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

Phase 4

Completed

Conditions: COVID-19

Interventions: Drug: Sotrovimab

Registration Number: NCT05305651

Lead Sponsor: GlaxoSmithKline

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 217

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Participants receiving Sotrovimab	Sotrovimab	Immunocompromised non-hospitalized participants will receive sotrovimab as standard of clinical care for COVID-19 in sentinel sites

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Emergent Amino Acid Substitutions Greater Than (>) 5 Percent (%) and >50% Allelic Frequency in the Sotrovimab Epitope at Day 7	At Day 7	SARS-CoV-2 spike analysis was carried out by nucleotide sequencing of the SARS-CoV-2 spike protein by Next generation sequencing (NGS) analysis of participant nasal/oropharyngeal swab samples. The nucleotide sequences were translated, and the amino acid (AA) sequences aligned and compared to a reference sequence. Treatment emergent (TE) substitutions are defined as AA differences in a post-Baseline sample that were not present at Baseline at the defined threshold for minority and consensus analysis. The epitope is part of the spike protein, and it was analyzed separately from the rest of spike. The number of participants with TE substitutions in the sotrovimab epitope reflects participants that had a TE change in the spike protein at the sotrovimab epitope position only. AA substitutions compared to the reference strain are presented at Day 7.
Number of Participants With Treatment Emergent Amino Acid Substitutions >5% and >50% Allelic Frequency in the Sotrovimab Epitope at Day 14	At Day 14	SARS-CoV-2 spike analysis was carried out by nucleotide sequencing of the SARS-CoV-2 spike protein by NGS analysis of participant nasal/oropharyngeal swab samples. The nucleotide sequences were translated, and AA sequences aligned and compared to a reference sequence. Treatment emergent (TE) substitutions are defined as AA differences in a post-Baseline sample that were not present at Baseline at the defined threshold for minority and consensus analysis. The epitope is part of the spike protein, and it was analyzed separately from the rest of spike. The number of participants with TE substitutions in the sotrovimab epitope reflects participants that had a TE change in the spike protein at the sotrovimab epitope position only. AA substitutions compared to the reference strain are presented at Day 14.
Number of Participants With Treatment Emergent Amino Acid Substitutions >5% and >50% Allelic Frequency in the Sotrovimab Epitope at Day 28	At Day 28	SARS-CoV-2 spike analysis was carried out by nucleotide sequencing of the SARS-CoV-2 spike protein by NGS analysis of participant nasal/oropharyngeal swab samples. The nucleotide sequences were translated, and AA sequences aligned and compared to a reference sequence. Treatment emergent (TE) substitutions are defined as AA differences in a post-Baseline sample that were not present at Baseline at the defined threshold for minority and consensus analysis. The epitope is part of the spike protein, and it was analyzed separately from the rest of spike. The number of participants with TE substitutions in the sotrovimab epitope reflects participants that had a TE change in the spike protein at the sotrovimab epitope position only. AA substitutions compared to the reference strain are presented at Day 28.
Number of Participants With Treatment Emergent Amino Acid Substitutions >5% and >50% Allelic Frequency in the Spike Protein at Day 7	At Day 7	SARS-CoV-2 spike analysis was carried out by nucleotide sequencing of the SARS-CoV-2 spike protein by NGS analysis of participant nasal/oropharyngeal swab samples. The nucleotide sequences were translated, and the AA sequences aligned and compared to a reference sequence. Treatment emergent (TE) substitutions are defined as AA differences in a post-Baseline sample that were not present at Baseline at the defined threshold for minority and consensus analysis. The number of participants with TE substitutions in the spike protein reflects participants that had a TE change in the spike protein at any position including the sotrovimab epitope. AA substitutions compared to the reference strain are presented at Day 7.
Number of Participants With Treatment Emergent Amino Acid Substitutions >5% and >50% Allelic Frequency in the Spike Protein at Day 14	At Day 14	SARS-CoV-2 spike analysis was carried out by nucleotide sequencing of the SARS-CoV-2 spike protein by NGS analysis of participant nasal/oropharyngeal swab samples. The nucleotide sequences were translated, and the AA sequences aligned and compared to a reference sequence. Treatment emergent (TE) substitutions are defined as AA differences in a post-Baseline sample that were not present at Baseline at the defined threshold for minority and consensus analysis. The number of participants with TE substitutions in the spike protein reflects participants that had a TE change in the spike protein at any position including the sotrovimab epitope. AA substitutions compared to the reference strain are presented at Day 14.
