Covid-19 Living Data

Trial NCT04762680
Publication Sridhar S, Lancet Infect Dis , 2022
Dates: 2021-02-24 to 2021-03-08
Funding: Mixed (Sanofi Pasteur + Biomedical Advanced Research and Development Authority (BARDA))
Conflict of interest: Yes

Methods
	RCT
	Location : Multicenter / USA, Honduras Follow-up duration (months): 1.4
	5 mcg (low dose) CoV2 preS dTM (n=241) 10 mcg (medium dose) CoV2 preS dTM (n=239) 15 mcg (high dose) CoV2 preS dTM (n=242)
Inclusion criteria	Adults aged 18 years and older individuals with pre-existing medical conditions, those who were immunocompromised (except those with recent organ transplant or chemotherapy) and those with a potentially increased risk for severe COVID-19, were eligible for participation in the study
Exclusion criteria	Women who were pregnant or lactating, or, for those of childbearing potential, not using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until at least 12 weeks after the last vaccination known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to a vaccine containing any of the same substances dementia or any other cognitive condition at a stage that could interfere with following the trial procedures based on Investigator or designee's judgment self-reported thrombocytopenia, contraindicating intramuscular (IM) vaccination based on Investigator or designee's judgment bleeding disorder, or receipt of anticoagulants in the past 21 days preceding inclusion, contraindicating IM vaccination based on Investigator or designee's judgment unstable acute or chronic illness that in the opinion of the Investigator or designee poses additional risk as a result of participation or that could interfere with the trial procedures receipt of solid-organ or bone marrow transplants in the past 180 days receipt of anti-cancer chemotherapy in the last 90 days moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ≥38.0°C [≥100.4°F]) receipt of any vaccine in the 30 days preceding or on the day of the first trial vaccination or planned receipt of any vaccine in the 30 days following the second trial vaccination except for influenza vaccination, which may be received at any time in relation to trial intervention prior administration of a coronavirus vaccine (SARS-CoV-2, SARS-CoV, Middle East Respiratory Syndrome [MERS-CoV]) participation at the time of trial enrollment (or in the 30 days preceding the first trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure.
Interventions
	Intervention 2 IM doses of 5 mcg, 21 days apart 2 IM doses of 10 mcg, 21 days apart
	Control 2 IM doses of 15 mcg, 21 days apart
Participants
	Randomized 722 participants
	Characteristics of participants Type of participants: Adults N=722 362 males Children: 0 Pregnant women: 0 Immunocompromized patients: 17 Mean age: Age range: 20-92
	Description of participants Adults with and without prior SARS-CoV-2 infection and risk factors for severe disease at 20 centers in the USA and Honduras
Primary outcome
	In the register 1. Presence of immediate adverse events [ Time Frame: Within 30 minutes after vaccination ]; 2. Presence of solicited injection site or systemic reactions [ Time Frame: Within 7 days after vaccination ]; 3. Presence of unsolicited adverse events [ Time Frame: Within 21 days after vaccination ]; 4. Presence of serious adverse events [ Time Frame: From Day 1 to Day 387 ]; 5. Presence of adverse events of special interest [ Time Frame: From Day 1 to Day 387 ]; 6. Presence of medically-attended adverse events [ Time Frame: From Day 1 to Day 387 ]; 7. Neutralizing antibody titer at Day 1 [ Time Frame: Day 1 ]; 8. Neutralizing antibody titer at Day 36 [ Time Frame: Day 36 ]; 9. Neutralizing antibody titer fold-rise post-vaccination [ Time Frame: From Day 1 to Day 36 ]; 10. 2-fold rise and 4-fold-rise in neutralization antibody titer [ Time Frame: From Day 1 to Day 36 ]; 11.Responders, as determined by neutralizing antibody titers at Day 36 [ Time Frame: From Day 1 to Day 36 ]; 12. Neutralizing antibody titer at Day 1 (pre-booster injection) [ Time Frame: Day 1 (pre-booster injection) ]; 13. Neutralizing antibody titer at Day 15 (post-booster injection) [ Time Frame: Day 15 (post-booster injection) ]
	In the report 1) Occurrence of immediate unsolicited systemic AEs occurring within 30 minutes of each injection; 2) solicited injection site reactions (injection site pain, erythema and swelling) and solicited systemic reactions (fever, headache, malaise, myalgia, arthralgia and chills) up to seven days after each injection; 3) unsolicited AEs reported up to 21 days after each injection; 4) MAAEs, serious adverse events (SAEs) and AESIs documented throughout the study. AESIs included anaphylactic reactions, generalized convulsions, thrombocytopenia and potential immune-mediated disorders; 5) Geometric mean titres (GMTs) or geometric mean concentration (GMCs) for NAb and BAb antibodies respectively; 6) the percentage of participants with ≥2-fold or ≥4-fold rise in antibody titres at each post-vaccination time point and the percentage of responders
Documents available	Protocol NR Statistical plan * Data-sharing stated: Yes Data accessibility: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com Corresponding author: Saranya Sridhar, Sanofi Pasteur, Reading, UK, Saranya.Sridhar@sanofi.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 prospective trial registry were used in data extraction and risk of bias assessment. Protocol or statistical analysis plan were not available at the time of data extraction. The primary outcomes in the pre-print article reflect those in the registry. The trial (n = 722) achieved its target sample size (n = 720). The article presented preliminary analyses for a phase 2 trial comparing low-, medium-, and high dose concentrations with ongoing follow-up. A phase 3 trial assessing efficacy using the medium dose started in May 2021 (NCT04904549). This trial was updated on Mars 9th, 2022 afterpublication of study report.