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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 504
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Part A: Treatment arm 1- Sotrovimab 62.5 mg/mL (Dorsogluteal)
Participants will receive a single 500 milligram (mg) of 62.5 milligram per milliliter (mg/mL) sotrovimab administered via two injections intramuscularly into the dorsogluteal muscle on Day 1.
干预措施: sotrovimab (Biological)
Part A: Treatment arm 2- Sotrovimab 100 mg/mL (Dorsogluteal)
Participants will receive a single 500 mg of 100 mg/mL sotrovimab administered intramuscularly into the dorsogluteal muscle on Day 1.
干预措施: sotrovimab (Biological)
Part A: Treatment arm 3- Sotrovimab 100 mg/mL (Anterolateral Thigh)
Participants will receive a single 500 mg of 100 mg/mL sotrovimab administered intramuscularly into the anterolateral thigh muscles on Day 1.
干预措施: sotrovimab (Biological)
Part A: Treatment arm 4- Sotrovimab 100 mg/mL (Deltoid)
Participants will receive a single 500 mg of 100 mg/mL sotrovimab administered two injections intramuscularly into the deltoid muscles on Day 1.
干预措施: sotrovimab (Biological)
Part B: Sotrovimab
Participants will receive 500 mg of 100 mg/mL and/or 62.5 mg/mL sotrovimab on Day 1.
干预措施: sotrovimab (Biological)
Part C: Cohort 1-Sotrovimab
Participants will receive a single 3000 mg of sotrovimab intravenous (IV) infusion over 60 minutes on Day 1.
干预措施: sotrovimab (Biological)
Part C: Cohort 2-Sotrovimab
Participants are planned to receive up to 3000 mg of sotrovimab intravenously on Day 1.
干预措施: sotrovimab (Biological)
结局指标
主要结局
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
时间窗: 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.
Part A (Treatment Arms 1 and 2): Maximum Observed Concentration (Cmax) Following Administration of Sotrovimab
时间窗: 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.
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
时间窗: 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.
Part C (Cohorts 1 and 2): Number of Participants With SAEs, AESIs and Common (>=5%) Non-SAEs Through Day 29
时间窗: 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.
次要结局
- Part A (Treatment Arms 1, 3 and 4): AUC(D1 to 29) Following Administration of Sotrovimab(Day 1: Pre-dose, 1, 2, 6 and 8 hours post-dose; Days 2, 3, 5, 8, 15 and 29 post-dose)
- Part A (Treatment Arms 1, 3 and 4): Cmax Following Administration of Sotrovimab(Day 1: Pre-dose, 1, 2, 6 and 8 hours post-dose; Days 2, 3, 5, 8, 15 and 29 post-dose)
- Part B: AUC(D1-29) Following Administration of Sotrovimab(Day 1: Pre-dose, 1, 2, 6 and 8 hours post-dose; Days 2, 3, 5, 8, 15 and 29 post-dose)
- Part B: Cmax Following Administration of Sotrovimab(Day 1: Pre-dose, 1, 2, 6 and 8 hours post-dose; Days 2, 3, 5, 8, 15 and 29 post-dose)
- Part C (Cohorts 1 and 2): AUC(D1-29) Following Administration of Sotrovimab(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)
- Part C (Cohorts 1 and 2): Cmax Following Administration of Sotrovimab(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)
- 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(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)
- Part B: AUCinf Following Administration of Sotrovimab at up to 2 Injection Sites(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)
- Part A (Treatment Arms 1, 2, 3 and 4): Serum Concentration Following Administration of Sotrovimab(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)
- Part B: Serum Concentration Following Administration of Sotrovimab(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)
- Part C: Serum Concentration Following Administration of Sotrovimab(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)
- 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(Up to Day 29 and Up to Week 35)
- Part B: Number of Participants With SAEs, AESIs and Common (>=5%) Non-SAEs Through Day 29 and Week 35(Up to Day 29 and Up to Week 35)
- Part C: Number of Participants With SAEs, AESIs and Common (>=5%) Non-SAEs Through Week 35(Up to Week 35)