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

NCT05280717
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Phase
Phase 1
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Recruitment status
Terminated
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Participants
316
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Lead sponsor
Vir Biotechnology, Inc.
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Start date
2022-03-28
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Number of sites
10
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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.
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Acronym
COSMIC
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Short title
Relative Bioavailability, Safety, and Tolerability of Single-dose Sotrovimab Injection in Adults (COSMIC)
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Official title
A Phase 1, Open-label, Randomized, Parallel Group, Single-dose Clinical Pharmacology Study to Investigate the Relative Bioavailability, Safety, and Tolerability of Two Different Concentrations of Sotrovimab Administered at Different Injection Sites, in Male or Female Healthy Participants Aged 18 to 65 Years
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Control arm
Open label
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Registry reports results
Yes
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Listing at source
Listed
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Recruitment status
Terminated
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Phase
Phase 1
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Study type
Interventional
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Reason stopped
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.
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Completion date
2023-11-06
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First posted
2022-03-15
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Registry last updated
2024-09-19
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Primary completion date
2023-04-05
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Start date
2022-03-28
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Actual participants
316
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Participants
316
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Participant count basis
Actual
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Protocol amendments
2
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Number of sites
10
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Vir Biotechnology, Inc.
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05280717
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ClinicalTrials.gov ID
NCT05280717
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Sources for study design
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  1. 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

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

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

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

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

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

  3. 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

    Timeframe: Up to 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.

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

    Timeframe: Up to 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.

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

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

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

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

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

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

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

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

    Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of sotrovimab.

  4. Part B: Cmax Following Administration of Sotrovimab

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

    Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of sotrovimab.

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

    Timeframe: 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

    Blood samples were collected at indicated time points for pharmacokinetic analysis of sotrovimab in Cohort 1. PK parameters were calculated using standard non-compartmental analysis.

  6. Part C (Cohorts 1 and 2): Cmax Following Administration of Sotrovimab

    Timeframe: 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

    Blood samples were collected at indicated time points for pharmacokinetic analysis of sotrovimab in Cohort 1. PK parameters were calculated using standard non-compartmental analysis.

  7. Part A (Treatment Arms 1, 2, 3 and 4): Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUCinf) Following Administration of Sotrovimab at 3 Injection Sites

    Timeframe: Day 1: Pre-dose, 1, 2, 6 and 8 hours post-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 140, 168 (Week 24) post-dose

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

  8. Part B: AUCinf Following Administration of Sotrovimab at up to 2 Injection Sites

    Timeframe: Day 1: Pre-dose, 1, 2, 6 and 8 hours post-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 140, 168 (Week 24) post-dose

    Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of sotrovimab.

  9. Part A (Treatment Arms 1, 2, 3 and 4): Serum Concentration Following Administration of Sotrovimab

    Timeframe: Day 1: Pre-dose, 1, 2, 6 and 8 hours post-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 140, 168 post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of sotrovimab.

  10. Part B: Serum Concentration Following Administration of Sotrovimab

    Timeframe: Day 1: Pre-dose, 1, 2, 6 and 8 hours post-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 140, 168 post-dose

    Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of sotrovimab.

  11. Part C: Serum Concentration Following Administration of Sotrovimab

    Timeframe: Day 1: Pre-dose, end of infusion, 1, 2, 6 and 8 hours post-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 140, 168 post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of sotrovimab in Cohort 1.

  12. Part A (Treatment Arms 1, 2, 3 and 4): Number of Participants With SAEs, AESI and Common (>=5%) Non-SAEs Through Day 29 and Week 35

    Timeframe: Up to Day 29 and Up to Week 35

    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. AESIs included hypersensitivity reactions and injection site reactions based on a predefined list of terms.

  13. Part B: Number of Participants With SAEs, AESIs and Common (>=5%) Non-SAEs Through Day 29 and Week 35

    Timeframe: Up to Day 29 and Up to Week 35

    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. AESIs included hypersensitivity reactions and injection site reactions based on a predefined list of terms.

  14. Part C: Number of Participants With SAEs, AESIs and Common (>=5%) Non-SAEs Through Week 35

    Timeframe: Up to Week 35

    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. AESIs included hypersensitivity reactions and injection site reactions based on a predefined list of terms.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Maximum age
65 Years
Healthy volunteers
Yes

  • 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.
  • For Part C, inclusion in the Japanese subgroup analysis, a participant must meet all of the following criteria: Japanese ancestry, defined as being a descendant of 4 ethnic Japanese grandparents and 2 ethnic Japanese parents.
  • Body Mass Index (BMI) within the range of 18 to 30 kilogram per square meter (kg/m^2).
  • Capable of giving signed informed consent

  • 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
  • Current enrolment or past participation in this clinical study.
  • A positive pre-study hepatitis B surface antigen or positive hepatitis C antibody test result at Screening or within 3 months prior to dosing.
  • Positive pre-study drug/alcohol screen.
  • Positive human immunodeficiency virus (HIV) antibody test.
  • History of regular alcohol consumption within 6 months prior to the study.
  • Regular use of known drugs of abuse.
  • Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
Sources for eligibility
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  • Investigative SiteRiverside, United States
  • Investigative SiteAtlantis, United States
  • Investigative SiteEdgewater, United States
  • Investigative SiteSt Louis, United States
  • Investigative SiteBinghamton, United States
  • Investigative SiteYukon, United States
  • Investigative SiteMedford, United States
  • Investigative SiteAustin, United States
  • Investigative SiteHouston, United States
  • Investigative SiteWest Jordan, United States
Sources for sites
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Sources for references
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Related records

Drugs (1)

Collaborators (1)

Lead sponsors (1)

Conditions (1)