Non-inferiority Trial on Monoclonal Antibodies in COVID-19

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). Differently from casirivimab/imdevimab and sotrovimab, the European Medicines Agency (EMA) has never recommended authorising the combination bamlanivimab/etesevimab for treating COVID-19. Moreover, the evidence on sotrovimab relies on the interim analysis results of an ongoing randomised placebo-controlled clinical trial \[1\], unlike the combinations bamlanivimab/etesevimab and casirivimab/imdevimab, whose results of the randomised placebo-controlled trials were published after having completed the enrolment \[2,3\]. The study aims at assessing the non-inferiority of bamlanivimab plus etesevimab and sotrovimab vs. casirivimab plus imdevimab 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.

Conditions

• COVID-19

Interventions

DRUG

Bamlanivimab Etesevimab

Single intravenous infusion of bamlanivimab 700 mg and etesevimab 1400 mg, administered together \[1 bamlanivimab vial (700 mg/20 mL) and 2 etesevimab vials (700 mg/20 mL)\] in a 250-mL prefilled 0.9% Sodium Chloride infusion bag over one hour.

DRUG

Sotrovimab

Single intravenous infusion of sotrovimab 500 mg (500 mg/8 mL), administered in 100 mL prefilled 0.9% sodium chloride injection infusion solution over 1/2 hour.

DRUG

Casirivimab-Imdevimab

Single intravenous infusion of casirivimab 600 mg + imdevimab 600 mg, administered together in 250 mL prefilled 0.9% sodium chloride injection infusion solution over one hour. Casirivimab and imdevimab are each supplied in individual single use vials. Casirivimab is available as 300 mg/2.5 mL (120 mg/mL) or 1332 mg/11.1 mL (120 mg/mL). Imdevimab is available as 300 mg/2.5 mL (120 mg/mL) or 1332 mg/11.1 mL (120 mg/mL).

Sponsors & Collaborators

• Agenzia Italiana del Farmaco

  collaborator OTHER_GOV

• Azienda Sanitaria-Universitaria Integrata di Udine

  collaborator OTHER

• Azienda Ospedaliera Universitaria Integrata Verona

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

50 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-12-09

Primary Completion

2022-02-05

Completion

2022-04-05

FDA Drug

Yes

Countries

• Italy

Study Locations