Back to resultsNon-inferiority Trial on Treatments in Early COVID-19
Primary Purpose
COVID-19
Status
Recruiting
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
Sotrovimab
Tixagevimab Cilgavimab
Nirmatrelvir Ritonavir
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 focused on measuring Coronavirus Infections, Monoclonal antibodies, Sotrovimab, Tixagevimab Cilgavimab, Nirmatrelvir Ritonavir
Eligibility Criteria
Inclusion Criteria:
- 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
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 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
- History of convalescent COVID-19 plasma treatment
- Participation, within the last 30 days, in a clinical study involving an investigational intervention
- 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
Sites / Locations
- RCCS Policlinico di S. Orsola
- PO SS Trinità di Cagliari
- Azienda Ospedaliera Cannizzaro
- Azienda Ospedaliera Universitaria Policlinico Vittorio Emanuele
- PO Garibaldi Nesima
- Azienda Socio-Sanitaria Territoriale di CremonaRecruiting
- Ospedale S. Maria AnnunziataRecruiting
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
- Azienda Ospedaliera dei Colli, presidio ospedaliero Cotugno
- Azienda Ospedaliera di PadovaRecruiting
- AOU Policlinico
- Azienda Ospedaliera S. Maria della Misericordia
- Università degli Studi di Pescara
- Fondazione Policlinico Universitario A. Gemelli
- Ospedale San Paolo ASL 2 Savonese
- AOU Città della Salute e Scienza, Presidio Molinette
- Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI)
- Azienda Sanitaria Universitaria Friuli CentraleRecruiting
- Azienda Ospedaliera di VeronaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Experimental
Experimental
Arm Label
Sotrovimab
Tixagevimab Cilgavimab
Nirmatrelvir Ritonavir
Arm Description
Sotrovimab 500 mg administered in 100 mL prefilled 0.9% sodium chloride injection infusion solution over 1/2 hour
300 mg of tixagevimab and 300 mg of cilgavimab administered as two separate consecutive intramuscular injections
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
Outcomes
Primary Outcome Measures
COVID-19 progression
(1) hospitalization or (2) need of supplemental oxygen therapy at home or (3) death within 14 days of randomisation
Secondary Outcome Measures
Visits to the Emergency Room
Number of visits to the Emergency Room without subsequent hospitalization within 28 days of randomization
Duration of supplemental oxygen therapy
Days of supplemental oxygen therapy within 90 days of randomization
Duration of hospitalization
Days of any hospitalization within 90 days of randomization
Non-invasive ventilation
Rate of patients undergoing non-invasive ventilation within 28 days of randomization
Duration of non-invasive ventilation
Days of non-invasive ventilation within 90 days of randomization
Mechanical ventilation
Rate of patients undergoing mechanical ventilation within 28 of randomization
Duration of mechanical ventilation
Days of mechanical ventilation within 90 days of randomization
28-day mortality
Death rate at 28 days of randomization
90-day mortality
Death rate at 90 days of randomization
Duration of symptoms
Days of symptoms within 90 days of randomization
Full Information
NCT ID
NCT05321394
First Posted
April 7, 2022
Last Updated
November 22, 2022
Sponsor
Azienda Ospedaliera Universitaria Integrata Verona
Collaborators
Agenzia Italiana del Farmaco, Azienda Sanitaria-Universitaria Integrata di Udine
1. Study Identification
Unique Protocol Identification Number
NCT05321394
Brief Title
Non-inferiority Trial on Treatments in Early COVID-19
Official Title
Adaptive, Randomized, Non-inferiority Trial on the Use of Monoclonal Antibodies or Antivirals in Outpatients With Mild or Moderate COVID-19
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 7, 2022 (Actual)
Primary Completion Date
September 30, 2023 (Anticipated)
Study Completion Date
December 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Azienda Ospedaliera Universitaria Integrata Verona
Collaborators
Agenzia Italiana del Farmaco, Azienda Sanitaria-Universitaria Integrata di Udine
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
Coronavirus Infections, Monoclonal antibodies, Sotrovimab, Tixagevimab Cilgavimab, Nirmatrelvir Ritonavir
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1095 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Sotrovimab
Arm Type
Active Comparator
Arm Description
Sotrovimab 500 mg administered in 100 mL prefilled 0.9% sodium chloride injection infusion solution over 1/2 hour
Arm Title
Tixagevimab Cilgavimab
Arm Type
Experimental
Arm Description
300 mg of tixagevimab and 300 mg of cilgavimab administered as two separate consecutive intramuscular injections
Arm Title
Nirmatrelvir Ritonavir
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Sotrovimab
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Tixagevimab Cilgavimab
Intervention Description
2 subsequent injections:
tixagevimab 300mg/3mL (100mg/mL)
cilgavimab 300mg/3mL (100mg/mL)
Intervention Type
Drug
Intervention Name(s)
Nirmatrelvir Ritonavir
Intervention Description
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
Primary Outcome Measure Information:
Title
COVID-19 progression
Description
(1) hospitalization or (2) need of supplemental oxygen therapy at home or (3) death within 14 days of randomisation
Time Frame
14 days
Secondary Outcome Measure Information:
Title
Visits to the Emergency Room
Description
Number of visits to the Emergency Room without subsequent hospitalization within 28 days of randomization
Time Frame
28 days
Title
Duration of supplemental oxygen therapy
Description
Days of supplemental oxygen therapy within 90 days of randomization
Time Frame
90 days
Title
Duration of hospitalization
Description
Days of any hospitalization within 90 days of randomization
Time Frame
90 days
Title
Non-invasive ventilation
Description
Rate of patients undergoing non-invasive ventilation within 28 days of randomization
Time Frame
28 days
Title
Duration of non-invasive ventilation
Description
Days of non-invasive ventilation within 90 days of randomization
Time Frame
90 days
Title
Mechanical ventilation
Description
Rate of patients undergoing mechanical ventilation within 28 of randomization
Time Frame
28 days
Title
Duration of mechanical ventilation
Description
Days of mechanical ventilation within 90 days of randomization
Time Frame
90 days
Title
28-day mortality
Description
Death rate at 28 days of randomization
Time Frame
28 days
Title
90-day mortality
Description
Death rate at 90 days of randomization
Time Frame
90 days
Title
Duration of symptoms
Description
Days of symptoms within 90 days of randomization
Time Frame
90 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
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 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
History of convalescent COVID-19 plasma treatment
Participation, within the last 30 days, in a clinical study involving an investigational intervention
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Evelina Tacconelli
Phone
0458128243
Ext
+39
Email
evelina.tacconelli@univr.it
First Name & Middle Initial & Last Name or Official Title & Degree
Fulvia Mazzaferri
Phone
3387310642
Ext
+39
Email
fulvia.mazzaferri@aovr.veneto.it
Facility Information:
Facility Name
RCCS Policlinico di S. Orsola
City
Bologna
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pierluigi Viale
Facility Name
PO SS Trinità di Cagliari
City
Cagliari
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Goffredo Angioni
Facility Name
Azienda Ospedaliera Cannizzaro
City
Catania
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carmelo Iacobello
Facility Name
Azienda Ospedaliera Universitaria Policlinico Vittorio Emanuele
City
Catania
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Arturo Montineri
Facility Name
PO Garibaldi Nesima
City
Catania
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bruno Santi Cacopardo
Facility Name
Azienda Socio-Sanitaria Territoriale di Cremona
City
Cremona
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Angelo Pan
Facility Name
Ospedale S. Maria Annunziata
City
Firenze
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Massimo Antonio Di Pietro
Facility Name
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
City
Milano
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea Gori
Facility Name
Azienda Ospedaliera dei Colli, presidio ospedaliero Cotugno
City
Napoli
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carolina Rescigno
Facility Name
Azienda Ospedaliera di Padova
City
Padova
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Annamaria Cattelan
Facility Name
AOU Policlinico
City
Palermo
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antonio Cascio
Facility Name
Azienda Ospedaliera S. Maria della Misericordia
City
Perugia
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniela Francisci
Facility Name
Università degli Studi di Pescara
City
Pescara
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jacopo Vecchiet
Facility Name
Fondazione Policlinico Universitario A. Gemelli
City
Roma
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Roberto Cauda
Facility Name
Ospedale San Paolo ASL 2 Savonese
City
Savona
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marco Anselmo
Facility Name
AOU Città della Salute e Scienza, Presidio Molinette
City
Torino
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Giuseppe De Rosa
Facility Name
Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI)
City
Trieste
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Roberto Luzzati
Facility Name
Azienda Sanitaria Universitaria Friuli Centrale
City
Udine
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carlo Tascini
Facility Name
Azienda Ospedaliera di Verona
City
Verona
ZIP/Postal Code
37134
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Evelina Tacconelli, MD
Phone
0458128243
Ext
+39
Email
evelina.tacconelli@univr.it
12. IPD Sharing Statement
Learn more about this trial
Non-inferiority Trial on Treatments in Early COVID-19
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