A Study to Investigate the PK, Safety, and Tolerability of Sotrovimab vs Placebo Administered IV or IM in Japanese and Caucasian Participants

Study Overview
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Brief Summary
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This is a Phase I single-dose study to investigate the pharmacokinetics, safety, and tolerability of sotrovimab vs placebo by intravenous or intramuscular administration in healthy Japanese and Caucasian participants.

Detailed Description
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The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of a single fixed dose of sotrovimab administered intravenously (IV) or via intramuscular (IM) injection in Japanese and Caucasian healthy volunteers. This study will occur in two parts (Part 1 and Part 2). Part 1: Healthy Japanese and Caucasian participants will be randomized in a 4:1 ratio to receive a single IV infusion of sotrovimab or volume-matched saline placebo on Day 1. Participants will be blinded to study intervention. Safety, tolerability, immunogenicity, and PK of IV sotrovimab will be evaluated. Part 2: Healthy Japanese and Caucasian participants will be randomized in a 4:1 ratio to receive a single IM dose of sotrovimab or volume-matched saline placebo on Day 1. Participants will be blinded to study intervention. Safety, tolerability, immunogenicity, and PK of IM sotrovimab will be evaluated. The data from this study will be used to supplement data available from other clinical trials that were conducted in non-Japanese participants.

Official Title
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A Phase I, Single-blind, Randomized, Single-dose Clinical Pharmacology Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Sotrovimab vs Placebo by Intravenous or Intramuscular Administration in Healthy Japanese and Caucasian Participants

Conditions
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Covid19

Intervention / Treatment
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* Biological: sotrovimab
* Other: Placebo to Biologic
* Biological: sotrovimab
* Other: Placebo to Biologic


