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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2021-05949 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 10691 | Other Identifier | Fred Hutch/University of Washington Cancer Consortium |
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Terminated due to FDA withdrawal of the emergency use authorization (EUA) for sotrovimab
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| Name | Class |
|---|---|
| National Marrow Donor Program | OTHER |
| Vir Biotechnology, Inc. | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Questionnaire Administration | Other | Ancillary studies |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to 24 weeks |
| Half-life of VIR-7831 in Autologous vs Allogeneic HCT |
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Inclusion Criteria:
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)
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
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| Name | Affiliation | Role |
|---|---|---|
| Alpana Waghmare | Fred Hutch/University of Washington Cancer Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fred Hutch/University of Washington Cancer Consortium | Seattle | Washington | 98109 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 17, 2023 |
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| Sotrovimab |
| Biological |
Given IV |
|
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| Biospecimen Collection | Procedure | Undergo blood and nasal swab sample collection |
|
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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. |
| 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. | 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. | 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. | 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. | 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. | At 4 and 24 weeks |
| Number of Participants With Adverse Events | Will monitor safety with routine labs as part of standard post-transplant care. | Up to 40 weeks |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Diagnosis | Count of Participants | Participants |
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| Conditioning regimen | Conditioning regimens are determined by clinical teams. Data is collected through chart review. Abbreviations: Bu, busulfan; CLAG-M, cladribine + cytarabine + granulocyte colony-stimulating factor + mitoxantrone; CMML, chronic myelomonocytic leukemia; Cy, cyclophosphamide; Flu, fludarabine; MDS, myelodysplastic syndrome; Mel, melphalan; MF, myelofibrosis; MPN, myeloproliferative neoplasm; TBI, total body irradiation; T-LGL, T-cell large granular lymphocytic leukemia; Treo, treosulfan. | Count of Participants | Participants |
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| Type of transplant | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Deviation | Days | Up to 24 weeks |
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| 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. | Neutralization assays were not performed, thus no data was collected. | Posted | Up to 24 weeks |
|
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| 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. | 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. | Posted | Up to 24 weeks |
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| 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. | 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. | Posted | Median | 90% Confidence Interval | Days | Up to 24 weeks |
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| 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. | 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. | Posted | Mean | Standard Deviation | (AUC) micrograms x day/mL | Up to 24 weeks |
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| 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. | 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. | Posted | Mean | Standard Deviation | (AUC) micrograms x day/mL | Up to 24 weeks |
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| 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. | Posted | Count of Participants | Participants | Up to 24 weeks |
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| 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. | 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. | Posted | Mean | Standard Deviation | L/day | Up to 24 weeks |
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| 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. | 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. | Posted | Count of Participants | Participants | At 4 and 24 weeks |
| ||||||||||||||||||||||||||||
| Secondary | Number of Participants With Adverse Events | Will monitor safety with routine labs as part of standard post-transplant care. | Posted | Count of Participants | Participants | Up to 40 weeks |
|
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10 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 1 | 20 | 1 | 20 | 3 | 20 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Death | Gastrointestinal disorders | Systematic Assessment | Gastrointestinal hemorrhage is cause of death. Determined to not be related to investigation product. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypertension stage 2 | Cardiac disorders | Systematic Assessment | Occurred following infusion or day after infusion. Unknown if related to investigation product. |
| |
| Tingling | Injury, poisoning and procedural complications | Systematic Assessment | Tingling of arms and chest during product infusion. Paused infusion and improved without additional intervention. Unknown if related to product infusion. |
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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.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Alpana Waghmare (Study Principal Investigator) | Fred Hutch/University of Washington Cancer Consortium | 206-667-7329 | awaghmar@fredhutch.org |
| May 24, 2024 |
| Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 24, 2022 | Jun 8, 2023 | ICF_000.pdf |
| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D019337 | Hematologic Neoplasms |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D014777 | Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C000711967 | sotrovimab |
| D013048 | Specimen Handling |
| ID | Term |
|---|---|
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D008919 | Investigative Techniques |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| MDS |
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| MPN (CMML, MF) |
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| Lymphoma |
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| Multiple myeloma |
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| Flu/Treo |
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| Flu/TBI |
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| Bu/Cy |
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| Flu/Mel/TBI |
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| Flu/Cy/TBI |
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| Bu/Cy/Thiotepa |
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| Bu/Cy/Thiotepa/Palifermin |
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| Flu/Cy/Thiotepa/TBI |
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| CLAG-M/TBI |
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| Allogeneic mismatched unrelated |
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| Allogeneic cord blood |
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| Autologous |
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