Covid19Phase 3NCT04913675
Intramuscular and Intravenous VIR-7831 (Sotrovimab) for Mild/Moderate COVID-19.
A Phase 3 study testing sotrovimab in people with Covid19, run by Vir Biotechnology, Inc. at 50 sites in 3 countries.
Trial summary
The COMET-TAIL main study evaluated efficacy, safety, and tolerability of IM sotrovimab versus IV sotrovimab in high-risk patients for the treatment of mild/moderate COVID-19. In the safety substudy, the aim was to evaluate the safety and tolerability of sotrovimab across a single ascending dose level and over… Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Covid19
- What is being tested?
- sotrovimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,065 participants
- Where
- 50 sitesin 3 countries
- Study dates
- 10 Jun 2021to 24 Mar 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Main Study participant must be aged 12 years or older AND at high risk of progression of COVID-19 or > 55 years old
- Sub-Study participants must be aged 18 years or older at time of consent AND at high risk of progression of COVID-19 or ≥ 55 years old
- Participants must have a positive SARS-CoV-2 test result and oxygen saturation ≥94% on room air and have COVID-19 symptoms and be less than or equal to 7 days from onset of symptoms
Who cannot join
- Currently hospitalized or judged by the investigator as likely to require hospitalization in the next 24 hours
- Symptoms consistent with severe COVID-19
- Participants who, in the judgement of the investigator are likely to die in the next 7 days
- Known hypersensitivity to any constituent present in the investigational product
Trial locations and contacts
50 sites in 3 countries.
50 sites in 3 countries
United States48 sites
Investigative Site
Anniston, Alabama, 36207
Investigative Site
Atlanta, Georgia, 30318
Investigative Site
Baytown, Texas, 77521
Investigative Site
Bradenton, Florida, 34208
Investigative Site
Columbus, Ohio, 43215
Investigative Site
Doral, Florida, 33126
Investigative Site
Doral, Florida, 33166
Investigative Site
Forney, Texas, 75126
Investigative Site
Gainesville, Florida, 32607
Investigative Site
Hialeah, Florida, 33012
Investigative Site
Hialeah, Florida, 33013
Investigative Site
Hialeah, Florida, 33016
Investigative Site
High Point, North Carolina, 27262
Investigative Site
Houston, Texas, 77017
Investigative Site
Houston, Texas, 77024
Investigative Site
Houston, Texas, 77090
Investigative Site
Idaho Falls, Idaho, 83404
Investigative Site
Kirkland, Washington, 98034
Investigative Site
Laredo, Texas, 78041
Investigative Site
Las Vegas, Nevada, 89113
Investigative Site
Los Angeles, California, 90017
Investigative Site
Mesa, Arizona, 85210
Investigative Site
Mesquite, Texas, 75149
Investigative Site
Miami, Florida, 33032
Investigative Site
Miami, Florida, 33125
Investigative Site
Miami, Florida, 33126
Investigative Site
Miami, Florida, 33135
Investigative Site
Miami, Florida, 33144
Investigative Site
Miami, Florida, 33155
Investigative Site
Miami, Florida, 33175
Investigative Site
Miami, Florida, 33176
Investigative Site
Miami, Florida, 33180
Investigative Site
Mishawaka, Indiana, 46544
Investigative Site
Mount Airy, North Carolina, 27030
Investigative Site
North Miami Beach, Florida, 33169
Investigative Site
Ormond Beach, Florida, 32174
Investigative Site
Palmetto Bay, Florida, 33157
Investigative Sites
Pembroke Pines, Florida, 33024
Investigative Site
Pharr, Texas, 78577
Investigative Site
Pompano Beach, Florida, 33064
Investigative Site
Rolling Hills Estates, California, 90274
Investigative Site
Seattle, Washington, 98109
Investigative Site
Smithfield, Pennsylvania, 15478
Investigative Site
Sterling Heights, Michigan, 48126
Investigative Site
Tampa, Florida, 33614
Investigative Site
Tampa, Florida, 33615
Investigative Site
The Bronx, New York, 10456
Investigative Site
Tucson, Arizona, 85712
About this study
Official title: A Phase 3 Randomized, Multi-center, Open Label Study to Assess the Efficacy, Safety, and Tolerability of Monoclonal Antibody VIR-7831 (Sotrovimab) Given Intramuscularly Versus Intravenously for the Treatment of Mild/Moderate Coronavirus Disease 2019 (COVID-19) in High-risk Non-hospitalized Patients; Safety Substudy Assessing the Safety and Tolerability of Single Ascending Dose Monoclonal Antibody VIR-7831
The COMET-TAIL main study evaluated efficacy, safety, and tolerability of IM sotrovimab versus IV sotrovimab in high-risk patients for the treatment of mild/moderate COVID-19. In the safety substudy, the aim was to evaluate the safety and tolerability of sotrovimab across a single ascending dose level and over different infusion times when given for the treatment of mild/moderate COVID-19 to participants at high risk of disease progression
Main study was completed successfully. The safety sub-study was discontinued early in the context of evolving variants with increased fold changes in the in vitro half maximal inhibitory concentration (IC50) and uncertainty in the clinical relevance of these changes.
- Conditions
- Covid19
- Being tested
- sotrovimab
- Keywords
- SARS-CoV-2, coronavirus disease 2019, COVID-19, early treatment, coronavirus
- Medical subject headings
- COVID-19, Coronavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sotrovimabBiological
Sotrovimab 500 mg given by intravenous infusion over 15 min
sotrovimabBiological
Sotrovimab 500 mg given by intramuscular injection
sotrovimabBiological
Sotrovimab 250 mg given by intramuscular injection
sotrovimabBiological
Sotrovimab 2000 mg given by intravenous infusion over 60 min
SotrovimabBiological
Sotrovimab 2000 mg given by intravenous infusion over 30 min
SotrovimabBiological
Sotrovimab 2000 mg given by intravenous infusion over 15 min
SotrovimabBiological
Sotrovimab up to 3000 mg given by intravenous infusion over 90 min
| Study group | Role | What they receive |
|---|---|---|
| Main Study - Sotrovimab 500 mg IV | Active comparator | Not described Receives: Biological: sotrovimab |
| Main Study - Sotrovimab 500 mg IM | Experimental | Not described Receives: Biological: sotrovimab |
| Main Study - Sotrovimab 250 mg IM | Experimental | Not described Receives: Biological: sotrovimab |
| Substudy (Cohort A) - Sotrovimab 2000 mg IV | Experimental | Not described Receives: Biological: sotrovimab |
| Substudy (Optional Cohort B1) - Sotrovimab 2000 mg IV | Experimental | Not described Receives: Biological: Sotrovimab |
| Substudy (Optional Cohort B2) - Sotrovimab 2000 mg IV | Experimental | Not described Receives: Biological: Sotrovimab |
| Substudy (Optional Cohort C) - Sotrovimab up to 3000 mg IV | Experimental | Not described Receives: Biological: Sotrovimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Main Study: Percentage of Participants Who Had Progression of Coronavirus Disease 2019 (COVID-19) Through Day 29 by Hospitalization >24 Hours or Death Due to Any Cause (Weekly and Daily Imputation)
Progression of COVID-19 through Day 29 as defined by hospitalization >24 hours for acute management of illness due to any cause or death. Percentage values are rounded off.
Measured: Up to Day 29
Safety Sub-study: Number of Participants With Non-Serious Adverse Events (Non-SAE) and Serious Adverse Events (SAEs) Through Day 8
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or any other situation according to medical or scientific judgement. Adverse events which were not Serious were considered as Non-Serious adverse events.
Measured: Up to Day 8
Safety Sub-study: Number of Participants With Infusion-related Reaction Including Hypersensitivity Through Day 8
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Adverse events of special interest (AESI) included infusion-related reaction including hypersensitivity. Data for number of participants with infusion-related reaction including hypersensitivity has been presented.
Measured: Up to Day 8
Safety Sub-study: Number of Participants With Any Disease Related Events Through Day 8
AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, were reported as a disease related events.
Measured: Up to Day 8
Secondary outcomes (31)
Main Study: Number of Participants With Common Non-Serious Adverse Events (Non-SAEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Data for Common (>=1%) non-SAEs are presented.
Measured: Up to Week 12
Main Study: Number of Participants With Serious Adverse Events (SAEs)
An SAE is defined as any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, significant medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed before.
Measured: Up to Week 36
Main Study: Number of Participants With Any Infusion- or Injection-related Reaction Including Hypersensitivity
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESI included infusion- or injection-related reaction including hypersensitivity. Data for number of participants with any infusion- or injection-related reaction including hypersensitivity has been presented.
Measured: Up to Week 36
Main Study: Number of Participants With Any Local Site Reaction by Maximum Severity After IM Administration
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESIs included any solicited local site reactions. AESI were graded according to the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials 2007, Food and Drug Administration, where Grade 1=Mild toxicity; Grade 2=Moderate toxicity; Grade 3=Severe toxicity; and Grade 4= Potentially life-threatening toxicity. Higher Grade indicates higher severity. Data for any worst case post-Baseline has been presented.
Measured: Up to Week 36
Main Study: Number of Participants With Any Disease Related Events
AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, were reported as a disease related events.
Measured: Up to Week 36
Safety Sub-study: Number of Participants With Non-SAEs Through Week 12
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Adverse events which were no serious, were considered as non-SAEs.
Measured: Up to Week 12
Safety Sub-study: Number of Participants With SAEs Through Week 36
An SAE is defined as any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or any other situation according to medical or scientific judgement.
Measured: Up to Week 36
Safety Sub-study: Number of Participants With Any Infusion-related Reaction Including Hypersensitivity Through Week 12
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESI is infusion-related reaction including hypersensitivity.
Measured: Up to Week 12
Safety Sub-study: Number of Participants With Any Disease Related Events Through Week 12
AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, were reported as a disease related events.
Measured: Up to Week 12
Main Study: Number of Participants With Treatment-emergent Positive Anti-drug Antibody
Serum samples were collected for the determination of anti-drug antibodies (ADA) using a validated electrochemiluminescent (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'positive'. Confirmed positive ADA samples were further characterized in the titration assay to quasi-quantitate the amount of ADA in the sample.
Measured: Up to Week 24
Main Study: Titers of Anti-drug Antibodies Against Sotrovimab
Confirmed positive ADA samples were further analyzed to obtain the titer of the antibodies. Titer is defined as the reciprocal of the highest dilution that yield results at or above the plate-based titer cut point x MRD. Titer Median and range from treatment emergent and unaffected are described below. Immunogenicity results were categorized as treatment- induced, treatment-boosted, and treatment-unaffected. Treatment-induced=those who are ADA negative or missing data at baseline and who have at least one post-dose ADA positive sample; Treatment boosted=those who are ADA positive at baseline and have a >4*Baseline titer; Treatment unaffected=those who are positive at baseline and post-Baseline titer <=4*Baseline titer or all post- Baseline negative. Treatment emergent = treatment induced or treatment boosted
Measured: Up to Week 24
Safety Sub-study: Number of Participants With Treatment-emergent Positive Anti-drug Antibody Through Week 24
Serum samples were collected for the determination of anti-drug antibodies (ADA) using a validated electrochemiluminescent (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'positive'. Confirmed positive ADA samples were further characterized in the titration assay to quasi-quantitate the amount of ADA in the sample.
Measured: Up to Week 24
Safety Sub-study: Titers of Anti-drug Antibodies Against Sotrovimab Through Week 24
Confirmed positive ADA samples were further analyzed to obtain the titer of the antibodies. Titer is defined as the reciprocal of the highest dilution that yield results at or above the plate-based titer cut point x MRD. Titer Median and range from treatment emergent and unaffected are described below. Immunogenicity results were categorized as treatment- induced, treatment-boosted, and treatment-unaffected. Treatment-induced=those who are ADA negative or missing data at baseline and who have at least one post-dose ADA positive sample; Treatment boosted=those who are ADA positive at baseline and have a >4*Baseline titer; Treatment unaffected=those who are positive at baseline and post-Baseline titer <=4*Baseline titer or all post- Baseline negative. Treatment emergent = treatment induced or treatment boosted
Measured: Up to Week 24
Safety Sub-study: Number of Participants With Positive Neutralizing Antibodies
Blood samples were collected for the determination of positive neutralizing antibodies. A neutralizing antibody assay was performed. Neutralizing antibody test was only carried out for participants who have had a positive confirmatory binding antibody test result at visit. A participant was considered positive if they had at least one positive post-Baseline neutralizing antibody result.
Measured: Up to Week 24
Main Study: Percentage of Participants Who Had Progression of COVID-19 Through Day 29 by Emergency Room Visit or Hospitalization or Death (Weekly Imputation)
Progression of COVID-19 through Day 29 as defined by visit to a hospital emergency room for management of illness or hospitalization for acute management of illness for any duration and for any cause or death. Percentage values are rounded off.
Measured: Up to Day 29
Main Study: Percentage of Participants Who Progress to Develop Severe and/or Critical Respiratory COVID-19 by Visit
Participants were defined as progressing to develop severe respiratory COVID-19 if they required supplemental oxygen either by nasal cannula, face mask, high-flow oxygen devices, or non-invasive ventilation. Participants were defined as progressing to develop critical respiratory COVID-19 if they required invasive mechanical ventilation or extracorporeal membrane oxygenation. Percentage values are rounded off.
Measured: Day 8, Day 15, Day 22, and Day 29
Main Study: Mean Area Under the Curve (AUC) of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Viral Load From Day 1 to Day 8
AUC of SARS-CoV-2 viral load was measured by Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) from Day 1 to Day 8 in nasopharyngeal swab samples.
Measured: Day 1 to Day 8
Main Study: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 8 After Administration of Sotrovimab 500 mg IV and IM
AUC of SARS-CoV-2 viral load was measured by qRT-PCR from Day 1 to Day 8 in nasopharyngeal swab samples. Least squares geometric mean and 90 percent (%) confidence interval has been presented.
Measured: Day 1 to Day 8
Main Study: Change From Baseline in Viral Load as Measured by qRT-PCR at Day 8
Viral load was based on nasopharyngeal swab samples and was measured by qRT-PCR. Baseline was defined as the latest non-missing value prior to dosing (or latest value on or prior to nominal Day 1 for participants that were not dosed). Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Measured: Baseline (Day 1) and at Day 8
Main Study: Percentage of Participants With Persistently High SARS-CoV-2 Viral Load at Day 8
Percentage of participants with a persistently high viral load were categorized as >=4.1 log10 copies/mL and <4.1 log10 copies/mL. Percentage of participants with a persistently high SARS-CoV-2 viral load at Day 8 was assessed via qRT-PCR in nasopharyngeal swab samples. Percentage values are rounded off.
Measured: At Day 8
Main Study: Serum Concentration of Sotrovimab After Intravenous Administration
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab.
Measured: Day 1: Pre-dose, Day 8, Day 15, Day 29, Week 12, Week 20 and Week 24
Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration
Blood samples were collected at indicated time points for PK analysis of Sotrovimab.
Measured: Day 1: Pre-dose, Day 8, Day 15, Day 29, Week 12, Week 20 and Week 24
Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab.
Measured: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Safety Sub-study: Area Under the Serum Concentration-time Curve From Days 1 to 29 of After Intravenous Administration (AUCD1-29) of Sotrovimab
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method.
Measured: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose
Safety Sub-study: Maximum Serum Concentration of Sotrovimab After Intravenous Administration (Cmax)
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method.
Measured: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Safety Sub-study: Apparent Volume of Distribution at Steady State of Sotrovimab After Intravenous Administration (Vss)
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method.
Measured: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Safety Sub-study: Area Under the Serum Concentration-Time Curve Extrapolated From Zero to Infinity of Sotrovimab After Intravenous Administration (AUC[0-inf])
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method.
Measured: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Safety Sub-study: Terminal Elimination Half-life of Sotrovimab After Intravenous Administration (t1/2)
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method.
Measured: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Safety Sub-study: Apparent Volume of Distribution During the Elimination Phase of Sotrovimab After Intravenous Administration (Vz)
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method.
Measured: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Safety Sub-study: Clearance of Sotrovimab After Intravenous Administration (CL)
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method.
Measured: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Safety Sub-study: Time to Reach Maximum Serum Concentration of Sotrovimab After Intravenous Administration (Tmax)
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method.
Measured: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2021
- Study start10 Jun 2021
- Primary completion19 Jul 2022
- Study completion24 Mar 2023
Why it stopped: The safety sub-study was discontinued early in the context of evolving variants with increased fold changes in the in vitro half maximal inhibitory concentration (IC50) and uncertainty in the clinical relevance of these changes
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,065 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vir Biotechnology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04913675
- Sponsor's protocol ID
- VIR-7831-5008
- Status last verified
- Jan 2024
- First submitted
- 27 May 2021
- Last updated
- 7 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Shapiro AE, Sarkis E, Acloque J, Free A, Gonzalez-Rojas Y, Hussain R, Juarez E, Moya J, Parikh N, Inman D, Cebrik D, Nader A, Noormohamed N, Wang Q, Skingsley A, Austin D, Peppercorn A, Agostini ML, Parra S, Chow S, Mogalian E, Pang PS, Hong DK, Sager JE, Yeh WW, Alexander EL, Gaffney LA, Kohli A. Intramuscular vs Intravenous SARS-CoV-2 Neutralizing Antibody Sotrovimab for Treatment of COVID-19 (COMET-TAIL): A Randomized Noninferiority Clinical Trial. Open Forum Infect Dis. 2023 Jul 14;10(8):ofad354. doi: 10.1093/ofid/ofad354. eCollection 2023 Aug.
PubMed 37577112Moya J, Temech M, Parra S, Juarez E, Hernandez-Loy R, Gutierrez JCM, Diaz J, Hussain R, Segal S, Xu C, Skingsley A, Schnell G, El-Zailik A, Sager JE, Aldinger M, Alexander EL, Acloque G. Safety, Virology, Pharmacokinetics, and Clinical Experience of High-Dose Intravenous Sotrovimab for the Treatment of Mild to Moderate COVID-19: An Open-Label Clinical Trial. Open Forum Infect Dis. 2023 Jul 10;10(7):ofad344. doi: 10.1093/ofid/ofad344. eCollection 2023 Jul.
PubMed 37520411Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
PubMed 34473343
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Randomized, Multi-center, Open Label Study to Assess the Efficacy, Safety, and Tolerability of Monoclonal Antibody VIR-7831 (Sotrovimab) Given Intramuscularly Versus Intravenously for the Treatment of Mild/Moderate Coronavirus Disease 2019 (COVID-19) in High-risk Non-hospitalized Patients; Safety Substudy Assessing the Safety and Tolerability of Single Ascending Dose Monoclonal Antibody VIR-7831
- ClinicalTrials.gov ID
- NCT04913675
- Acronym / sponsor ID
- VIR-7831-5008
- Conditions
- Covid19
- Keywords
- SARS-CoV-2, coronavirus disease 2019, COVID-19, early treatment, coronavirus
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The safety sub-study was discontinued early in the context of evolving variants with increased fold changes in the in vitro half maximal inhibitory concentration (IC50) and uncertainty in the clinical relevance of these changes
- Enrolment
- 1,065 participants (actual)
- Lead sponsor
- Vir Biotechnology, Inc.Industry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Study start
- 10 Jun 2021 (actual)
- Primary completion
- 19 Jul 2022 (actual)
- Study completion
- 24 Mar 2023 (actual)
- First posted
- 4 Jun 2021 (actual)
- Results
- Posted 26 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The COMET-TAIL main study evaluated efficacy, safety, and tolerability of IM sotrovimab versus IV sotrovimab in high-risk patients for the treatment of mild/moderate COVID-19. In the safety substudy, the aim was to evaluate the safety and tolerability of sotrovimab across a single ascending dose level and over different infusion times when given for the treatment of mild/moderate COVID-19 to participants at high risk of disease progression
Main study was completed successfully. The safety sub-study was discontinued early in the context of evolving variants with increased fold changes in the in vitro half maximal inhibitory concentration (IC50) and uncertainty in the clinical relevance of these changes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Main Study - Sotrovimab 500 mg IV | Active comparator | Biological: sotrovimab |
| Main Study - Sotrovimab 500 mg IM | Experimental | Biological: sotrovimab |
| Main Study - Sotrovimab 250 mg IM | Experimental | Biological: sotrovimab |
| Substudy (Cohort A) - Sotrovimab 2000 mg IV | Experimental | Biological: sotrovimab |
| Substudy (Optional Cohort B1) - Sotrovimab 2000 mg IV | Experimental | Biological: Sotrovimab |
| Substudy (Optional Cohort B2) - Sotrovimab 2000 mg IV | Experimental | Biological: Sotrovimab |
| Substudy (Optional Cohort C) - Sotrovimab up to 3000 mg IV | Experimental | Biological: Sotrovimab |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Main Study participant must be aged 12 years or older AND at high risk of progression of COVID-19 or > 55 years old
- Sub-Study participants must be aged 18 years or older at time of consent AND at high risk of progression of COVID-19 or ≥ 55 years old
- Participants must have a positive SARS-CoV-2 test result and oxygen saturation ≥94% on room air and have COVID-19 symptoms and be less than or equal to 7 days from onset of symptoms
Key exclusion criteria (4 listed)
- Currently hospitalized or judged by the investigator as likely to require hospitalization in the next 24 hours
- Symptoms consistent with severe COVID-19
- Participants who, in the judgement of the investigator are likely to die in the next 7 days
- Known hypersensitivity to any constituent present in the investigational product
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sotrovimabSotrovimab 500 mg given by intravenous infusion over 15 min | Biological | Main Study - Sotrovimab 500 mg IV |
| sotrovimabSotrovimab 500 mg given by intramuscular injection | Biological | Main Study - Sotrovimab 500 mg IM |
| sotrovimabSotrovimab 250 mg given by intramuscular injection | Biological | Main Study - Sotrovimab 250 mg IM |
| sotrovimabSotrovimab 2000 mg given by intravenous infusion over 60 min | Biological | Substudy (Cohort A) - Sotrovimab 2000 mg IV |
| SotrovimabSotrovimab 2000 mg given by intravenous infusion over 30 min | Biological | Substudy (Optional Cohort B1) - Sotrovimab 2000 mg IV |
| SotrovimabSotrovimab 2000 mg given by intravenous infusion over 15 min | Biological | Substudy (Optional Cohort B2) - Sotrovimab 2000 mg IV |
| SotrovimabSotrovimab up to 3000 mg given by intravenous infusion over 90 min | Biological | Substudy (Optional Cohort C) - Sotrovimab up to 3000 mg IV |
Primary outcome
Main Study: Percentage of Participants Who Had Progression of Coronavirus Disease 2019 (COVID-19) Through Day 29 by Hospitalization >24 Hours or Death Due to Any Cause (Weekly and Daily Imputation)
Time frame: Up to Day 29
Progression of COVID-19 through Day 29 as defined by hospitalization >24 hours for acute management of illness due to any cause or death. Percentage values are rounded off.
Safety Sub-study: Number of Participants With Non-Serious Adverse Events (Non-SAE) and Serious Adverse Events (SAEs) Through Day 8
Time frame: Up to Day 8
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or any other situation according to medical or scientific judgement. Adverse events which were not Serious were considered as Non-Serious adverse events.
Safety Sub-study: Number of Participants With Infusion-related Reaction Including Hypersensitivity Through Day 8
Time frame: Up to Day 8
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Adverse events of special interest (AESI) included infusion-related reaction including hypersensitivity. Data for number of participants with infusion-related reaction including hypersensitivity has been presented.
Safety Sub-study: Number of Participants With Any Disease Related Events Through Day 8
Time frame: Up to Day 8
AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, were reported as a disease related events.
31 secondary outcomes
Main Study: Number of Participants With Common Non-Serious Adverse Events (Non-SAEs)
Time frame: Up to Week 12
Main Study: Number of Participants With Serious Adverse Events (SAEs)
Time frame: Up to Week 36
Main Study: Number of Participants With Any Infusion- or Injection-related Reaction Including Hypersensitivity
Time frame: Up to Week 36
Main Study: Number of Participants With Any Local Site Reaction by Maximum Severity After IM Administration
Time frame: Up to Week 36
Main Study: Number of Participants With Any Disease Related Events
Time frame: Up to Week 36
Safety Sub-study: Number of Participants With Non-SAEs Through Week 12
Time frame: Up to Week 12
Safety Sub-study: Number of Participants With SAEs Through Week 36
Time frame: Up to Week 36
Safety Sub-study: Number of Participants With Any Infusion-related Reaction Including Hypersensitivity Through Week 12
Time frame: Up to Week 12
Safety Sub-study: Number of Participants With Any Disease Related Events Through Week 12
Time frame: Up to Week 12
Main Study: Number of Participants With Treatment-emergent Positive Anti-drug Antibody
Time frame: Up to Week 24
Main Study: Titers of Anti-drug Antibodies Against Sotrovimab
Time frame: Up to Week 24
Safety Sub-study: Number of Participants With Treatment-emergent Positive Anti-drug Antibody Through Week 24
Time frame: Up to Week 24
Safety Sub-study: Titers of Anti-drug Antibodies Against Sotrovimab Through Week 24
Time frame: Up to Week 24
Safety Sub-study: Number of Participants With Positive Neutralizing Antibodies
Time frame: Up to Week 24
Main Study: Percentage of Participants Who Had Progression of COVID-19 Through Day 29 by Emergency Room Visit or Hospitalization or Death (Weekly Imputation)
Time frame: Up to Day 29
Main Study: Percentage of Participants Who Progress to Develop Severe and/or Critical Respiratory COVID-19 by Visit
Time frame: Day 8, Day 15, Day 22, and Day 29
Main Study: Mean Area Under the Curve (AUC) of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Viral Load From Day 1 to Day 8
Time frame: Day 1 to Day 8
Main Study: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 8 After Administration of Sotrovimab 500 mg IV and IM
Time frame: Day 1 to Day 8
Main Study: Change From Baseline in Viral Load as Measured by qRT-PCR at Day 8
Time frame: Baseline (Day 1) and at Day 8
Main Study: Percentage of Participants With Persistently High SARS-CoV-2 Viral Load at Day 8
Time frame: At Day 8
Main Study: Serum Concentration of Sotrovimab After Intravenous Administration
Time frame: Day 1: Pre-dose, Day 8, Day 15, Day 29, Week 12, Week 20 and Week 24
Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration
Time frame: Day 1: Pre-dose, Day 8, Day 15, Day 29, Week 12, Week 20 and Week 24
Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration
Time frame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Safety Sub-study: Area Under the Serum Concentration-time Curve From Days 1 to 29 of After Intravenous Administration (AUCD1-29) of Sotrovimab
Time frame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose
Safety Sub-study: Maximum Serum Concentration of Sotrovimab After Intravenous Administration (Cmax)
Time frame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Safety Sub-study: Apparent Volume of Distribution at Steady State of Sotrovimab After Intravenous Administration (Vss)
Time frame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Safety Sub-study: Area Under the Serum Concentration-Time Curve Extrapolated From Zero to Infinity of Sotrovimab After Intravenous Administration (AUC[0-inf])
Time frame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Safety Sub-study: Terminal Elimination Half-life of Sotrovimab After Intravenous Administration (t1/2)
Time frame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Safety Sub-study: Apparent Volume of Distribution During the Elimination Phase of Sotrovimab After Intravenous Administration (Vz)
Time frame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Safety Sub-study: Clearance of Sotrovimab After Intravenous Administration (CL)
Time frame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Safety Sub-study: Time to Reach Maximum Serum Concentration of Sotrovimab After Intravenous Administration (Tmax)
Time frame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37577112Shapiro AE, Sarkis E, Acloque J, Free A, Gonzalez-Rojas Y, Hussain R, Juarez E, Moya J, Parikh N, Inman D, Cebrik D, Nader A, Noormohamed N, Wang Q, Skingsley A, Austin D, Peppercorn A, Agostini ML, Parra S, Chow S, Mogalian E, Pang PS, Hong DK, Sager JE, Yeh WW, Alexander EL, Gaffney LA, Kohli A. Intramuscular vs Intravenous SARS-CoV-2 Neutralizing Antibody Sotrovimab for Treatment of COVID-19 (COMET-TAIL): A Randomized Noninferiority Clinical Trial. Open Forum Infect Dis. 2023 Jul 14;10(8):ofad354. doi: 10.1093/ofid/ofad354. eCollection 2023 Aug.
- Derived from this study: PubMed 37520411Moya J, Temech M, Parra S, Juarez E, Hernandez-Loy R, Gutierrez JCM, Diaz J, Hussain R, Segal S, Xu C, Skingsley A, Schnell G, El-Zailik A, Sager JE, Aldinger M, Alexander EL, Acloque G. Safety, Virology, Pharmacokinetics, and Clinical Experience of High-Dose Intravenous Sotrovimab for the Treatment of Mild to Moderate COVID-19: An Open-Label Clinical Trial. Open Forum Infect Dis. 2023 Jul 10;10(7):ofad344. doi: 10.1093/ofid/ofad344. eCollection 2023 Jul.
- Derived from this study: PubMed 34473343Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
50 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing sotrovimab in people with Covid19, run by Vir Biotechnology, Inc. at 50 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 50 sites in United States, France, Ukraine. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Main Study: Percentage of Participants Who Had Progression of Coronavirus Disease 2019 (COVID-19) Through Day 29 by Hospitalization >24 Hours or Death Due to Any Cause (Weekly and Daily Imputation) (time frame: Up to Day 29). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04913675, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2024.