Non-inferiority Trial on Treatments in Early COVID-19
Adaptive, Randomized, Non-inferiority Trial on the Use of Monoclonal Antibodies or Antivirals in Outpatients With Mild or Moderate COVID-19
2 other identifiers
interventional
536
1 country
19
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3 covid19
Started Mar 2022
Longer than P75 for phase_3 covid19
19 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 7, 2022
CompletedFirst Submitted
Initial submission to the registry
April 7, 2022
CompletedFirst Posted
Study publicly available on registry
April 11, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 29, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
October 29, 2023
CompletedNovember 7, 2023
November 1, 2023
1.6 years
April 7, 2022
November 5, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
COVID-19 progression
(1) hospitalization or (2) need of supplemental oxygen therapy at home or (3) death within 14 days of randomisation
14 days
Secondary Outcomes (10)
Visits to the Emergency Room
28 days
Duration of supplemental oxygen therapy
90 days
Duration of hospitalization
90 days
Non-invasive ventilation
28 days
Duration of non-invasive ventilation
90 days
- +5 more secondary outcomes
Study Arms (3)
Sotrovimab
ACTIVE COMPARATORSotrovimab 500 mg administered in 100 mL prefilled 0.9% sodium chloride injection infusion solution over 1/2 hour
Tixagevimab Cilgavimab
EXPERIMENTAL300 mg of tixagevimab and 300 mg of cilgavimab administered as two separate consecutive intramuscular injections
Nirmatrelvir Ritonavir
EXPERIMENTAL300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) with all three tablets taken together twice daily for 5 days
Interventions
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.
2 subsequent injections: 1. tixagevimab 300mg/3mL (100mg/mL) 2. cilgavimab 300mg/3mL (100mg/mL)
300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) with all three tablets taken together twice daily for 5 days
Eligibility Criteria
You may qualify if:
- Age ≥ 50 years
- Informed consent by the subject or legally authorized representative
- Laboratory-confirmed SARS-CoV-2 infection, as determined by PCR or other commercial or public health assay in any specimen, no more than 4 days prior to the study drug administration
- Peripheral oxygen saturation ≥ 94% on room air and not requiring supplemental oxygen
- Onset of symptom is no more than 4 days prior to the study drug administration. Onset time of symptom is defined as the time when the patient experienced the presence of at least one of the following (but not limited to) SARS-CoV-2 infection-associated symptom (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
You may not qualify if:
- 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 interventions
- Severe renal impairment (eGFR \<30 mL/min)
- Severe hepatic impairment (Child-Pugh Class C)
- Co-administration with drugs highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions
- Co-administration with potent CYP3A inducers
- 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 in within 30 days
- Any co-morbidity requiring surgery within 7 days or that is considered life-threatening within 90 days
- History of a positive SARS-CoV-2 test prior to the one serving as eligibility for this study
- Other investigational intervention for SARS-CoV-2 prophylaxis within 30 days before dosing
- Previous treatment with a SARS-CoV-2 specific monoclonal antibody
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (19)
RCCS Policlinico di S. Orsola
Bologna, Italy
PO SS Trinità di Cagliari
Cagliari, Italy
Azienda Ospedaliera Cannizzaro
Catania, Italy
Azienda Ospedaliera Universitaria Policlinico Vittorio Emanuele
Catania, Italy
PO Garibaldi Nesima
Catania, Italy
Azienda Socio-Sanitaria Territoriale di Cremona
Cremona, Italy
Ospedale S. Maria Annunziata
Florence, Italy
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, Italy
Azienda Ospedaliera dei Colli, presidio ospedaliero Cotugno
Napoli, Italy
Azienda Ospedaliera di Padova
Padua, Italy
AOU Policlinico
Palermo, Italy
Azienda Ospedaliera S. Maria della Misericordia
Perugia, Italy
Università degli Studi di Pescara
Pescara, Italy
Fondazione Policlinico Universitario A. Gemelli
Roma, Italy
Ospedale San Paolo ASL 2 Savonese
Savona, Italy
AOU Città della Salute e Scienza, Presidio Molinette
Torino, Italy
Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI)
Trieste, Italy
Azienda Sanitaria Universitaria Friuli Centrale
Udine, Italy
Azienda Ospedaliera di Verona
Verona, 37134, Italy
Related Publications (1)
Mazzotta V, Mazzaferri F, Lanini S, Mirandola M, Cozzi Lepri A, Vergori A, Savoldi A, Santoro A, Maccarrone G, Mastrorosa I, Simonetti O, Zottis F, Nicastri E, Rosini G, Rovigo L, Tavernaro L, Sarmati L, Tascini C, Girardi E, Cattelan AM, Antinori A, Tacconelli E; MANTICO2/MONET study group. Pooled analysis of the MANTICO2 and MONET randomized controlled trials comparing drug efficacy for early treatment of COVID-19 during Omicron waves. J Infect. 2024 Nov;89(5):106294. doi: 10.1016/j.jinf.2024.106294. Epub 2024 Sep 27.
PMID: 39343244DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
April 7, 2022
First Posted
April 11, 2022
Study Start
March 7, 2022
Primary Completion
October 29, 2023
Study Completion
October 29, 2023
Last Updated
November 7, 2023
Record last verified: 2023-11