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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

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

Intervention / Treatment
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* Other: Questionnaire Administration
* Biological: Sotrovimab
* Procedure: Biospecimen Collection


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prevention (Sotrovimab)<br>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<br>* Ancillary studies<br>Biological: Sotrovimab<br>* Given IV<br>* Other names: Monoclonal antibodies against SARS-CoV-2: sotrovimab;Procedure: Biospecimen Collection<br>* Undergo blood and nasal swab sample collection<br>* Other names: Specimen Collection;|

What is the study measuring?
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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 |