Participation Criteria
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Eligibility Criteria
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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. Japanese participants must be of Japanese ancestry, defined as having been born in Japan, being descendants of four ethnic Japanese grandparents and two ethnic Japanese parents, holding a Japanese passport or identity papers, and being able to speak Japanese. Participants should have lived outside Japan for fewer than 10 years at the time of Screening. Caucasian participants must be of Caucasian ancestry, defined as Caucasian descent as evidenced by appearance and verbal confirmation of familial heritage. Body mass index (BMI) within the range of 18 to 29.9 kg/m2 (inclusive). Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form and protocol. 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; constituting a risk when taking the study intervention or interfering with the interpretation of data. 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. Significant allergies to humanized monoclonal antibodies. Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A (IgA) dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis). 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 prescription medications (besides contraceptive medications or devices) within the 28 days prior to dosing or concomitantly, unless permitted by the protocol or approved by the Investigator in conjunction with the GSK medical monitor. Treatment with biologic agents (such as monoclonal antibodies including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing. Receipt of convalescent plasma from a recovered COVID-19 patient or anti-SARSCoV- 2 mAb within the last 3 months. Receipt of any vaccine within 48 hours prior to enrollment. Vaccination will not be allowed for 90 days after dosing. Participant has received a SARS-CoV-2 vaccine but has not completed all doses in the series more than 28 days prior to Screening Participation in the study would result in loss of blood or blood products in excess of 500 mL within a 56 day period. Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day. Enrollment in any investigational vaccine study within the last 180 days or any other investigational drug study within 30 days prior to Day 1 or within 5 half-lives of the investigational compound, whichever is longer. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 prior to dosing. Positive pre-study drug/alcohol screen. Positive HIV antibody test. History of regular alcohol consumption within 6 months prior to the study defined as: An average weekly intake of >14 units. One unit is equivalent to 8 g of alcohol: a half pint ( 240 mL) of beer, 1 glass (125 mL) of wine, or 1 (25 mL) measure of spirits. Regular use of known drugs of abuse.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 Sotrovimab intravenous infusion, single dose<br> | Biological: sotrovimab<br>* sotrovimab IV infusion, single dose<br>|
| Placebo Comparator: Part 1 Volume-matched placebo, intravenous infusion<br> | Other: Placebo to Biologic<br>* Sterile 0.9% (w/v) sodium chloride solution<br>|
| Experimental: Part 2 Sotrovimab intramuscular injection, single dose<br> | Biological: sotrovimab<br>* Sotrovimab IM injection, single dose<br>|
| Placebo Comparator: Part 2 Volume-matched placebo, intramuscular injection<br> | Other: Placebo to Biologic<br>* Sterile 0.9% (w/v) sodium chloride solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed serum concentration (Cmax) in Part 1 participants |  | Day 1 through Day 29 | 
| Maximum observed serum concentration (Cmax) in Part 2 participants |  | Day 1 through Day 29 | 
| Area under the serum-concentration time curve from Day 1 to Day 29 (AUCD1-29) in Part 1 participants |  | Day 1 through Day 29 | 
| Area under the serum-concentration time curve from Day 1 to Day 29 (AUCD1-29) in Part 2 participants |  | Day 1 through Day 29 | 
| Time to Cmax (Tmax) in Part 1 participants |  | Day 1 through Day 29 | 
| Time to Cmax (Tmax) in Part 2 participants |  | Day 1 through Day 29 | 
| Concentration at Day 29 (CD29) in Part 1 participants |  | through Day 29 | 
| Concentration at Day 29 (CD29) in Part 2 participants |  | through Day 29 | 
| Occurrence of adverse events (AEs) in Part 1 participants |  | Through Day 29 | 
| Occurrence of adverse events (AEs) in Part 2 participants |  | Through Day 29 | 
| Occurrence of serious adverse events (SAEs) in Part 1 participants |  | Through Day 29 | 
| Occurrence of serious adverse events (SAEs) in Part 2 participants |  | Through Day 29 | 
| Occurrence of adverse events of special interest (AESIs) in Part 1 participants |  | Through Day 29 | 
| Occurrence of adverse events of special interest (AESIs) in Part 2 participants |  | Through Day 29 | 
| Occurrence of clinically significant abnormalities on 12-lead electrocardiogram (ECG) readings in Part 1 participants |  | Through Day 29 | 
| Occurrence of clinically significant abnormalities on 12-lead electrocardiogram (ECG) readings in Part 2 participants |  | Through Day 29 | 
| Occurrence of clinically significant changes in vital signs compared to Baseline in Part 2 participants |  | Baseline and up toDay 29 | 
| Occurrence of clinically significant laboratory abnormalities in Part 1 participants |  | Through Day 29 | 
| Occurrence of clinically significant laboratory abnormalities in Part 2 participants |  | Through Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax in Part 1 participants |  | Day 1 through 18 weeks | 
| Cmax in Part 2 participants |  | Day 1 through 18 weeks | 
| Area under the serum concentration-time curve extrapolated to infinite time (AUCinf) in Part 1 participants |  | Day 1 through 18 weeks | 
| Area under the serum concentration-time curve extrapolated to infinite time (AUCinf) in Part 2 participants |  | Day 1 through 18 weeks | 
| Area under the curve from the time of dosing to the time of the last measurable (positive) concentration (AUClast) in Part 1 participants |  | Day 1 through 18 weeks | 
| Area under the curve from the time of dosing to the time of the last measurable (positive) concentration (AUClast) in Part 2 participants |  | Day 1 through 18 weeks | 
| Tmax in Part 1 participants |  | Day 1 through 18 weeks | 
| Tmax in Part 2 participants |  | Day 1 through 18 weeks | 
| Time of the last quantifiable concentration (Tlast) in Part 1 participants |  | Day 1 through 18 weeks | 
| Time of the last quantifiable concentration (Tlast) in Part 2 participants |  | Day 1 through 18 weeks | 
| Terminal elimination half-life (t1/2) of sotrovimab in Part 1 participants |  | Day 1 through 18 weeks | 
| Terminal elimination half-life (t1/2) of sotrovimab in Part 2 participants |  | Day 1 through 18 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2 coronavirus, coronavirus disease 2019, COVID-19, Japanese pharmacokinetics