NCT05321394

Non-inferiority Trial on Treatments in Early COVID-19

Completed Phase 3 Last updated 7 November 2023

What this trial tests

Phase 3 trial testing Sotrovimab in COVID-19 in 536 participants. Completed in 29 October 2023.

Timeline

7 March 2022

Primary endpoint
29 October 2023

29 October 2023

Quick facts

Lead sponsor	Azienda Ospedaliera Universitaria Integrata Verona
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	536
Start date	7 March 2022
Primary completion	29 October 2023
Estimated completion	29 October 2023
Sites	19 locations across Italy

Drugs / interventions tested

• Sotrovimab — full drug profile →
• Tixagevimab Cilgavimab — full drug profile →
• Nirmatrelvir Ritonavir

Conditions studied

• COVID-19 — all drugs for COVID-19 →

Sponsor

Azienda Ospedaliera Universitaria Integrata Verona — full company profile →

Who can join

50 and older, any sex, with COVID-19. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

The study aims at assessing the non-inferiority of tixagevimab plus cilgavimab and nirmatrelvir plus ritornavir vs. sotrovimab (reference standard due to the wider evidence gathered on its efficacy) on COVID-19 progression in a real-life setting of outpatients 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 sotrovimab at an early-stage of COVID-19, a disease progression of 1% has been estimated in the reference arm. 3% delta margin was considered clinically relevant, taking into account both the estimates of disease progression in the study population in absence of early treatment (7%, based on national data) and the efficacy of the reference standard. Therefore, 1095 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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Oral antiviral treatments for COVID-19: opportunities and challenges.
   Rahmah L, Abarikwu SO, Arero AG, Essouma M, et al · · 2022 · cited 53× · PMID 35871712 · DOI 10.1007/s43440-022-00388-7
2. A Critical Analysis of the Use of Cilgavimab plus Tixagevimab Monoclonal Antibody Cocktail (Evusheld™) for COVID-19 Prophylaxis and Treatment.
   Focosi D, Casadevall A. · · 2022 · cited 52× · PMID 36146805 · DOI 10.3390/v14091999
3. Tixagevimab + Cilgavimab: First Approval.
   Keam SJ. · · 2022 · cited 44× · PMID 35727563 · DOI 10.1007/s40265-022-01731-1
4. Nirmatrelvir combined with ritonavir for preventing and treating COVID-19.
   Reis S, Metzendorf MI, Kuehn R, Popp M, et al · · 2022 · cited 35× · PMID 36126225 · DOI 10.1002/14651858.cd015395.pub2
5. COVID-19 therapeutics.
   Focosi D, Franchini M, Maggi F, Shoham S. · · 2024 · cited 32× · PMID 38771027 · DOI 10.1128/cmr.00119-23
6. Exploratory data on the clinical efficacy of monoclonal antibodies against SARS-CoV-2 Omicron variant of concern.
   Mazzaferri F, Mirandola M, Savoldi A, De Nardo P, et al · · 2022 · cited 20× · PMID 36413383 · DOI 10.7554/elife.79639
7. Nirmatrelvir combined with ritonavir for preventing and treating COVID-19.
   Reis S, Metzendorf MI, Kuehn R, Popp M, et al · · 2023 · cited 16× · PMID 38032024 · DOI 10.1002/14651858.cd015395.pub3
8. Pooled analysis of the MANTICO2 and MONET randomized controlled trials comparing drug efficacy for early treatment of COVID-19 during Omicron waves.
   Mazzotta V, Mazzaferri F, Lanini S, Mirandola M, et al · · 2024 · cited 2× · PMID 39343244 · DOI 10.1016/j.jinf.2024.106294