Relative Bioavailability, Safety, and Tolerability of Single-dose Sotrovimab Injection in Adults (COSMIC)

NCT05280717 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: VIR-7831-5012GSK Study 218128
• Study Type: interventional
• Target: 316
• Locations: 1 country
• Sites: 10

Brief Summary

This clinical pharmacology study will evaluate the relative bioavailability, safety, and tolerability of two different concentrations of sotrovimab injections administered at different injection sites in male or female healthy participants aged 18 to 65 years. The study will be conducted in three parts (Part A, an optional Part B and Part C). Part B and Part C (cohort 2) were optional so they were not initiated. Part C cohort 1 was discontinued early in the context of evolving variants with increased fold changes in the in vitro half maximal inhibitory concentration (IC50) and uncertainty in the clinical relevance of these changes.

Conditions

Covid19

Keywords

COVID-19; Pharmacokinetics; Safety; Sotrovimab; Relative bioavailability; Healthy participants

Outcome Measures

Primary Outcomes (4)

• Part A (Treatment Arms 1 and 2): Area Under the Serum Concentration-time Curve (AUC) From Day 1 to Day 29 (AUC[D1 to 29]) Following Administration of Sotrovimab

  Blood samples were collected at indicated time points for pharmacokinetic analysis of sotrovimab. Pharmacokinetic (PK) parameters were calculated using standard non-compartmental analysis.

  Day 1: Pre-dose, 1, 2, 6 and 8 hours post-dose; Days 2, 3, 5, 8, 15 and 29 post-dose

• Part A (Treatment Arms 1 and 2): Maximum Observed Concentration (Cmax) Following Administration of Sotrovimab

  Blood samples were collected at indicated time points for pharmacokinetic analysis of sotrovimab. PK parameters were calculated using standard non-compartmental analysis.

  Day 1: Pre-dose, 1, 2, 6 and 8 hours post-dose; Days 2, 3, 5, 8, 15 and 29 post-dose

• Part A (Treatment Arms 1 and 2): Number of Participants With Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESI) and Common (>=5%) Non-serious Adverse Events (Non-SAEs) Through Day 29

  An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life- threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, significant medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed before. Adverse events which were not Serious were considered as non-serious adverse events. Number of participants who had common (\>=5%) non-SAEs and SAEs are presented. AESIs included hypersensitivity reactions and injection site reactions based on a predefined list of terms.

  Up to Day 29

• Part C (Cohorts 1 and 2): Number of Participants With SAEs, AESIs and Common (>=5%) Non-SAEs Through Day 29

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, significant medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed before. Adverse events which were not Serious were considered as non-serious adverse events. Number of participants who had common (\>=5%) non-SAEs and SAEs are presented. AESI included hypersensitivity reaction based on a predefined list of terms.

  Up to Day 29

Secondary Outcomes (14)

• Part A (Treatment Arms 1, 3 and 4): AUC(D1 to 29) Following Administration of Sotrovimab

  Day 1: Pre-dose, 1, 2, 6 and 8 hours post-dose; Days 2, 3, 5, 8, 15 and 29 post-dose

• Part A (Treatment Arms 1, 3 and 4): Cmax Following Administration of Sotrovimab

  Day 1: Pre-dose, 1, 2, 6 and 8 hours post-dose; Days 2, 3, 5, 8, 15 and 29 post-dose

• Part B: AUC(D1-29) Following Administration of Sotrovimab

  Day 1: Pre-dose, 1, 2, 6 and 8 hours post-dose; Days 2, 3, 5, 8, 15 and 29 post-dose

• Part B: Cmax Following Administration of Sotrovimab

  Day 1: Pre-dose, 1, 2, 6 and 8 hours post-dose; Days 2, 3, 5, 8, 15 and 29 post-dose

• Part C (Cohorts 1 and 2): AUC(D1-29) Following Administration of Sotrovimab

  Day 1: Pre-dose, end of infusion, 1, 2, 6 and 8 hours post-dose; Days 2, 3, 5, 8, 15 and 29 post-dose

Study Arms (7)

Part A: Treatment arm 1- Sotrovimab 62.5 mg/mL (Dorsogluteal)

EXPERIMENTAL

Participants will receive a single 500 milligram (mg) of 62.5 milligram per milliliter (mg/mL) sotrovimab administered via two injections intramuscularly into the dorsogluteal muscle on Day 1.

Biological: sotrovimab

Part A: Treatment arm 2- Sotrovimab 100 mg/mL (Dorsogluteal)

EXPERIMENTAL

Participants will receive a single 500 mg of 100 mg/mL sotrovimab administered intramuscularly into the dorsogluteal muscle on Day 1.

Biological: sotrovimab

Part A: Treatment arm 3- Sotrovimab 100 mg/mL (Anterolateral Thigh)

EXPERIMENTAL

Participants will receive a single 500 mg of 100 mg/mL sotrovimab administered intramuscularly into the anterolateral thigh muscles on Day 1.

