Covid-19 Living Data

Trial NCT04672395
Publication Bravo L, Lancet, 2022
Dates: 2021-03-24 to 2021-07-19
Funding: Mixed (Clover Biopharmaceuticals; the Coalition for Epidemic Preparedness Innovations; Dynavax Technologies)
Conflict of interest: Yes

Methods
	RCT
	Location : Multicenter / Belgium, Brazil, Colombia, Philippines, South Africa Follow-up duration (months): 4.67
	SCB-2019 (n = 15092) Placebo (n = 15082)
Inclusion criteria	Male or females ≥18 years of age, inclusive willing and able to comply with study requirements, including all scheduled visits, vaccinations, laboratory tests, the electronic completion of the COVID-19 ePRO and other study procedures Healthy adults or adults with pre-existing medical conditions who are in stable condition Female if not pregnant, not breastfeeding, and at least 1 of the following criteria apply: a negative urine pregnancy test prior to each vaccination using a highly effective licensed method of birth control for 30 days prior to the first vaccination and must agree to continue such precautions during the study until 90 days after the second vaccination Individuals (or their legally acceptable representative based on local regulations) willing and able to give an informed consent, prior to screening.
Exclusion criteria	Laboratory-confirmed SARS-CoV-2 infection (e.g., a positive result for the Rapid COVID-19 antigen test) or a known history of SARS-CoV-2 infection behavioral or cognitive impairment (including drug and alcohol abuse) in the opinion of the Investigator any progressive or severe neurologic disorder, seizure disorder, or history of Guillian-Barré syndrome receive treatment with immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, e.g., for cancer or an autoimmune disease, or planned receipt during the study period pregnant, or breastfeeding, or planning to become pregnant during the study period history of severe adverse reaction associated with a vaccine or severe allergic reaction (e.g., anaphylaxis) to any component of the study vaccine history of malignancy within 1 year before screening received any other investigational product within 30 days prior to Day 1 or intent to participate in another clinical study at any time during the conduct of this study have received previous vaccination with any coronavirus vaccine received any other licensed vaccines within 28 days prior to enrollment in this study or who are planning to receive any vaccine up to 14 days after the second vaccination known bleeding disorder that would, in the opinion of the investigator, contraindicate intramuscular injection received any blood/plasma products or immunoglobulins within 60 days prior to Day 1 or plan to receive it during the study period any condition that, in the opinion of the Investigator, may increase the risk of study participation or interfere with the assessment of the primary study objectives fever >37.8°C (≥100.04°F irrespective of method), or any acute illness at baseline (Day 1) or within 3 days of randomization.
Interventions
	Intervention 2 IM doses of 30 mcg SCB-2019 adjuvanted with 1.50 mg CpG-1018 and 0.75 mg alum, 21 days apart
	Control 2 IM doses of placebo, 21 days apart
Participants
	Randomized 30174 participants
	Characteristics of participants Type of participants: Adults N=30174 16009 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: 18-86
	Description of participants Healthy adults or with stable chronic conditions, both SARS-CoV-2 seropositive and seronegative, at 31 centers in Belgium, Brazil, Colombia, Philippines, and South Africa.
Primary outcome
	In the register 1) Number of Participants with a First Occurrence of COVID-19 of Any Severity Starting 14 Days after Second Dose of SCB-2019 [ Time Frame: Day 36 up to Day 389 (1 year after second dose) ]; 2) Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs) [ Time Frame: Up to Day 8 (7 days after first dose) and up to Day 29 (7 days after second dose) ]; 3) Number of Participants with Unsolicited AEs [ Time Frame: Up to Day 43 (21 days after each dose) ]; 4) Number of Participants with Serious Adverse Events (SAEs), or Medically Attended AEs (MAAEs), or AEs Leading to Early Termination, or Adverse Events of Special Interest (AESIs) [ Time Frame: Up to Day 389 (1 year after second dose) ]
	In the report Reactogenicity of the vaccine in an embedded phase 2 study, and the efficacy of SCB-2019 against COVID-19 in participants with no previous exposure to SARS-CoV-2 in the phase 3 study. 1) solicited local reactions and systemic adverse events for 7 days after each injection; 2) any unsolicited adverse events up to study day 43 (14 days after the second dose); 3) Safety is being assessed in an ongoing safety follow-up planned for 12 months after the second vaccination in the safety set that includes any participant who received at least one dose of vaccine or placebo; 4) first occurrence of RT-PCR-confirmed COVID-19 of any severity, with onset at least 14 days after the second vaccination
Documents available	Protocol NR Statistical plan * Data-sharing stated: Yes, Once the study is completed the datasets, including the redacted study protocol, redacted statistical analysis plan, and individual participant data supporting the results reported in this Article, will be available 3 months from the initial request to researchers who provide a methodologically sound proposal, at the discretion of the company governing body. Data accessibility: Correspondence to: Dr Ralf Clemens, clemens.ralf@outlook.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 prospective trial registry and supplementary appendices were used in data extraction and assessment of risk of bias. Neither protocol nor statistical analysis plan was available at the time of data extraction. The article reports an event-driven analysis of data to August 10, 2021, when 248 eligible cases of COVID-19 had been detected. The primary Phase 2 and Phase 3 outcomes reflect those in the registry. The trial (n = 30174) achieved its target sample size (N = 22000). Solicited adverse events were collected in a much smaller (n = 1601) embedded phase 2 subset. Recruitment of adults has been completed. Recruitment of adolescents (12-18 years) continues; adolescents already enrolled in the study at data cut-off were not included in the analysis and will be reported separately.