COVID-19 Infection, Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm
Conditions
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.
Interventions
OTHERQuestionnaire Administration
Ancillary studies
BIOLOGICALSotrovimab
Given IV
PROCEDUREBiospecimen Collection
Undergo blood and nasal swab sample collection
Sponsors
National Marrow Donor Program
Vir Biotechnology, Inc.
Fred Hutchinson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sotrovimab Patients receive sotrovimab IV over 30 minutes within 1-7 days prior to the start of pre-transplant conditioning. Patients complete questionnaires, blood sample, and nasal swab collections throughout course of trial. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Sotrovimab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Conditioning regimen Bu/Cy | 1 Participants |
| Conditioning regimen Bu/Cy/Thiotepa | 1 Participants |
| Conditioning regimen Bu/Cy/Thiotepa/Palifermin | 1 Participants |
| Conditioning regimen CLAG-M/TBI | 1 Participants |
| Conditioning regimen Flu/Cy/TBI | 1 Participants |
| Conditioning regimen Flu/Cy/Thiotepa/TBI | 1 Participants |
| Conditioning regimen Flu/Mel | 2 Participants |
| Conditioning regimen Flu/Mel/TBI | 5 Participants |
| Conditioning regimen Flu/TBI | 3 Participants |
| Conditioning regimen Flu/Treo | 1 Participants |
| Conditioning regimen Mel | 3 Participants |
| Diagnosis Acute leukemia | 5 Participants |
| Diagnosis Lymphoma | 3 Participants |
| Diagnosis MDS | 5 Participants |
| Diagnosis MPN (CMML, MF) | 3 Participants |
| Diagnosis Multiple myeloma | 3 Participants |
| Diagnosis T-LGL | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 14 Participants |
| Type of transplant Allogeneic cord blood | 2 Participants |
| Type of transplant Allogeneic matched related | 4 Participants |
| Type of transplant Allogeneic matched unrelated | 8 Participants |
| Type of transplant Allogeneic mismatched unrelated | 1 Participants |
| Type of transplant Autologous | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 20 |
| other Total, other adverse events | 3 / 20 |
| serious Total, serious adverse events | 1 / 20 |
Outcome results
Primary
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotrovimab | Half-life of Sotrovimab (VIR-7831) Post-transplant | 51.14 Days | Standard Deviation 18.59 |
Primary
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
Population: Neutralization assays were not performed, thus no data was collected.
Secondary
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
Population: Only those participants with data available at the specified time points were analyzed. Due to early termination, we did not analyze TASSO samples or nasal swabs, hence there is no TASSO or nasal swab data to report.~Two different groups were analyzed based on transplant type. The number of patients in each subgroup will add up to the total number of patients analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sotrovimab | Antibody Clearance Rate From Serum/Plasma | Elimination clearance in autologous HCT participants | 0.1074 L/day | Standard Deviation 0.0141 |
| Sotrovimab | Antibody Clearance Rate From Serum/Plasma | Elimination clearance in allogeneic HCT participants | 0.1462 L/day | Standard Deviation 0.0479 |
Secondary
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
Population: Two different groups were analyzed based on transplant type. The number of participants in each subgroup will add up to the total number of participants analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sotrovimab | Half-life of VIR-7831 in Autologous vs Allogeneic HCT | Half-life in autologous participants | 63.9 Days |
| Sotrovimab | Half-life of VIR-7831 in Autologous vs Allogeneic HCT | Half-life in allogeneic participants | 49.4 Days |
Secondary
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
Population: There was only 1 participant in the mismatched group, therefore, sample size was too small to calculate and compare mean or median half-lives between groups. Thus, half-life data was not collected on these groups.
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sotrovimab | Number of Participants With Adverse Events | 4 Participants |
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sotrovimab | Number of Participants With Breakthrough SARS-CoV-2 Acquisition | 3 Participants |
Secondary
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
Population: Only blood collected by venipuncture was assessed. Blood was rarely collected using the TASSO device due to participants declining TASSO use, sotrovimab deauthorization, and early study termination. Limited blood collection with TASSO device, premature study closure, and lack of funds prevented planned laboratory assays on blood collected with the TASSO device. Thus, no laboratory data is available from TASSO-collected blood and no analysis was performed. Further data collection is not planned.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sotrovimab | Number of Participants With Presence of Anti-drug Antibodies From Serum/Plasma | Baseline with positive test results | 0 Participants |
| Sotrovimab | Number of Participants With Presence of Anti-drug Antibodies From Serum/Plasma | Week 4 with positive test results | 0 Participants |
| Sotrovimab | Number of Participants With Presence of Anti-drug Antibodies From Serum/Plasma | Week 24 with positive test results | 0 Participants |
Secondary
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
Population: Three different groups were analyzed based on transplant type and presence of lower GI GVHD. The number of patients in each subgroup will add up to the total number of patients analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sotrovimab | VIR-7831 Exposure in Patients With and Without Graft Versus Host Disease | Allogeneic HCT with lower GI GVHD | 1846.97 (AUC) micrograms x day/mL | Standard Deviation 315.84 |
| Sotrovimab | VIR-7831 Exposure in Patients With and Without Graft Versus Host Disease | Allogeneic HCT without lower GI GVHD | 3613.94 (AUC) micrograms x day/mL | Standard Deviation 392.81 |
| Sotrovimab | VIR-7831 Exposure in Patients With and Without Graft Versus Host Disease | Autologous HCT without lower GI GVHD | 4146.8 (AUC) micrograms x day/mL | Standard Deviation 397.57 |
Secondary
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
Population: Three different groups were analyzed based on transplant type and presence of diarrhea. The number of patients in each subgroup will add up to the total number of patients analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sotrovimab | VIR-7831 Exposure in Patients With Diarrhea vs no Diarrhea | Allogeneic HCT with diarrhea | 2027.48 (AUC) micrograms x day/mL | Standard Deviation 348.84 |
| Sotrovimab | VIR-7831 Exposure in Patients With Diarrhea vs no Diarrhea | Allogeneic HCT without diarrhea | 3613.94 (AUC) micrograms x day/mL | Standard Deviation 392.81 |
| Sotrovimab | VIR-7831 Exposure in Patients With Diarrhea vs no Diarrhea | Autologous HCT without diarrhea | 4146.8 (AUC) micrograms x day/mL | Standard Deviation 397.57 |