Biological: sotrovimab

Part A: Treatment arm 4- Sotrovimab 100 mg/mL (Deltoid)

EXPERIMENTAL

Participants will receive a single 500 mg of 100 mg/mL sotrovimab administered two injections intramuscularly into the deltoid muscles on Day 1.

Biological: sotrovimab

Part B: Sotrovimab

EXPERIMENTAL

Participants will receive 500 mg of 100 mg/mL and/or 62.5 mg/mL sotrovimab on Day 1.

Biological: sotrovimab

Part C: Cohort 1-Sotrovimab

EXPERIMENTAL

Participants will receive a single 3000 mg of sotrovimab intravenous (IV) infusion over 60 minutes on Day 1.

Biological: sotrovimab

Part C: Cohort 2-Sotrovimab

EXPERIMENTAL

Participants are planned to receive up to 3000 mg of sotrovimab intravenously on Day 1.

Biological: sotrovimab

Interventions

sotrovimab BIOLOGICAL

via IM injection

Part A: Treatment arm 1- Sotrovimab 62.5 mg/mL (Dorsogluteal)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants, aged 18 to 65 years, inclusive.
• Participants who are healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
• Body Mass Index (BMI) within the range of 18 to 30 kilogram per square meter (kg/m\^2).
• Capable of giving signed informed consent

You may not qualify if:

• History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs
• Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years
• Breast cancer within the past 10 years
• Abnormal blood pressure at Screening.
• Known hypersensitivity to any constituent present in the investigational product or history of severe hypersensitivity or anaphylaxis after receiving a COVID-19 vaccine
• Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions
• Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Use of any over the counter or prescription medications unless permitted by the protocol or approved by the Investigator in conjunction with the GSK medical monitor.
• For Part A and Part B, any condition that would prohibit receipt of injections in the investigator's opinion, such as coagulation disorder, bleeding diathesis, or thrombocytopenia.
• Treatment with biologic agents (such as) within 3 months or 5 half-lives
• Receipt of convalescent plasma from a recovered COVID-19 participant or anti- severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) monoclonal antibody (mAb) within the last 3 months.
• Receipt of any vaccine within 48 hours prior to enrollment.
• Has received a SARS-CoV-2 vaccine but has not completed all doses in the series more than 28 days prior to Screening.
• Exposure to more than 4 new chemical entities (e.g., investigational pharmaceuticals) within 12 months prior to the first dosing day.
• Enrolment in any investigational vaccine study within the last 180 days or enrollment in any other investigational drug study within 30 days prior to Day 1 or within 5 half-lives

Sponsors & Collaborators

• Vir Biotechnology, Inc.: lead
• GlaxoSmithKline: collaborator

Study Sites (10)

Investigative Site

Riverside, California, 92503, United States

Location

Investigative Site

Atlantis, Florida, 33462, United States

Location

Investigative Site

Edgewater, Florida, 32132, United States

Location

Investigative Site

St Louis, Missouri, 63141, United States

Location

Investigative Site

Binghamton, New York, 13901, United States

Location

Investigative Site

Yukon, Oklahoma, 73099, United States

Location

Investigative Site

Medford, Oregon, 97504, United States

Location

Investigative Site

Austin, Texas, 78745, United States

Location

Investigative Site

Houston, Texas, 77065, United States

Location

Investigative Site

West Jordan, Utah, 84088, United States

Location

Related Publications (2)

• Sanchez-Pearson Y, Moore J, Daniluk J, Bhangu S, Parra S, El Zailik A, Sarkar P, Aylott A, Moyo F, Peppercorn A, Skingsley A. Safety, Tolerability and Pharmacokinetics of a High-Dose, Rapid-Infusion Monoclonal Antibody: Phase I Results for Intravenous Sotrovimab 3000 mg. Drugs R D. 2025 Dec;25(4):367-376. doi: 10.1007/s40268-025-00530-9. Epub 2025 Dec 1.

  PMID: 41324898 DERIVED

• Moore J, Aylott A, Chen WH, Daniluk J, Hawes IA, Parra S, Sarkar P, Sanchez-Pearson Y, Turner M, Peppercorn A, Skingsley A. Safety and tolerability of intramuscular sotrovimab administered at different injection sites: results from the Phase 1 COSMIC study. MAbs. 2025 Dec;17(1):2456467. doi: 10.1080/19420862.2025.2456467. Epub 2025 Jan 29.

  PMID: 39881564 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

sotrovimab

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Study Inquiry
• Organization: Vir Biotechnology, Inc.

clinicaltrials@vir.bio

415-654-5281

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2022
• First Posted: March 15, 2022
• Study Start: March 28, 2022
• Primary Completion: April 5, 2023
• Study Completion: November 6, 2023
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-04

Locations

US (10)