Pharmacokinetics of Sotrovimab as Pre-exposure Prophylaxis for COVID-19 in Hematopoietic Stem Cell Transplant Recipients, COVIDMAB Study
- Conditions
- Malignant Solid NeoplasmCOVID-19 InfectionHematopoietic and Lymphoid Cell Neoplasm
- Interventions
- Registration Number
- NCT05135650
- Lead Sponsor
- Fred Hutchinson Cancer Center
- 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.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 20
- 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
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Signs or symptoms of uncontrolled, active infection
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Positive PCR result for SARS-CoV-2 within four weeks of scheduled conditioning
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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
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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
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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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Prevention (Sotrovimab) 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. Prevention (Sotrovimab) Questionnaire Administration 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. Prevention (Sotrovimab) Biospecimen Collection 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.
- Primary Outcome Measures
Name Time Method Half-life of Sotrovimab (VIR-7831) Post-transplant Up to 24 weeks 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.
Neutralizing Antibody Titers Up to 24 weeks 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.
- Secondary Outcome Measures
Name Time Method Half-life of VIR-7831 in Matched vs Mismatched Donors Up to 24 weeks 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.
Half-life of VIR-7831 in Autologous vs Allogeneic HCT Up to 24 weeks 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.
VIR-7831 Exposure in Patients With Diarrhea vs no Diarrhea Up to 24 weeks 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.
VIR-7831 Exposure in Patients With and Without Graft Versus Host Disease Up to 24 weeks Sotrovimab exposure to be measured as the area under curve (AUC) of sotrovimab concentration over time. Comparisons will be tested using a t-test.
Number of Participants With Breakthrough SARS-CoV-2 Acquisition Up to 24 weeks Will monitor for breakthrough SARS-CoV-2 infection by polymerase chain reaction of fluid collected by nasal swabs.
Antibody Clearance Rate From Serum/Plasma Up to 24 weeks 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.
Number of Participants With Presence of Anti-drug Antibodies From Serum/Plasma At 4 and 24 weeks 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.
Number of Participants With Adverse Events Up to 40 weeks Will monitor safety with routine labs as part of standard post-transplant care.
Trial Locations
- Locations (1)
Fred Hutch/University of Washington Cancer Consortium
🇺🇸Seattle, Washington, United States