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

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05305651

Acronym

LUNAR

Enrollment

217

Registered

2022-03-31

Start date

2022-07-01

Completion date

2023-07-17

Last updated

2024-10-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

COVID-19

Keywords

SARS CoV-2, LUNAR, Coronavirus disease 2019 (COVID-19), Pandemic, Sotrovimab, Monoclonal antibody, Immunocompromised (IC)

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.

Interventions

DRUGSotrovimab

Sotrovimab dose and administration per standard of clinical care

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Intervention 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.

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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 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 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.
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 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.

Countries

United Kingdom

Participant flow

Recruitment details

This was a prospective cohort study amongst immunocompromised non-hospitalized participants treated with sotrovimab as part of standard clinical care to monitor the emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike viral variants.

Pre-assignment details

A total of 217 participants were enrolled in this study.

Participants by arm

Arm	Count
Sotrovimab 500 mg IV Immunocompromised non-hospitalized participants were treated with sotrovimab 500 milligram (mg) intravenously (IV) as a standard of clinical care for Coronavirus Disease 2019 (COVID-19).	217
Total	217

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Death	1
Overall Study	Lost to Follow-up	4
Overall Study	Withdrawal by Subject	4

Baseline characteristics

Characteristic	Sotrovimab 500 mg IV
Age, Continuous	56.5 Years STANDARD_DEVIATION 15.66
Race/Ethnicity, Customized De-identified	29 Participants
Race/Ethnicity, Customized White	49 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	139 Participants
Sex: Female, Male Female	123 Participants
Sex: Female, Male Male	94 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	1 / 217
other Total, other adverse events	6 / 217
serious Total, serious adverse events	0 / 217

Outcome results

Primary

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

Population: The Safety Set included all participants who were enrolled and exposed to study intervention. Only those participants with Paired Sequences were included in the analysis. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the Overall Number of Participants Analyzed field.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Sotrovimab 500 mg IV	Number of Participants With Treatment Emergent Amino Acid Substitutions >5% and >50% Allelic Frequency in the Sotrovimab Epitope at Day 14	AA substitutions >5% allelic frequency	18 Participants
Sotrovimab 500 mg IV	Number of Participants With Treatment Emergent Amino Acid Substitutions >5% and >50% Allelic Frequency in the Sotrovimab Epitope at Day 14	AA substitutions >50% allelic frequency	11 Participants

Primary

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

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Sotrovimab 500 mg IV	Number of Participants With Treatment Emergent Amino Acid Substitutions >5% and >50% Allelic Frequency in the Sotrovimab Epitope at Day 28	AA substitutions >5% allelic frequency	11 Participants
Sotrovimab 500 mg IV	Number of Participants With Treatment Emergent Amino Acid Substitutions >5% and >50% Allelic Frequency in the Sotrovimab Epitope at Day 28	AA substitutions >50% allelic frequency	11 Participants

Primary

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

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Sotrovimab 500 mg IV	Number of Participants With Treatment Emergent Amino Acid Substitutions >5% and >50% Allelic Frequency in the Spike Protein at Day 14	AA substitutions >50% allelic frequency	17 Participants
Sotrovimab 500 mg IV	Number of Participants With Treatment Emergent Amino Acid Substitutions >5% and >50% Allelic Frequency in the Spike Protein at Day 14	AA substitutions >5% allelic frequency	37 Participants

Primary

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

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Sotrovimab 500 mg IV	Number of Participants With Treatment Emergent Amino Acid Substitutions >5% and >50% Allelic Frequency in the Spike Protein at Day 28	AA substitutions >5% allelic frequency	20 Participants
Sotrovimab 500 mg IV	Number of Participants With Treatment Emergent Amino Acid Substitutions >5% and >50% Allelic Frequency in the Spike Protein at Day 28	AA substitutions >50% allelic frequency	13 Participants

Primary

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

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Sotrovimab 500 mg IV	Number of Participants With Treatment Emergent Amino Acid Substitutions >5% and >50% Allelic Frequency in the Spike Protein at Day 7	AA substitutions >5% allelic frequency	88 Participants
Sotrovimab 500 mg IV	Number of Participants With Treatment Emergent Amino Acid Substitutions >5% and >50% Allelic Frequency in the Spike Protein at Day 7	AA substitutions >50% allelic frequency	19 Participants

Primary

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

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Sotrovimab 500 mg IV	Number of Participants With Treatment Emergent Amino Acid Substitutions Greater Than (>) 5 Percent (%) and >50% Allelic Frequency in the Sotrovimab Epitope at Day 7	AA substitutions >5% allelic frequency	38 Participants
Sotrovimab 500 mg IV	Number of Participants With Treatment Emergent Amino Acid Substitutions Greater Than (>) 5 Percent (%) and >50% Allelic Frequency in the Sotrovimab Epitope at Day 7	AA substitutions >50% allelic frequency	12 Participants

Secondary

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.

Time frame: Up to Day 28