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

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

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 Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Sotrovimab

• Study Type: Interventional
• Enrollment (Actual): 217
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • GSK Investigational Site
  • Cardiff, United Kingdom, CF14 4XW
    • GSK Investigational Site
  • EdgbastonBirmingham, United Kingdom, B15 2GW
    • GSK Investigational Site
  • London, United Kingdom, SE1 7EH
    • GSK Investigational Site
  • London, United Kingdom, NW1 2BU
    • GSK Investigational Site
  • Middlesbrough, United Kingdom, TS4 3BW
    • GSK Investigational Site
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • GSK Investigational Site
  • Plymouth, United Kingdom, PL6 5FP
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants receiving Sotrovimab; Immunocompromised non-hospitalized participants will receive sotrovimab as standard of clinical care for COVID-19 in sentinel sites	Drug: Sotrovimab; Sotrovimab dose and administration per standard of clinical care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	At Day 14
Number of Participants With Treatment Emergent Amino Acid Substitutions >5% and >50% Allelic Frequency in the Sotrovimab Epitope 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.	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.	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.	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.	At Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	Up to Day 28
Number of Participants With COVID-19 Related Hospital Stay	Number of participants hospitalized due to COVID-19 have been reported.	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 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.	Up to Day 28
Number of Participants With All Cause Intensive Care Unit (ICU) Hospital Stay	Number of participants hospitalized in ICU due to any cause have been reported.	Up to Day 28
Number of Participants With COVID-19 Related ICU Hospital Stay	Number of participants hospitalized in ICU due to COVID-19 have been reported.	Up to Day 28
Number of Participants Who Died Due to Any Cause Through Day 28	Data for number of participants who died due to any cause through Day 28 have been reported.	Up to Day 28
Number of Participants Who Died Due to COVID-19 Through Day 28	Data for number of participants who died due to COVID-19 have been reported.	Up to Day 28
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.	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.	At Day 7, Day 14 and Day 28

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Publications and helpful links

General Publications

• Case JB, Mackin S, Errico JM, Chong Z, Madden EA, Whitener B, Guarino B, Schmid MA, Rosenthal K, Ren K, Dang HV, Snell G, Jung A, Droit L, Handley SA, Halfmann PJ, Kawaoka Y, Crowe JE Jr, Fremont DH, Virgin HW, Loo YM, Esser MT, Purcell LA, Corti D, Diamond MS. Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains. Nat Commun. 2022 Jul 2;13(1):3824. doi: 10.1038/s41467-022-31615-7.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Actual): July 17, 2023
• Study Completion (Actual): July 17, 2023

Study Registration Dates

• First Submitted: March 30, 2022
• First Submitted That Met QC Criteria: March 30, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: July 10, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Monoclonal antibody; Pandemic; SARS CoV-2; Sotrovimab; Coronavirus disease 2019 (COVID-19); LUNAR; Immunocompromised (IC)
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Anti-Infective Agents; Antiviral Agents; Sotrovimab
• Other Study ID Numbers: 218407

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No