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

GlaxoSmithKline217 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

217

Conditions

COVID-19

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (8)

GSK Investigational Site

Cambridge, United Kingdom

GSK Investigational Site

Cardiff, United Kingdom

GSK Investigational Site

EdgbastonBirmingham, United Kingdom

GSK Investigational Site

London, United Kingdom

GSK Investigational Site

London, United Kingdom

GSK Investigational Site

Middlesbrough, United Kingdom

GSK Investigational Site

Newcastle upon Tyne, United Kingdom

GSK Investigational Site

Plymouth, United Kingdom

Outcomes

Primary Outcomes

Number of Participants With Treatment Emergent Amino Acid Substitutions Greater Than (>) 5 Percent (%) and >50% Allelic Frequency in the Sotrovimab Epitope 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.

Time frame: At Day 7

Number of Participants With Treatment Emergent Amino Acid Substitutions >5% and >50% Allelic Frequency in the Sotrovimab Epitope 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.

Time frame: At Day 14

Number of Participants With Treatment Emergent Amino Acid Substitutions >5% and >50% Allelic Frequency in the Sotrovimab Epitope at Day 28

Time frame: At Day 28

Number of Participants With Treatment Emergent Amino Acid Substitutions >5% and >50% Allelic Frequency in the Spike Protein 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.

Time frame: At Day 7

Number of Participants With Treatment Emergent Amino Acid Substitutions >5% and >50% Allelic Frequency in the Spike Protein 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.

Time frame: At Day 14

Number of Participants With Treatment Emergent Amino Acid Substitutions >5% and >50% Allelic Frequency in the Spike Protein 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.

Time frame: At Day 28

Secondary Outcomes

Number of Participants With Variants of Concern (VOC) or Variants Under Investigation (VUI)

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.

Time frame: Up to Day 28

Number of Participants With Undetectable Virus by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)

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.

Time frame: At Day 7, Day 14, and Day 28

Number of Participants With All Cause Hospital Stay

Number of participants hospitalized due to any cause have been reported.

Time frame: Up to Day 28

Number of Participants With COVID-19 Related Hospital Stay

Number of participants hospitalized due to COVID-19 have been reported.

Time frame: Up to Day 28

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)

Number of Participants With Treatment-emergent Amino Acid Substitutions in the Spike Protein for Any Substitutions at Allelic Frequency >5%

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.

Time frame: At Day 7, Day 14 and Day 28

Number of Participants With Treatment-emergent Amino Acid Substitutions in the Spike Protein for Any Substitutions at Allelic Frequency >50%

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.

Time frame: At Day 7, Day 14 and Day 28