Non-inferiority Trial on Monoclonal Antibodies in COVID-19

• Status: Recruiting
• Trial end date: 2022-07-01
• Target enrollment: 0
• Participant gender: All

Summary

Currently, 3 anti-SARS-CoV-2 monoclonal antibody products have received Emergency Use Authorizations from the Italian Medicines Agency (AIFA) for the treatment of mild to moderate COVID-19 in non hospitalized patients with laboratory-confirmed SARS-CoV-2 infection who are at high risk for progressing to severe disease and/or hospitalization (bamlanivimab plus etesevimab, sotrovimab, and casirivimab plus imdevimab). The study aims at assessing the non-inferiority of bamlanivimab plus etesevimab and sotrovimab vs. casirivimab plus imdevimab (reference standard due to the wider evidence gathered on its efficacy) on COVID-19 progression in patients aged at least 50 years at an early stage of the disease. The progression of COVID-19 disease (hospitalization, need for supplementary oxygen therapy at home, death) within 14 days of randomisation is the composite outcome variable on which the calculation of the sample size is based. Based on available data regarding the reduction in the number of hospitalisations and medical visits with the use of casirivimab plus imdevimab at an early-stage of COVID-19, a disease progression of 5% has been estimated in the reference arm. 5% delta margin was considered clinically relevant, taking into account both the estimates of disease progression in the study population in absence of early treatment with monoclonal antibodies (20%, based on national data) and the efficacy of the reference standard. Therefore, 1260 participants will be randomly assigned in an equal ratio between the reference standard and each of the other two experimental arms (1:1:1). Randomization will be computer-generated in permuted blocks with a stratification based on site.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Azienda Ospedaliera Universitaria Integrata Verona
• Collaborators: Agenzia Italiana del Farmaco; Azienda Sanitaria-Universitaria Integrata di Udine

Criteria

Inclusion Criteria:

• Age ≥ 50 years

• Informed consent by the subject or legally authorized representative

• Laboratory-confirmed SARS-CoV-2 infection, as determined by antigen or nucleic acid identification in any specimen, within 4 days of eligibility assessment

• Peripheral oxygen saturation ≥ 94% on room air and not requiring supplemental oxygen

• Onset of symptoms within 4 days of eligibility assessment. Onset time of symptoms is defined as the time when the patient experienced the presence of at least one of the following SARS-CoV-2 infection-associated symptoms for the first time (FDA, September 2020):

• Nasal obstruction or congestion

• Cough

• Fever >37.3 °C

• Sore throat

• Body pain or muscle pain

• Headache

• Loss of taste or smell

• Nausea or vomiting

• Diarrhoea

Exclusion Criteria:

• Previously or currently hospitalized or requiring hospitalization

• Respiratory distress with respiratory rate ≥ 25 breaths/min

• Heart rate ≥ 125 beats per minute

• Peripheral oxygen saturation ≤ 93% on room air at sea level

• Known allergies to any of the components used in the formulation of the trial drugs

• Hemodynamic instability requiring use of pressors within 24 hours of randomization

• Suspected or proven serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that could potentially lead to hospitalization within 30 days

• Any co-morbidity requiring surgery within 7 days or that is considered life-threatening within 90 days

• History of positive SARS-CoV-2 serology test

• History of positive SARS-CoV-2 test prior to 4 days of the eligibility assessment

• Previous treatment with a SARS-CoV-2 specific monoclonal antibody

• History of convalescent COVID-19 plasma treatment

• Participation in a clinical study involving an investigational intervention within the last 30 days

• Pregnancy or breast feeding

• Investigator site personnel directly affiliated with this study

• Sexually active women of childbearing potential or sexually active men who are unwilling to practice effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose

• Inability to participate to the study follow-up