A Safety and Tolerability Study of Sotrovimab (VIR-7831) Prophylaxis Against COVID-19 in Immunocompromised Individuals

NCT ID: NCT05210101

Last Updated: 2024-08-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 93 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-07
• Study Completion Date: 2023-02-28

Brief Summary

This is an open-label study examining the safety and tolerability of sotrovimab, administered in two sequential doses as prophylaxis in immunocompromised patients with impaired humoral immunity against SARS-CoV-2.

Detailed Description

This open-label study evaluated the safety and tolerability of sotrovimab, administered in two sequential doses, as COVID-19 prophylaxis in immunocompromised patients with impaired humoral immunity against SARS-CoV-2. 93 patients were enrolled in this study, 10 patients in an initial lead-in PK cohort initially planned to determine the optimal dosing interval between the first and second dose of sotrovimab and assess the safety and tolerability of the drug (prior to the spread of the BA.2 variant, which made it necessary to administer the repeat sotrovimab dose earlier than originally anticipated, using theoretical modeling and logistical considerations), 50 patients (including the 10 patients in the lead-in PK cohort) in a safety and tolerability lead-in cohort to examine rates of infusion-related reactions (IRR) with a 30-minute sotrovimab IV infusion, and the remainder in an expansion cohort for further assessment of the safety and tolerability of sotrovimab in this patient population, with the sotrovimab infusion duration determined by the rate of IRRs in the 50-patient safety and tolerability lead-in cohort. The first treatment consisted of sotrovimab 500mg as an intravenous (IV) infusion over 30 minutes, followed by a one-hour monitoring period. The second treatment, administered in a time when BA.2 became the dominant SARS-CoV-2 variant, consisted of sotrovimab 2000mg as an intravenous (IV) infusion over 60 minutes, followed by a two-hour monitoring period in the first 10 patients administered this dose, who comprised a second lead-in safety cohort for this 2000mg dose, and a one-hour monitoring period in all patients subsequently receiving their second sotrovimab dose, maintaining this one-hour monitoring period as long as there were no grade >2 infusion-related reactions or other SAEs potentially related to the sotrovimab dose in this 2000mg dose lead-in safety cohort.

Conditions

SARS CoV 2 Infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Sotrovimab

Two intravenous (IV) doses of sotrovimab were be administered in total - the first on Treatment Day 1 (500mg) and the second on Treatment Day 2, approximately 8-14 weeks after the first dose, at a higher 2000mg dose, in light of the reduced antiviral susceptibility of the BA.2 subvariant to sotrovimab, with the dosing interval determined by theoretical modeling of the duration of efficacy of sotrovimab as antiviral prophylaxis based on the rising prevalence of the Omicron BA.2 subvariant.

Group Type: OTHER

Sotrovimab

Intervention Type: DRUG

Two intravenous (IV) doses of sotrovimab were administered over the study period, the first 500mg, and the second 2000mg, in light of the reduced antiviral neutralization of sotrovimab against the BA.2 subvariant.

Interventions

Sotrovimab

Two intravenous (IV) doses of sotrovimab were administered over the study period, the first 500mg, and the second 2000mg, in light of the reduced antiviral neutralization of sotrovimab against the BA.2 subvariant.

Intervention Type: DRUG

Other Intervention Names

VIR-7831

Eligibility Criteria

Inclusion Criteria

• Participant must be 18 years of age or older at the time of consent and weigh at least 40 kg. Children will be excluded from this study because dosing and adverse event data are limited for the use of sotrovimab in participants <18 years of age.
• Participant must have one of the following immunocompromising conditions that increases their likelihood of having an impaired humoral immune response to SARS-CoV-2, while also increasing their risk of being infected with SARS-CoV-2 and risk of progression to severe COVID-19:

1. Exposure to an anti-CD20 monoclonal antibody (e.g. all formulations of rituximab, obinutuzumab, ofatumumab, ocrelizumab, ibritumomab, tositumomab) for a hematologic malignancy or an autoimmune/inflammatory disease in the 12-month period prior to consent.

2. Allogeneic hematopoietic cell transplant ≥ 3 months and ≤ 1 year prior to consent; or allogeneic hematopoietic cell transplant >1 year prior to consent plus active graft-versus host disease on systemic immunosuppressive therapy.

3. Chimeric antigen receptor (CAR)-T cell therapy ≥ 4 weeks and ≤ 2 years prior to consent.

4. Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), multiple myeloma, or Waldenström macroglobulinemia.

5. Solid organ transplant recipient receiving immunosuppressive therapy.

6. Congenital immunodeficiency syndrome (e.g. Wiskott-Aldrich syndrome, DiGeorge syndrome, common variable immunodeficiency).

7. Patients with hematologic malignancy or autoimmune/inflammatory disease exposed to immunosuppressive medications specifically associated with a blunted humoral immune response to SARS-CoV-2 vaccination (e.g. mycophenolate mofetil, azathioprine, methotrexate, Bruton tyrosine kinase inhibitors, ruxolitinib, venetoclax, or corticosteroids (prednisone >20mg or equivalent daily for at least 14 days) in the 3-month period prior to consent.

• Female participants must be:

1. Postmenopausal for at least 1 year;

2. Post-hysterectomy and/or post-bilateral oophorectomy;

3. Of childbearing potential, with a negative urine or serum human chorionic gonadotropin pregnancy test prior to each sotrovimab dose, and agree to use a highly effective method of birth control throughout the study period.

• Participants must have a negative or low-positive (<50 U/mL) SARS-CoV-2 spike antibody assay result within 28 days of consent.

Exclusion Criteria

• Participants with an active SARS-CoV-2 infection, with a positive SARS-CoV-2 RT-PCR or antigen test result within 21 days prior to consent.
• Participants with symptoms suggestive of SARS-CoV-2 infection.
• Close contact (less than 6 feet away for a cumulative total of ≥ 15 minutes over a 24-hour period) with an individual with COVID-19 in the 14 days prior to consent.
• Individuals who are pregnant or breastfeeding.
• Participants who are receiving any other investigational agents.
• Participants who, in the judgment of the investigator, are likely to have a life expectancy of less than one year.
• Known hypersensitivity to any constituent present in sotrovimab or any other anti-SARSCoV-2 monoclonal antibody product.
• Active enrollment on another interventional research study of any agent for the treatment or prophylaxis of SARS-CoV-2 infection.
• Exposure to any other anti-SARS-CoV-2 monoclonal antibody product for the treatment of COVID-19 in the prior 6 months.
• Exposure to any other anti-SARS-CoV-2 monoclonal antibody product for prophylaxis against COVID-19 infection in the prior 12 months.
• Receipt of a SARS-CoV-2 vaccine dose within the prior 28 days.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Sophia Koo, M.D.

OTHER

Sponsor Role: lead

Responsible Party

Sophia Koo, M.D.

Sponsor-Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Sophia Koo, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber/Brigham and Women's Cancer Center

Jennifer Manne-Goehler, MD, ScD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Sarah P Hammond, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Countries

United States

References

Gonzalez-Bocco IH, Beluch K, Cho A, Lahoud C, Reyes FA, Moshovitis DG, Unger-Mochrie GM, Wang W, Hammond SP, Manne-Goehler J, Koo S. Safety and tolerability study of sotrovimab (VIR-7831) prophylaxis against COVID-19 infection in immunocompromised individuals with impaired SARS-CoV-2 humoral immunity. Pilot Feasibility Stud. 2023 Jun 16;9(1):100. doi: 10.1186/s40814-023-01325-y.

Reference Type: DERIVED

PMID: 37328890 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

21-755

Identifier Type: -

Identifier Source: org_study_id