 03, 2023 we added a link to a plain language summary. |