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

• ClinicalTrials.gov Identifier: NCT05135650
• Recruitment Status: Suspended
• First Posted: November 26, 2021
• Last Update Posted: January 26, 2023
• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: National Marrow Donor Program; Vir Biotechnology, Inc.
• Information provided by (Responsible Party): Fred Hutchinson Cancer Center

Tracking Information

• First Submitted Date: November 23, 2021
• First Posted Date: November 26, 2021
• Last Update Posted Date: January 26, 2023
• Actual Study Start Date: January 25, 2022
• Estimated Primary Completion Date: January 15, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 23, 2021)

• Half-life of sotrovimab (VIR-7831) post-transplant [ Time Frame: Up to 24 weeks ]
  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.
• Neutralizing antibody titers [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 23, 2021)

• Half-life of VIR-7831 in matched versus mis-matched donors [ Time Frame: Up to 24 weeks ]
  Comparisons will be tested using a t-test.
• Half-life of VIR-7831 in autologous vs allogeneic HCT [ Time Frame: Up to 24 weeks ]
  Comparisons will be tested using a t-test.
• Half-life of VIR-7831 in patients with diarrhea vs no diarrhea [ Time Frame: Up to 24 weeks ]
  Comparisons will be tested using a t-test.
• Half-life of VIR-7831 in patients with and without graft versus host disease [ Time Frame: Up to 24 weeks ]
  Comparisons will be tested using a t-test.
• Frequency of breakthrough SARS-CoV-2 acquisition [ Time Frame: Up to 24 weeks ]
  Will monitor for breakthrough SARS-CoV-2 infection by polymerase chain reaction of fluid collected by nasal swabs.
• Antibody levels from serum/plasma [ Time Frame: At 12, 16, 20 and 24 weeks ]
  Will compare antibody levels from serum/plasma collected by venipuncture versus self-collected using a TASSO device and fluid from nasal swabs.
• Anti-drug antibody levels from serum/plasma [ Time Frame: At 12, 16, 20 and 24 weeks (and week 40 if positive at week 24) ]
  Will monitor for anti-drug antibody levels from serum/plasma collected by venipuncture versus self-collected using a TASSO device
• Incidence of adverse events [ Time Frame: Up to 40 weeks ]
  Will monitor safety with routine labs as part of standard post-transplant care.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pharmacokinetics of Sotrovimab as Pre-exposure Prophylaxis for COVID-19 in Hematopoietic Stem Cell Transplant Recipients, COVIDMAB Study
• Official Title: Pharmacokinetics of a SARS-CoV-2 Monoclonal Antibody in Hematopoietic Stem Cell Transplant Recipients (COVIDMAB)
• 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.

After completion of study treatment, patients are followed up for 24 weeks.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Prevention

Condition

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

Intervention

• Other: Questionnaire Administration
  Ancillary studies
• Biological: Sotrovimab
  Given IV
  Other Names:

  • Anti-SARS-CoV-2 Spike Protein Monoclonal Antibody VIR-7831
  • GSK 4182136
  • GSK-4182136
  • GSK4182136
  • VIR 7831
  • VIR-7831
  • VIR7831
  • Monoclonal antibodies against SARS-CoV-2: sotrovimab

Study Arms

Experimental: Prevention (Sotrovimab)

Patients receive sotrovimab IV over 30 minutes within 1-7 days prior to the start of pre-transplant conditioning.

Interventions:

• Other: Questionnaire Administration
• Biological: Sotrovimab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Suspended
• Estimated Enrollment (submitted: June 6, 2022): 55
• Original Estimated Enrollment (submitted: November 23, 2021): 50
• Estimated Study Completion Date: January 15, 2024
• Estimated Primary Completion Date: January 15, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05135650
• Other Study ID Numbers: RG1121602; NCI-2021-05949 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 10691 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Fred Hutchinson Cancer Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Fred Hutchinson Cancer Center
• Original Study Sponsor: Same as current

Collaborators

• National Marrow Donor Program
• Vir Biotechnology, Inc.

Investigators

• Principal Investigator: Alpana Waghmare; Fred Hutch/University of Washington Cancer Consortium

• PRS Account: Fred Hutchinson Cancer Center
• Verification Date: January 2023