Clinical trial NCT05280717: Relative Bioavailability, Safety, and Tolerability of Single-dose Sotrovimab Injection in Adults (COSMIC)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Covid19
Keywords: COVID-19
Pharmacokinetics
Safety
Sotrovimab
Relative bioavailability
Healthy participants
Lead sponsor: Vir Biotechnology, Inc.
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2022-03-15
Enrollment: 316
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: 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
measure: 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
measure: 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
measure: 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
Secondary outcomes:
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: Part C: Number of Participants With SAEs, AESIs and Common (>=5%) Non-SAEs Through Week 35
timeFrame: Up to Week 35
Other outcomes:
Locations:
city: Riverside
country: United States
facility: Investigative Site
state: California
city: Atlantis
country: United States
facility: Investigative Site
state: Florida
city: Edgewater
country: United States
facility: Investigative Site
state: Florida
city: Saint Louis
country: United States
facility: Investigative Site
state: Missouri
city: Binghamton
country: United States
facility: Investigative Site
state: New York
city: Yukon
country: United States
facility: Investigative Site
state: Oklahoma
city: Medford
country: United States
facility: Investigative Site
state: Oregon
city: Austin
country: United States
facility: Investigative Site
state: Texas
city: Houston
country: United States
facility: Investigative Site
state: Texas
city: West Jordan
country: United States
facility: Investigative Site
state: Utah
Study officials:
References: