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

NCT05305651 | Completed Phase 4 Results

• 1 other identifier: 218407
• Study Type: interventional
• Target: 217
• Locations: 1 country
• Sites: 8

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.

Conditions

COVID-19

Keywords

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

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (11)

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

  Up to Day 28

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

  At Day 7, Day 14, and Day 28

• Number of Participants With All Cause Hospital Stay

  Up to Day 28

• Number of Participants With COVID-19 Related Hospital Stay

  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)

  Up to Day 28

Study Arms (1)

Participants receiving Sotrovimab

EXPERIMENTAL

Immunocompromised non-hospitalized participants will receive sotrovimab as standard of clinical care for COVID-19 in sentinel sites

Drug: Sotrovimab

Interventions

Sotrovimab DRUG

Sotrovimab dose and administration per standard of clinical care

Participants receiving Sotrovimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (8)

GSK Investigational Site

Cambridge, CB2 0QQ, United Kingdom

Location

GSK Investigational Site

Cardiff, CF14 4XW, United Kingdom

Location

GSK Investigational Site

EdgbastonBirmingham, B15 2GW, United Kingdom

Location

GSK Investigational Site

London, NW1 2BU, United Kingdom

Location

GSK Investigational Site

London, SE1 7EH, United Kingdom

Location

GSK Investigational Site

Middlesbrough, TS4 3BW, United Kingdom

Location

GSK Investigational Site

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

GSK Investigational Site

Plymouth, PL6 5FP, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 35780162 BACKGROUND

MeSH Terms

Conditions

COVID-19

Interventions

sotrovimab

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 30, 2022
• First Posted: March 31, 2022
• Study Start: July 1, 2022
• Primary Completion: July 17, 2023
• Study Completion: July 17, 2023
• Last Updated: October 15, 2024
• Results First Posted: October 15, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

GB (8)