Trial Outcomes & Findings for A Safety and Tolerability Study of Sotrovimab (VIR-7831) Prophylaxis Against COVID-19 in Immunocompromised Individuals (NCT NCT05210101)

Last Updated: 2024-08-15

Results Overview

Proportion of patients with treatment-emergent adverse events, serious adverse events, and adverse events of specific interest (including infusion-related and hypersensitivity reactions, anti-drug antibody (ADA) levels, and antibody-dependent enhancement

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

93 participants

Primary outcome timeframe

36 weeks after the second dose of sotrovimab

Results posted on

2024-08-15

Participant Flow

There were no significant events in the study occurring after enrollment and prior to assignment into a group - this was a single arm safety and tolerability study.

Participant milestones

Participant milestones
Measure	Sotrovimab Two intravenous (IV) doses of sotrovimab were 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.
Overall Study STARTED	93
Overall Study COMPLETED	88
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sotrovimab n=93 Participants Two intravenous (IV) doses of sotrovimab were 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.
Age, Continuous	66.4 years n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants
Sex: Female, Male Male	48 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	85 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	85 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Region of Enrollment United States	93 participants n=5 Participants

PRIMARY outcome

Timeframe: 36 weeks after the second dose of sotrovimab

Population: immunocompromised patients with impaired humoral immunity to SARS-CoV-2

Outcome measures

Outcome measures
Measure	Sotrovimab n=93 Participants 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.
Proportion of Patients With Treatment-emergent Adverse Events, Serious Adverse Events, and Adverse Events of Specific Interest Proportion of subjects with treatment-emergent grade 3-4 adverse events, per DAIDS grading criteria.	28 Participants
Proportion of Patients With Treatment-emergent Adverse Events, Serious Adverse Events, and Adverse Events of Specific Interest Proportion of subjects with antibody-dependent enhancement (ADE)	0 Participants
Proportion of Patients With Treatment-emergent Adverse Events, Serious Adverse Events, and Adverse Events of Specific Interest Proportion of study subjects with treatment-emergent serious adverse events (SAE).	27 Participants
Proportion of Patients With Treatment-emergent Adverse Events, Serious Adverse Events, and Adverse Events of Specific Interest Proportion of study subjects with infusion-related and hypersensitivity reactions	3 Participants
Proportion of Patients With Treatment-emergent Adverse Events, Serious Adverse Events, and Adverse Events of Specific Interest Proportion of study subjects with the development of antidrug antibody (ADA) levels	3 Participants

PRIMARY outcome

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

Population: immunocompromised patients with impaired humoral immunity against SARS-CoV-2, range reported is a 5-95th percentile

Evaluation of half-life of sotrovimab in immunocompromised patients with impaired humoral immunity against SARS-CoV-2.

Outcome measures

Outcome measures
Measure	Sotrovimab n=93 Participants 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.
Half-life of Sotrovimab in Immunocompromised Patients With Impaired Humoral Immunity Against SARS-CoV-2.	67.7 days (half-life) Interval 47.3 to 95.8

SECONDARY outcome

Timeframe: 36 weeks after the second dose of sotrovimab

Population: immunocompromised patients with an impaired humoral immune response to SARS-CoV-2

The proportion of study subjects who: (a) develop COVID-19 (of any severity), (b) severe COVID-19, (c) Emergency department (ED) visits, inpatient hospitalization, or ICU hospitalizations within 28 days of a new diagnosis of SARS-CoV-2, (d) need for new or increasing supplemental oxygen or mechanical ventilation within 28 days of a new diagnosis of SARS-CoV-2, and (e) death due to any cause during the study follow-up period.

Outcome measures

Outcome measures
Measure	Sotrovimab n=93 Participants 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.
COVID-19-related Outcomes Patients who developed COVID-19 (of any severity)	35 Participants
COVID-19-related Outcomes Patients who developed severe COVID-19	1 Participants

SECONDARY outcome

Timeframe: At treatment day 1, at treatment day 2

Population: immunocompromised patients with impaired humoral immunity to SARS-CoV-2

