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

Study Overview
=================
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).

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

Conditions
-----------------
Covid19

Intervention / Treatment
-----------------
* Biological: sotrovimab
* Biological: sotrovimab
* Biological: sotrovimab
* Biological: sotrovimab
* Biological: sotrovimab
* Biological: sotrovimab
* Biological: sotrovimab


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A Cohort 1: Concentration 1 of sotrovimab<br>administered at injection site 1 | Biological: sotrovimab<br>* via IM injection<br>|
| Experimental: Part A Cohort 2: Concentration 2 of sotrovimab<br>administered at injection site 1 | Biological: sotrovimab<br>* via IM injection<br>|
| Experimental: Part A Cohort 3: Concentration 2 of sotrovimab<br>administered at injection site 2 | Biological: sotrovimab<br>* via IM injection<br>|
| Experimental: Part A Cohort 4: Concentration 2 of sotrovimab<br>administered at injection site 3 | Biological: sotrovimab<br>* via IM injection<br>|
| Experimental: Part B Cohort 5: Concentration 1 of sotrovimab<br>administered at potential injection site 1,2,3 or other | Biological: sotrovimab<br>* via IM injection<br>|
| Experimental: Part B Cohort 6: Concentration 2 of sotrovimab<br>administered at potential injection site 1,2,3 or other | Biological: sotrovimab<br>* via IM injection<br>|
| Experimental: Part C Cohort 7: Concentration 2 of sotrovimab<br>administered by intravenous (IV) infusion | Biological: sotrovimab<br>* via IV infusion<br>|
| Experimental: Part C Cohort 8: Concentration 2 of sotrovimab<br>administered by IV infusion | Biological: sotrovimab<br>* via IV infusion<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A (Cohort 1, 2): Area under the serum concentration-time curve (AUC) from Day 1 to Day 29 (AUC D1-29) following administration of sotrovimab |  | Up to Day 29 | 
| Part A (Cohort 1, 2): Maximum observed concentration (Cmax) following administration of sotrovimab through Day 29 |  | Up to Day 29 | 
| Part A (Cohort 1, 2): Number of participants with adverse events (AEs), serious adverse events (SAEs), and AEs of special interest (AESI) through Day 29 |  | Up to Day 29 | 
| Part C (Cohort 7, 8): Number of participants with AEs, SAEs, and AESI |  | Up to Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A (Cohort 1, 3, 4): AUC(D1-29) following administration of sotrovimab |  | Up to Day 29 | 
| Part A (Cohort 1, 3, 4): Cmax following administration of sotrovimab through Day 29 |  | Up to Day 29 | 
| Part A (Cohort 1, 2, 3, 4): Area under the serum concentration-time curve from time zero to infinity (AUCinf) following administration of sotrovimab at injection sites 1, 2 and 3 through Week 24 |  | Up to Week 24 | 
| Part A: Serum concentration following administration of sotrovimab through Day 29 |  | Up to Day 29 | 
| Part A: Serum concentration following administration of sotrovimab through Week 24 |  | Up to Week 24 | 
| Part A (Cohort 3, 4) and Part B: Number of participants with AEs, SAEs, and AESI |  | Up to Day 29 | 
| Part A and Part B: Number of participants with AEs, SAEs, and AESI |  | Up to Week 35 | 
| Part B: AUC(D1-29) following administration of sotrovimab |  | Up to Day 29 | 
| Part B: Cmax following administration of sotrovimab through Day 29 |  | Up to Day 29 | 
| Part B: AUCinf following administration of sotrovimab at up to 2 injection sites through Week 24 |  | Up to Week 24 | 
| Part B: Serum concentration following administration of sotrovimab through Day 29 |  | Up to Day 29 | 
| Part B: Serum concentration following administration of sotrovimab through Week 24 |  | Up to Week 24 | 
| Part C: AUC(D1-29) following administration of sotrovimab |  | Up to Day 29 | 
| Part C: Cmax following administration of sotrovimab through Day 29 |  | Up to Day 29 | 
| Part C: Serum concentration following administration of sotrovimab through Day 29 |  | Up to Day 29 | 
| Part C: Serum concentration following administration of sotrovimab through Week 24 |  | Up to Week 24 | 
| Part C: Number of participants with AEs, SAEs, and AESI |  | Up to Week 35 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COVID-19, Pharmacokinetics, Safety, Sotrovimab, Relative bioavailability, Healthy participants