Pharmacokinetics of Sotrovimab as Pre-exposure Prophylaxis for COVID-19 in Hematopoietic Stem Cell Transplant Recipients, COVIDMAB Study

Pharmacokinetics of a SARS-CoV-2 Monoclonal Antibody in Hematopoietic Stem Cell Transplant Recipients (COVIDMAB)

This phase I trial studies the process by which sotrovimab is absorbed, distributed, metabolized, and eliminated by the body (pharmacokinetics) in hematopoietic stem cell transplant recipients. Sotrovimab is a monoclonal antibody that may target and bind to a specific protein on SARS-CoV-2 and block its viral attachment and entry into human cells. This may slow the progression of the disease and accelerate recovery, and may potentially provide temporary protection against infection with SARS-CoV-2 in hematopoietic stem cell transplant recipients.

Study Overview

• Status: Terminated
• Conditions: Hematopoietic and Lymphoid Cell Neoplasm; Malignant Solid Neoplasm; COVID-19 Infection
• Intervention / Treatment: Other: Questionnaire Administration; Biological: Sotrovimab; Procedure: Biospecimen Collection

Detailed Description

OUTLINE:

Patients receive sotrovimab intravenously (IV) over 30 minutes within 1-7 days prior to the start of pre-transplant conditioning. Patients also undergo blood and nasal swab sample collection throughout the trial.

After completion of study treatment, patients are followed up for 24 weeks.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients (or legally authorized representative if applicable) must be capable of understanding and providing a written informed consent
• Patients must be at least 18 years of age, of any gender, race, or ethnicity
• Patients must be undergoing HCT (any donor or stem cell source including autologous or cord blood)
• History of prior transplants are permitted
• History of COVID-19, history of vaccination for SARS-CoV-2, positive polymerase chain reaction (PCR) of a respiratory specimen for SARS-CoV-2 as long as it is not within four weeks from conditioning, or seropositivity for SARS-CoV-2 are permitted
• History of SARS-CoV-2 infection or vaccination of the donor are permitted.
• Post-enrollment vaccination is anticipated and permitted
• Administration of intravenous immunoglobulin therapy (IVIG) before or during the study is permitted

Exclusion Criteria:

• Signs or symptoms of uncontrolled, active infection
• Positive PCR result for SARS-CoV-2 within four weeks of scheduled conditioning

• Pregnant or breastfeeding (this population is generally not cleared for transplant)

  • Pregnancy test is obtained as part of pre-transplant evaluation in women of child-bearing potential at arrival to transplant and again within 7 days of conditioning and will be confirmed as negative by review of the chart
• Previous anaphylaxis or severe hypersensitivity reaction, including angioedema, to a mAb
• Previous reaction to a mAb that required medical attention
• Participants of other clinical studies that preclude the use of other investigational compounds
• Participants who, in the judgment of the investigator, will be unlikely or unable to comply with the requirements of the protocol or unlikely to survive to the end of study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• 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: Prevention (Sotrovimab); Patients receive sotrovimab IV over 30 minutes within 1-7 days prior to the start of pre-transplant conditioning. Patients also undergo blood and nasal swab sample collection throughout the trial.

Other: Questionnaire Administration; Ancillary studies; Biological: Sotrovimab; Given IV; Other Names: GSK4182136; Anti-SARS-CoV-2 Spike Protein Monoclonal Antibody VIR-7831; GSK 4182136; GSK-4182136; VIR 7831; VIR-7831; VIR7831; Monoclonal antibodies against SARS-CoV-2: sotrovimab; Procedure: Biospecimen Collection; Undergo blood and nasal swab sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Half-life of sotrovimab (VIR-7831) post-transplant	Will use descriptive statistics. Levels of VIR-7831 can be measured using an idiotypic antibody assay that is not affected by COVID-19 infection or vaccination.	Up to 24 weeks
Neutralizing antibody titers	Will be calculated by a one-phase exponential decay model. Will compare fold-changes in antibody titers by normalizing to pre-transplant levels for each subject.	Up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Half-life of VIR-7831 in matched versus mis-matched donors	Comparisons will be tested using a t-test.	Up to 24 weeks
Half-life of VIR-7831 in autologous vs allogeneic HCT	Comparisons will be tested using a t-test.	Up to 24 weeks
Half-life of VIR-7831 in patients with diarrhea vs no diarrhea	Comparisons will be tested using a t-test.	Up to 24 weeks
Half-life of VIR-7831 in patients with and without graft versus host disease	Comparisons will be tested using a t-test.	Up to 24 weeks
Frequency of breakthrough SARS-CoV-2 acquisition	Will monitor for breakthrough SARS-CoV-2 infection by polymerase chain reaction of fluid collected by nasal swabs.	Up to 24 weeks
Antibody levels from serum/plasma	Will compare antibody levels from serum/plasma collected by venipuncture versus self-collected using a TASSO device and fluid from nasal swabs.	At 12, 16, 20 and 24 weeks
Anti-drug antibody levels from serum/plasma	Will monitor for anti-drug antibody levels from serum/plasma collected by venipuncture versus self-collected using a TASSO device	At 12, 16, 20 and 24 weeks (and week 40 if positive at week 24)
Incidence of adverse events	Will monitor safety with routine labs as part of standard post-transplant care.	Up to 40 weeks

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: National Marrow Donor Program; Vir Biotechnology, Inc.
• Investigators: Principal Investigator: Alpana Waghmare, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2022
• Primary Completion (Actual): October 18, 2022
• Study Completion (Actual): January 10, 2023

Study Registration Dates

• First Submitted: November 23, 2021
• First Submitted That Met QC Criteria: November 23, 2021
• First Posted (Actual): November 26, 2021

Study Record Updates

• Last Update Posted (Actual): June 9, 2023
• Last Update Submitted That Met QC Criteria: June 8, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• 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; Neoplasms; COVID-19; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Sotrovimab
• Other Study ID Numbers: RG1121602; NCI-2021-05949 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 10691 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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