Health-related quality of life was assessed using the 36-Item Short Form Survey (SF-36), specifically focusing on the General Health domain. Each question in this domain was scored as follows: For questions 33 and 35, responses were scaled: 1 = 0, 2 = 25, 3 = 50, 4 = 75, and 5 = 100. For questions 1, 34, and 36, responses were scaled: 1 = 100, 2 = 75, 3 = 50, 4 = 25, and 5 = 0. The scores for these five questions were summed to create a composite General Health score, with possible total scores ranging from 0 (indicating the best perceived general health) to 500 (indicating the worst perceived general health). Lower scores indicate better perceived general health. We calculated the mean General Health score at two time points: treatment day 1 and treatment day 2. The reported results reflect the difference between these mean scores, with negative differences indicating improvement and positive differences indicating a decline in p

Outcome measures

Outcome measures
Measure	Sotrovimab n=93 Participants 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.
General Health Quality of Life Measurement	-0.60 scores on a scale Standard Deviation 3.27

SECONDARY outcome

Timeframe: from covid day 1 to end of hospitalization or covid day 14

Population: study subjects who acquired SARS-CoV-2 during the study period

National Institute of Allergy and Infectious Disease Ordinal Scale (NIAD-OS) was assessed at the end of hospitalization or 14 days after the diagnosis of COVID-19. The worst reported scale value was used in the analysis to adequately represent the greatest extent of their COVID-19 infection. NIAID-OS Scale Value Description 1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities or/or requiring home oxygen 3. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care 4. Hospitalized, not requiring supplemental oxygen 5. Hospitalized, requiring supplemental oxygen 6. Hospitalized, on non-invasive ventilation or high flow oxygen devices 7. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 8. Death

Outcome measures

Outcome measures
Measure	Sotrovimab n=35 Participants 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.
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)	1 units on a scale Interval 1.0 to 5.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 36 weeks after the second dose of sotrovimab

Population: immunocompromised patients with impaired humoral immunity to SARS-CoV-2

Assessment of rates of new cellular or antibody-mediated rejection events in solid organ transplant (SOT) recipients exposed to sotrovimab.

Outcome measures

Outcome measures
Measure	Sotrovimab n=93 Participants 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.
Number of Participants With New Cellular or Antibody-mediated Rejection Events	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 36 weeks after the second dose of sotrovimab

Population: immunocompromised patients with impaired humoral immunity to SARS-CoV-2

Assessment of rates of new-onset or worsening graft-versus-host disease in hematopoietic cell transplant (HCT) recipients exposed to sotrovimab.

Outcome measures

Outcome measures
Measure	Sotrovimab n=93 Participants 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.
New-onset or Worsening Graft-versus-host Disease in Hematopoietic Cell Transplant Recipients	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 36 weeks after the second dose of sotrovimab

Population: immunocompromised patients with impaired humoral immunity to SARS-CoV-2

Assessment of rates of new-onset allograft or stem cell failure requiring retransplantation in HCT recipients exposed to sotrovimab.

Outcome measures

Outcome measures
Measure	Sotrovimab n=93 Participants 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.
New-onset Allograft or Stem Cell Failure Requiring Retransplantation in HCT Recipients	0 Participants

