Clinical trial NCT04988152: A Study to Investigate the PK, Safety, and Tolerability of Sotrovimab vs Placebo Administered IV or IM in Japanese and Caucasian Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Covid19
Keywords: SARS-CoV-2 coronavirus
coronavirus disease 2019
COVID-19
Japanese pharmacokinetics
Lead sponsor: Vir Biotechnology, Inc.
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2021-08-03
Enrollment: 48
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: OTHER

Brief summary: 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: 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.

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.
* 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.

Primary outcomes:
measure: Part 1: Maximum Observed Serum Concentration (Cmax) of Sotrovimab Through Day 29
timeFrame: Day 1: Pre-dose, at end of infusion (EOI) and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Days 8, 15 and 29
measure: Part 1: Area Under the Serum-concentration Time Curve From Day 1 to Day 29 (AUC[D1-29]) of Sotrovimab
timeFrame: Day 1: Pre-dose, at end of infusion and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Days 8, 15 and 29
measure: Part 1: Time to Cmax (Tmax) of Sotrovimab Through Day 29
timeFrame: Day 1: Pre-dose, at end of infusion and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Days 8, 15 and 29
measure: Part 1: Concentration at Day 29 (CD29) Following Administration of Sotrovimab
timeFrame: Day 1: Pre-dose, at end of infusion and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Days 8, 15 and 29
measure: Part 2: Cmax of Sotrovimab Through Day 29
timeFrame: Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Days 8, 15 and 29
measure: Part 2: AUC(D1-29) of Sotrovimab
timeFrame: Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Days 8, 15 and 29
measure: Part 2: Tmax of Sotrovimab Through Day 29
timeFrame: Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Days 8, 15 and 29
measure: Part 2: CD29 of Sotrovimab
timeFrame: Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Days 8, 15 and 29
measure: Part 1: Number of Participants With Serious Adverse Events (SAE) and Common Non-serious Adverse Events (Non-SAE) Through Day 29
timeFrame: Up to Day 29
measure: Part 1: Number of Participants With Adverse Events of Special Interest (AESI) Through Day 29
timeFrame: Up to Day 29
measure: Part 1: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings Through Day 29
timeFrame: Up to Day 29
measure: Part 1: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29
timeFrame: Baseline (Day 1) and up to Day 29
measure: Part 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29
timeFrame: Baseline (Day 1) and up to Day 29
measure: Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29
timeFrame: Baseline (Day 1) and up to Day 29
measure: Part 2: Number of Participants With SAE and Common Non-SAE Through Day 29
timeFrame: Part 2: Number of participants with SAE and common non-SAE through Day 29
measure: Part 2: Number of Participants With AESI Through Day 29
timeFrame: Up to Day 29
measure: Part 2: Number of Participants With Abnormal Clinically Significant ECG Findings Through Day 29
timeFrame: Up to Day 29
measure: Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29
timeFrame: Baseline (Day) and up to Day 29
measure: Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29
timeFrame: Baseline (Day 1) and up to Day 29
measure: Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29
timeFrame: Baseline (Day 1) and up to Day 29
Secondary outcomes:
measure: Part 1: Cmax of Sotrovimab Through Week 18
timeFrame: Day 1: Pre-dose, at end of infusion and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Weeks 2, 3, 4, 6, 8, 12 and 18
measure: Part 1: Area Under the Serum Concentration-time Curve Extrapolated to Infinite Time (AUC[0-infinity]) of Sotrovimab Through Week 18
timeFrame: Day 1: Pre-dose, at end of infusion and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Weeks 2, 3, 4, 6, 8, 12 and 18
measure: Part 1: Area Under the Curve From the Time of Dosing to the Time of the Last Measurable (Positive) Concentration (AUClast) of Sotrovimab Through Week 18
timeFrame: Day 1: Pre-dose, at end of infusion and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Weeks 2, 3, 4, 6, 8, 12 and 18
measure: Part 1: Tmax of Sotrovimab Through Week 18
timeFrame: Day 1: Pre-dose, at end of infusion and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Weeks 2, 3, 4, 6, 8, 12 and 18
measure: Part 1: Time of the Last Quantifiable Concentration (Tlast) of Sotrovimab Through Week 18
timeFrame: Day 1: Pre-dose, at end of infusion and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Weeks 2, 3, 4, 6, 8, 12 and 18
measure: Part 1: Terminal Elimination Half-life (t1/2) of Sotrovimab Through Week 18
timeFrame: Weeks 2, 3, 4, 6, 8, 12 and 18
measure: Part 2: Cmax of Sotrovimab Through Week 18
timeFrame: Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Weeks 2, 3, 4, 6, 8, 12 and 18
measure: Part 2: AUC(0-infinity) of Sotrovimab Through Week 18
timeFrame: Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Weeks 2, 3, 4, 6, 8, 12 and 18
measure: Part 2: AUClast of Sotrovimab Through Week 18
timeFrame: Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Weeks 2, 3, 4, 6, 8, 12 and 18
measure: Part 2: Tmax of Sotrovimab Through Week 18
timeFrame: Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Weeks 2, 3, 4, 6, 8, 12 and 18
measure: Part 2: Tlast of Sotrovimab Through Week 18
timeFrame: Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Weeks 2, 3, 4, 6, 8, 12 and 18
measure: Part 2: T1/2 of Sotrovimab Through Week 18
timeFrame: Weeks 2, 3, 4, 6, 8, 12 and 18
measure: Part 1: Number of Participants With SAE and Common Non-SAE Through Week 18
timeFrame: Up to Week 18
measure: Part 1: Number of Participants With AESI Through Week 18
timeFrame: Up to Week 18
measure: Part 1: Number of Participants With Abnormal Clinically Significant ECG Findings Through Week 18
timeFrame: Up to Week 18
measure: Part 1: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 18
timeFrame: Baseline (Day 1) and up to Week 18
measure: Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18
timeFrame: Baseline (Day 1) and up to Week 18
measure: Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18
timeFrame: Baseline (Day 1) and up to Week 18
measure: Part 2: Number of Participants With SAE and Common Non-SAE Through Week 18
timeFrame: Up to Week 18
measure: Part 2: Number of Participants With AESI Through Week 18
timeFrame: Up to Week 18
measure: Part 2: Number of Participants With Abnormal Clinically Significant ECG Findings Through Week 18
timeFrame: Up to Week 18
measure: Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 18
timeFrame: Baseline (Day 1) and up to Week 18
measure: Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18
timeFrame: Baseline (Day 1) and up to Week 18
measure: Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18
timeFrame: Baseline (Day 1) and up to Week 18
Other outcomes:
measure: Part 1 and Part 2: Bioavailability of Sotrovimab IM Versus IV Formulation Using AUClast
timeFrame: Part 1: Day 1 (Pre-dose, at end of infusion and 1,2,6,8,24 [Day 2] and 48 [Day 3] hours after end of infusion); Weeks 2,3,4,6,8,12,18; Part 2: Day 1(Pre-dose and 1,2,6,8,24 [Day 2] and 48 [Day 3] hours after first IM injection); Weeks 2,3,4, 6,8,12,18
Locations:
city: Anaheim
country: United States
facility: Investigative Site
state: California
city: Glendale
country: United States
facility: Investigative Site
state: California
Study officials:
References: