Clinical trial NCT05210101: A Safety and Tolerability Study of Sotrovimab (VIR-7831) Prophylaxis Against COVID-19 in Immunocompromised Individuals
Official title: A Safety and Tolerability Study of Sotrovimab (VIR-7831) Prophylaxis Against COVID-19 Infection in Immunocompromised Individuals With Impaired SARS-CoV-2 Humoral Immunity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: SARS CoV 2 Infection
Keywords: Prophylaxis
Immunocompromised host
Transplant
Monoclonal antibodies
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Massachusetts General Hospital
name: Dana-Farber Cancer Institute
name: GlaxoSmithKline
First posted: 2022-01-27
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Proportion of Patients With Treatment-emergent Adverse Events, Serious Adverse Events, and Adverse Events of Specific Interest
timeFrame: 36 weeks after the second dose of sotrovimab
measure: Half-life of Sotrovimab in Immunocompromised Patients With Impaired Humoral Immunity Against SARS-CoV-2.
timeFrame: Within 1 hour of the first dose infusion of sotrovimab and on day 11, 29, and 59. Prior to the second dose, within 1 hour of the second dose infusion of sotrovimab, and 11, 29, 59, and 168 days after
Secondary outcomes:
measure: COVID-19-related Outcomes
timeFrame: 36 weeks after the second dose of sotrovimab
measure: General Health Quality of Life Measurement
timeFrame: At treatment day 1, at treatment day 2
measure: In Patients Who Develop COVID-19, the Greatest Extent of COVID-19 Symptoms, as Assessed Using the 8-point National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS)
timeFrame: from covid day 1 to end of hospitalization or covid day 14
Other outcomes:
measure: Number of Participants With New Cellular or Antibody-mediated Rejection Events
timeFrame: 36 weeks after the second dose of sotrovimab
measure: New-onset or Worsening Graft-versus-host Disease in Hematopoietic Cell Transplant Recipients
timeFrame: 36 weeks after the second dose of sotrovimab
measure: New-onset Allograft or Stem Cell Failure Requiring Retransplantation in HCT Recipients
timeFrame: 36 weeks after the second dose of sotrovimab
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber/Brigham and Women's Cancer Center
name: Sophia Koo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brigham and Women's Hospital
name: Jennifer Manne-Goehler, MD, ScD
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: Sarah P Hammond, MD
role: PRINCIPAL_INVESTIGATOR
References: