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

Phase 1TerminatedNCT05135650

Fred Hutchinson Cancer Center20 enrolled

Overview

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.

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

Allocation

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: Up to 24 weeks

Secondary Outcomes

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

Comparisons will be tested using a t-test. Levels of VIR-7831 can be measured using an idiotypic antibody assay that is not affected by COVID-19 infection or vaccination.

Time frame: Up to 24 weeks

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

Comparisons will be tested using a t-test. Levels of VIR-7831 can be measured using an idiotypic antibody assay that is not affected by COVID-19 infection or vaccination.

Time frame: Up to 24 weeks

VIR-7831 Exposure in Patients With Diarrhea vs no Diarrhea

Sotrovimab exposure to be measured as the area under curve (AUC) of sotrovimab concentration over time in model simulation. Comparisons will be tested using a t-test.

Time frame: Up to 24 weeks

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

Sotrovimab exposure to be measured as the area under curve (AUC) of sotrovimab concentration over time. Comparisons will be tested using a t-test.

Time frame: Up to 24 weeks

Number of Participants With Breakthrough SARS-CoV-2 Acquisition

Will monitor for breakthrough SARS-CoV-2 infection by polymerase chain reaction of fluid collected by nasal swabs.

Time frame: Up to 24 weeks

Antibody Clearance Rate 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. To do this, will compare rate of antibody clearance on average in study population pharmacokinetic model.

Time frame: Up to 24 weeks

Number of Participants With Presence of Anti-drug Antibodies From Serum/Plasma

Will monitor for presence of anti-drug antibodies from serum/plasma collected by venipuncture versus self-collected using a TASSO device. Samples were considered either positive or negative for presence of anti-drug antibodies.

Time frame: At 4 and 24 weeks

Number of Participants With Adverse Events

Will monitor safety with routine labs as part of standard post-transplant care.

Time frame: Up to 40 weeks

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes