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

NCT05135650 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: RG1121602NCI-2021-0594910691
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

COVID-19 Infection; Hematopoietic and Lymphoid Cell Neoplasm; Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (2)

• Half-life of Sotrovimab (VIR-7831) Post-transplant

  Will use descriptive statistics of model estimation from population pharmacokinetic model. 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. Data analysis was not performed.

  Up to 24 weeks

Secondary Outcomes (8)

• Half-life of VIR-7831 in Matched vs Mismatched Donors

  Up to 24 weeks

• Half-life of VIR-7831 in Autologous vs Allogeneic HCT

  Up to 24 weeks

• VIR-7831 Exposure in Patients With Diarrhea vs no Diarrhea

  Up to 24 weeks

• VIR-7831 Exposure in Patients With and Without Graft Versus Host Disease

  Up to 24 weeks

• Number of Participants With Breakthrough SARS-CoV-2 Acquisition

  Up to 24 weeks

Study Arms (1)

Prevention (Sotrovimab)

EXPERIMENTAL

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; Biological: Sotrovimab; Procedure: Biospecimen Collection

Interventions

Questionnaire Administration OTHER

Ancillary studies

Prevention (Sotrovimab)

Sotrovimab BIOLOGICAL

Given IV

Also known as: Anti-SARS-CoV-2 Spike Protein Monoclonal Antibody VIR-7831, GSK 4182136, GSK-4182136, GSK4182136, VIR 7831, VIR-7831, VIR7831, Monoclonal antibodies against SARS-CoV-2: sotrovimab

Prevention (Sotrovimab)

Biospecimen Collection PROCEDURE

Undergo blood and nasal swab sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Prevention (Sotrovimab)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Marrow Donor Program: collaborator
• Vir Biotechnology, Inc.: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

COVID-19; Hematologic Neoplasms

Interventions

sotrovimab; Specimen Handling

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; Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Limitations and Caveats

Limitations due to small sample size: Relatively low precision in estimating covariate effects. Models/data presented focus on GI GVHD as cause of diarrhea; subgroup analysis couldn't be performed to examine whether different pretransplant preparative regimens were associated with increased mAb elimination. Did not perform covariate analysis on varying types of allogeneic HCT. Study halted prematurely due to emergence of variants with reduced in vitro neutralization to sotrovimab.

Results Point of Contact

• Title: Dr. Alpana Waghmare (Study Principal Investigator)
• Organization: Fred Hutch/University of Washington Cancer Consortium

awaghmar@fredhutch.org

206-667-7329

Study Officials

• Alpana Waghmare

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: November 23, 2021
• First Posted: November 26, 2021
• Study Start: January 25, 2022
• Primary Completion: October 18, 2022
• Study Completion: January 10, 2023
• Last Updated: February 13, 2025
• Results First Posted: February 13, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)