Adverse Events

Sotrovimab

Serious events: 27 serious events

Other events: 10 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Sotrovimab n=93 participants at risk 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. 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, which became the dominant variant in between the administration of the two doses.
Blood and lymphatic system disorders Febrile Neutropenia	1.1% 1/93 • 68-74 weeks Study subjects were assessed according to the study calendar in the protocol: regular laboratory testing, scheduled investigator assessments, and scheduled questionnaires.
Cardiac disorders Heart Failure	2.2% 2/93 • 68-74 weeks Study subjects were assessed according to the study calendar in the protocol: regular laboratory testing, scheduled investigator assessments, and scheduled questionnaires.
Cardiac disorders Non-St Elevation Myocardial Infarction	1.1% 1/93 • 68-74 weeks Study subjects were assessed according to the study calendar in the protocol: regular laboratory testing, scheduled investigator assessments, and scheduled questionnaires.
Gastrointestinal disorders Colitis	1.1% 1/93 • 68-74 weeks Study subjects were assessed according to the study calendar in the protocol: regular laboratory testing, scheduled investigator assessments, and scheduled questionnaires.
Gastrointestinal disorders Pancreatitis	1.1% 1/93 • 68-74 weeks Study subjects were assessed according to the study calendar in the protocol: regular laboratory testing, scheduled investigator assessments, and scheduled questionnaires.
Gastrointestinal disorders Upper GI Bleed	1.1% 1/93 • 68-74 weeks Study subjects were assessed according to the study calendar in the protocol: regular laboratory testing, scheduled investigator assessments, and scheduled questionnaires.
General disorders Chest Pain	1.1% 1/93 • 68-74 weeks Study subjects were assessed according to the study calendar in the protocol: regular laboratory testing, scheduled investigator assessments, and scheduled questionnaires.
General disorders Non-Cardiac Chest Pain	1.1% 1/93 • 68-74 weeks Study subjects were assessed according to the study calendar in the protocol: regular laboratory testing, scheduled investigator assessments, and scheduled questionnaires.
Infections and infestations Empyema	1.1% 1/93 • 68-74 weeks Study subjects were assessed according to the study calendar in the protocol: regular laboratory testing, scheduled investigator assessments, and scheduled questionnaires.
Infections and infestations COVID-19 infection	1.1% 1/93 • 68-74 weeks Study subjects were assessed according to the study calendar in the protocol: regular laboratory testing, scheduled investigator assessments, and scheduled questionnaires.
Infections and infestations Pneumonia	5.4% 5/93 • 68-74 weeks Study subjects were assessed according to the study calendar in the protocol: regular laboratory testing, scheduled investigator assessments, and scheduled questionnaires.
Infections and infestations Tracheobronchitis	1.1% 1/93 • 68-74 weeks Study subjects were assessed according to the study calendar in the protocol: regular laboratory testing, scheduled investigator assessments, and scheduled questionnaires.
Infections and infestations Urinary Tract Infection	1.1% 1/93 • 68-74 weeks Study subjects were assessed according to the study calendar in the protocol: regular laboratory testing, scheduled investigator assessments, and scheduled questionnaires.
Infections and infestations Viral Infection	1.1% 1/93 • 68-74 weeks Study subjects were assessed according to the study calendar in the protocol: regular laboratory testing, scheduled investigator assessments, and scheduled questionnaires.
Infections and infestations Worsening Pneumonia	1.1% 1/93 • 68-74 weeks Study subjects were assessed according to the study calendar in the protocol: regular laboratory testing, scheduled investigator assessments, and scheduled questionnaires.
Infections and infestations Wound Infection	1.1% 1/93 • 68-74 weeks Study subjects were assessed according to the study calendar in the protocol: regular laboratory testing, scheduled investigator assessments, and scheduled questionnaires.
Injury, poisoning and procedural complications Burn Scar In The Bronchus	1.1% 1/93 • 68-74 weeks Study subjects were assessed according to the study calendar in the protocol: regular laboratory testing, scheduled investigator assessments, and scheduled questionnaires.
Metabolism and nutrition disorders Dehydration	1.1% 1/93 • 68-74 weeks Study subjects were assessed according to the study calendar in the protocol: regular laboratory testing, scheduled investigator assessments, and scheduled questionnaires.
Renal and urinary disorders Hematuria	1.1% 1/93 • 68-74 weeks Study subjects were assessed according to the study calendar in the protocol: regular laboratory testing, scheduled investigator assessments, and scheduled questionnaires.
Respiratory, thoracic and mediastinal disorders Bronchial Obstruction	1.1% 1/93 • 68-74 weeks Study subjects were assessed according to the study calendar in the protocol: regular laboratory testing, scheduled investigator assessments, and scheduled questionnaires.
Respiratory, thoracic and mediastinal disorders Hemoptysis	1.1% 1/93 • 68-74 weeks Study subjects were assessed according to the study calendar in the protocol: regular laboratory testing, scheduled investigator assessments, and scheduled questionnaires.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	1.1% 1/93 • 68-74 weeks Study subjects were assessed according to the study calendar in the protocol: regular laboratory testing, scheduled investigator assessments, and scheduled questionnaires.

Other adverse events

Other adverse events
Measure	Sotrovimab n=93 participants at risk 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. 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, which became the dominant variant in between the administration of the two doses.
Infections and infestations Pneumonia	5.4% 5/93 • 68-74 weeks Study subjects were assessed according to the study calendar in the protocol: regular laboratory testing, scheduled investigator assessments, and scheduled questionnaires.
Injury, poisoning and procedural complications Infusion related reaction	5.4% 5/93 • 68-74 weeks Study subjects were assessed according to the study calendar in the protocol: regular laboratory testing, scheduled investigator assessments, and scheduled questionnaires.

Additional Information

Sophia Koo, MD

Brigham and Women's Hospital

Phone: 6175258418

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60