Study to Monitor the Occurrence of Viral Variants in Patients With Compromised Immune Systems Being Treated for COVID-19

Study Overview
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Brief Summary
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Sotrovimab binds to a conserved epitope on the severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 spike protein outside the receptor-binding motif and has been shown to reduce the risk of hospitalization and/or death when administered as early treatment in non-hospitalized patients that are at risk for progression to severe disease. Immunocompromised (IC) patients are prioritized to receive early treatment for COVID-19 as they are at high risk of disease progression, and because of their potential for prolonged viral shedding and the resulting increased risk of emergent viral mutations and potential onward community transmission. This genomic surveillance study will aim to describe changes in the SARS-CoV-2 spike protein observed in IC participants receiving sotrovimab as standard of clinical care in sentinel sites at a national level to assess potential emergence of viral variants.

Official Title
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Prospective Cohort Study to Monitor the Emergence of SARS-CoV-2 Spike Viral Variants in Immunocompromised Non-hospitalized Patients Exposed to Sotrovimab in Great Britain: LUNAR Study

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Sotrovimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be adult and of greater than or equal to (>=) 18 years of age or older at the time of consent Participants must be immunocompromised (IC) population eligible to receive sotrovimab A positive polymerase chain reaction (PCR) or antigen test for SARS-CoV-2 through clinical testing or routine screening undertaken as part of clinical management Prescribed treatment with sotrovimab as standard of clinical care Able to provide informed consent and willing to adhere to study-related procedures Exclusion Criteria: Participants who require hospitalization (related or not to COVID-19) at baseline Participants who initiated sotrovimab therapy in inpatient settings Participants unable to perform nasal/oropharyngeal sample collection Blinded participants from other COVID-19 related trials

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This study is a prospective cohort study which will enroll IC non-hospitalized participants receiving sotrovimab treatment as per standard of clinical care for COVID-19 in sentinel sites.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cohort receiving Sotrovimab<br>Immunocompromised non-hospitalized participants will receive sotrovimab as standard of clinical care for COVID-19 in sentinel sites | Drug: Sotrovimab<br>* Sotrovimab dose and administration per standard of clinical care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants eligible for sequence analysis with amino acids (AA) change from baseline in the epitope of sotrovimab binding |  | Baseline (Day 0) and up to Day 28 ([plus-minus] ± 2 days) | 
| Proportion of participants eligible for sequence analysis that have any AA, change from baseline in the spike protein |  | Baseline (Day 0) and up to Day 28 (± 2 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants eligible for sequence analysis with variants of concern (VOC) and variants under investigation (VUI) on the earliest possible sample including baseline |  | Baseline (Day 0) and up to Day 28 (± 2 days) | 
| Proportion of participants with undetectable virus by reverse transcriptase polymerase chain reaction (RT-PCR) |  | Baseline (Day 0) and up to Day 28 (± 2 days) | 
| Proportion of participants with all cause hospital admissions and COVID-19 related hospital admissions |  | Up to Day 28 (± 2 days) | 
| Proportion of participants on new or increased oxygen support, including those requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO) |  | Up to Day 28 (± 2 days) | 
| Proportion of participants with all cause intensive care unit (ICU) admission |  | Up to Day 28 (± 2 days) | 
| Proportion of participants with all cause deaths and COVID-19 related deaths |  | Up to Day 28 (± 2 days) | 
| Number of participants with AA changes in SARS-CoV-2 spike protein is >5% in samples compared to baseline following sotrovimab administration | For samples with viral load above the threshold for allelic frequency determination, AA changes in SARS-CoV-2 spike protein at greater than (>) 5 percentage (%) allelic frequency compared to baseline will be reported | Baseline (Day 0) and up to Day 28 (± 2 days) | 
| Number of participants with AA changes in the consensus sequence (>50%) of SARS-CoV-2 spike protein samples from baseline following sotrovimab administration | For samples with viral load below the threshold for low (5%) allelic frequency analysis, but above the threshold for consensus sequence generation, AA changes in the SARS-CoV-2 spike protein consensus sequence (> 50%) from baseline will be reported | Baseline (Day 0) and up to Day 28 (± 2 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS CoV-2, LUNAR, Coronavirus disease 2019 (COVID-19), Pandemic, Sotrovimab, Monoclonal antibody, Immunocompromised (IC)