Number of Participants With Treatment Emergent Amino Acid Substitutions >5% and >50% Allelic Frequency in the Spike Protein at Day 28	At Day 28	SARS-CoV-2 spike analysis was carried out by nucleotide sequencing of the SARS-CoV-2 spike protein by NGS analysis of participant nasal/oropharyngeal swab samples. The nucleotide sequences were translated, and the AA sequences aligned and compared to a reference sequence. Treatment emergent (TE) substitutions are defined as AA differences in a post-Baseline sample that were not present at Baseline at the defined threshold for minority and consensus analysis. The number of participants with TE substitutions in the spike protein reflects participants that had a TE change in the spike protein at any position including the sotrovimab epitope. AA substitutions compared to the reference strain are presented at Day 28.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Variants of Concern (VOC) or Variants Under Investigation (VUI)	Up to Day 28	SARS-CoV-2 VOC is defined by World health Organization(WHO) that meets definition of VUI and through a comparative assessment, has been demonstrated to be associated with 1 or more of following changes at degree of global public health(GPH) significance: increase in transmissibility or detrimental change in COVID-19 epidemiology, OR increase in virulence or change in clinical disease presentation, OR decrease in effectiveness of public health and social measures or available diagnostics, vaccines, therapeutics. SARS-CoV-2 VUI is defined by WHO as a variant:with genetic changes that are predicted or known to affect virus characteristics such as transmissibility, disease severity, immune, diagnostic or therapeutic escape and identified to cause significant community transmission or multiple COVID-19 clusters, in multiple countries with increasing relative prevalence alongside increasing number of cases over time, or other apparent epidemiological impacts to suggest emerging risk to GPH.
Number of Participants With Undetectable Virus by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)	At Day 7, Day 14, and Day 28	The number of participants that had undetectable viral load in nasal/oropharyngeal swabs was determined by quantitative reverse transcription-polymerase chain reaction (qRT/PCR) at Day 7, Day 14, and Day 28. Participants with major protocol deviation (out of visit window/samples received late/return more samples than expected) at specific visits were excluded from analysis.
Number of Participants With All Cause Hospital Stay	Up to Day 28	Number of participants hospitalized due to any cause have been reported.
Number of Participants With COVID-19 Related Hospital Stay	Up to Day 28	Number of participants hospitalized due to COVID-19 have been reported.
Number of Participants Requiring New or Increased Oxygen Support (Supplemental Oxygen [Not High Flow]), Non-invasive Ventilation or High-flow, Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO)	Up to Day 28	Number of participants required new or increased oxygen support (supplemental oxygen \[not high flow\]), non-invasive ventilation or high-flow, invasive mechanical ventilation or ECMO have been reported.
Number of Participants With All Cause Intensive Care Unit (ICU) Hospital Stay	Up to Day 28	Number of participants hospitalized in ICU due to any cause have been reported.
Number of Participants With COVID-19 Related ICU Hospital Stay	Up to Day 28	Number of participants hospitalized in ICU due to COVID-19 have been reported.
Number of Participants Who Died Due to Any Cause Through Day 28	Up to Day 28	Data for number of participants who died due to any cause through Day 28 have been reported.
Number of Participants Who Died Due to COVID-19 Through Day 28	Up to Day 28	Data for number of participants who died due to COVID-19 have been reported.
Number of Participants With Treatment-emergent Amino Acid Substitutions in the Spike Protein for Any Substitutions at Allelic Frequency >5%	At Day 7, Day 14 and Day 28	SARS-CoV-2 spike analysis was carried out by nucleotide sequencing of the SARS-CoV-2 spike protein by NGS analysis of participant nasal/oropharyngeal swab samples for samples above the threshold for the sequencing assay. The nucleotide sequences were translated, and the AA sequences aligned and compared to a reference sequence. For samples with AA changes above the \>5% threshold for allelic frequency determination, AA changes in SARS-CoV-2 spike protein compared to Baseline was reported. One participant may have more than one substitution under the same codon. Treatment Emergent Substitutions included participants where a Baseline and post-Baseline records exist. All type of AA mutations have been categorized.
Number of Participants With Treatment-emergent Amino Acid Substitutions in the Spike Protein for Any Substitutions at Allelic Frequency >50%	At Day 7, Day 14 and Day 28	SARS-CoV-2 spike analysis was carried out by nucleotide sequencing of the SARS-CoV-2 spike protein by NGS analysis of participant nasal/oropharyngeal swab samples for samples with viral load above the threshold of the sequencing assay. The nucleotide sequences were translated, and the AA sequences aligned and compared to a reference sequence. For samples with AA changes above the threshold for consensus sequence generation that were not present in the Baseline sequence, AA changes in the SARS-CoV-2 spike protein consensus sequence (\>50%) from Baseline was reported. One participant may have more than one substitution under the same codon. Treatment Emergent Substitutions included participants where a Baseline and post-Baseline records exist. All type of AA mutations have been categorized.