A Phase 1 Double-Blind (Sponsor-unblinded), Placebo-Controlled, Randomized, Single Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of a Parenterally Administered Suspension of Investigational Capsid Inhibitors in Healthy Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 85
- 试验地点
- 2
- 主要终点
- SAD: Change from Baseline in Liver Chemistry Parameters: Alkaline Phosphatase, AST, and ALT (International Units per liter)
研究概览
简要总结
The primary purpose of the study is to investigate safety and tolerability following single and multiple ascending subcutaneous (SC) and intramuscular (IM) doses of capsid inhibitors in healthy participants. The study will also describe the pharmacokinetics following single and multiple ascending SC and IM doses of capsid inhibitors in healthy participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants who are overtly healthy.
- •Participants who are negative on a single test for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) (approved molecular polymerase chain reaction (PCR), point of care test), performed on the day of admission (Day -1). A negative result is required prior to the administration of study intervention on Day
- •Male or female participants of non-childbearing potential.
- •Capable of giving signed informed consent.
排除标准
- •History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, neurological or psychiatric 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.
- •Abnormal blood pressure.
- •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.
- •Current or chronic history of liver disease or known hepatic or biliary abnormalities.
- •History of sensitivity to any of the study interventions, a history of drug allergy or other allergy that contraindicates their participation.
- •The participant has an underlying skin disease or disorder that would interfere with assessment of injection sites.
- •Participants considered to have insufficient musculature to allow safe capsid inhibitor intramuscular (gluteus medius) administration.
- •History of or on-going high-risk behaviours that may put the participant at increased risk for HIV.
- •Past or intended use of over-the-counter or prescription medication including herbal medications.
- •Current enrollment or recent past participation in another investigational study.
- •Exposure to more than 4 investigational products within 12 months prior to dosing.
- •Alanine transaminase (ALT) ≥1.5x upper limit of normal (ULN), Total bilirubin ≥1.5x ULN (isolated total bilirubin >1.5xULN), and/or estimated creatinine clearance (eGFR) of <60 millilitre per minute (mL/min)/1.73 square meter (m^2).
- •History of or current infection with hepatitis B or hepatitis C.
- •Positive SARS-CoV-2 polymerase chain reaction test, having signs and symptoms, or having contact with known coronavirus disease 2019 (COVID-19) positive person/s in the 14 days prior to inpatient admission.
- •Use of tobacco or nicotine-containing products, regular alcohol consumption and/or regular use of known drugs of abuse.
- •Positive HIV antibody/antigen test.
- •Abnormal electrocardiogram (ECG) parameters.
- •Evidence of previous myocardial infarction, any conduction abnormality, any significant arrhythmia, non-sustained or sustained ventricular tachycardia, and/or sinus pauses (>3 seconds).
- •The participant has a tattoo or other dermatological condition overlying the location of injection or a prior history of silicone implants or fillers (gluteal) which may interfere with interpretation of injection site reactions or administration of study product.
研究组 & 干预措施
Part 1 Single Ascending Dose (SAD): Participants Receiving VH4004280
VH4004280 injections are administered subcutaneously (SC), SC+ rHuPH20, or intramuscularly (IM).
干预措施: VH4004280 (Drug)
Part 2 SAD: Participants Receiving VH4011499
VH4011499 injections are administered SC, SC+ rHuPH20, or IM.
干预措施: VH4011499 (Drug)
Part 2 Multiple Ascending Dose (MAD): Participants Receiving VH4011499
VH4011499 injections are administered IM.
干预措施: VH4011499 (Drug)
Part 1: Participants Receiving Placebo
Placebo injection is administered.
干预措施: Placebo (Drug)
Part 2: Participants Receiving Placebo
Placebo injection is administered.
干预措施: Placebo (Drug)
结局指标
主要结局
SAD: Change from Baseline in Liver Chemistry Parameters: Alkaline Phosphatase, AST, and ALT (International Units per liter)
时间窗: Baseline (Prior to Day 1) and up to Week 52
SAD: Change from Baseline in Liver Chemistry Parameters: Total Bilirubin and Direct Bilirubin (umol/L)
时间窗: Baseline (Prior to Day 1) and up to Week 52
MAD: Change from Baseline in Liver Chemistry Parameters: Alkaline Phosphatase, AST, and ALT (International Units per liter)
时间窗: Baseline (Prior to Day 1) and up to Week 56
SAD: Number of Participants with Maximum Toxicity Grade Change from Baseline in Liver Chemistry Parameters: Total Bilirubin, Direct Bilirubin, Alkaline Phosphatase, Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT)
时间窗: Up to Week 52
MAD: Number of Participants with Maximum Toxicity Grade Change from Baseline in Liver Chemistry Parameters: Total Bilirubin, Direct Bilirubin, Alkaline Phosphatase, Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT)
时间窗: Up to Week 56
SAD: Absolute Values of Liver Chemistry Parameters: Alkaline Phosphatase, Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) (International Units per liter)
时间窗: Up to Week 52
MAD: Absolute Values of Liver Chemistry Parameters: Alkaline Phosphatase, Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) (International Units per liter)
时间窗: Up to Week 56
SAD: Absolute Values of Liver Chemistry Parameters: Total Bilirubin and Direct Bilirubin (micromoles per liter [umol/L])
时间窗: Up to Week 52
MAD: Absolute Values of Liver Chemistry Parameters: Total Bilirubin and Direct Bilirubin (micromoles per liter [umol/L])
时间窗: Up to Week 56
MAD: Change from Baseline in Liver Chemistry Parameters: Total Bilirubin and Direct Bilirubin (umol/L)
时间窗: Baseline (Prior to Day 1) and up to Week 56
SAD: Number of Participants with Adverse Events (AEs) as per Severity
时间窗: Up to Week 52
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. Severity of Adverse Event will be assessed using Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS). DAIDS grading scale is used to grade the toxicity associated with injection site reactions (ISR) including injection site pain (or tenderness), erythema (or redness), induration (or swelling), and pruritis. The toxicity level is graded from grade 1(lowest toxicity) to 4 (highest toxicity). Higher grade indicates higher toxicity.
MAD: Number of Participants with Adverse Events (AEs) as per Severity
时间窗: Up to Week 56
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. Severity of Adverse Event will be assessed using Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS). DAIDS grading scale is used to grade the toxicity associated with injection site reactions (ISR) including injection site pain (or tenderness), erythema (or redness), induration (or swelling), and pruritis. The toxicity level is graded from grade 1(lowest toxicity) to 4 (highest toxicity). Higher grade indicates higher toxicity.
SAD: Number of Participants with Injection Site Reactions (ISR) AE by Grade Using the DAIDS Grading Scale
时间窗: Up to Week 52
DAIDS grading scale is used to grade the toxicity associated with injection site reactions (ISR) including injection site pain (or tenderness), erythema (or redness), induration (or swelling), and pruritis. The toxicity level is graded from grade 1(lowest toxicity) to 4 (highest toxicity). Higher grade indicates higher toxicity.
MAD: Number of Participants with Injection Site Reactions (ISR) AE by Grade Using the DAIDS Grading Scale
时间窗: Up to Week 56
DAIDS grading scale is used to grade the toxicity associated with injection site reactions (ISR) including injection site pain (or tenderness), erythema (or redness), induration (or swelling), and pruritis. The toxicity level is graded from grade 1(lowest toxicity) to 4 (highest toxicity). Higher grade indicates higher toxicity.
SAD: Duration of ISR (Days) AE
时间窗: Up to Week 52
Duration of ISR will be assessed as the time up to which a reaction related to injection site event is persistent.
MAD: Duration of ISR (Days) AE
时间窗: Up to Week 56
Duration of ISR will be assessed as the time up to which a reaction related to injection site event is persistent.
Area Under the Plasma-concentration Time curve from Time Zero to Infinity (AUC0-inf) of VH4004280
时间窗: Up to Week 52
Area Under the Plasma-concentration Time curve from Time Zero to Infinity (AUC0-inf) of VH4011499
时间窗: Up to Week 56
Maximum Observed Plasma Concentration (Cmax) of VH4004280
时间窗: Up to Week 52
Maximum Observed Plasma Concentration (Cmax) of VH4011499
时间窗: Up to Week 56
Time of Maximum Observed Plasma Concentration (tmax) of VH4004280
时间窗: Up to Week 52
Time of Maximum Observed Plasma Concentration (tmax) of VH4011499
时间窗: Up to Week 56
Apparent Terminal Half-life (t1/2) of VH4004280
时间窗: Up to Week 52
Apparent Terminal Half-life (t1/2) of VH4011499
时间窗: Up to Week 56
次要结局
未报告次要终点