A Phase 1 Double-blind (Sponsor-unblinded), Placebo-controlled, Randomized, Single Dose Escalation Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of VH4367310 Administered to Healthy Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 112
- 主要终点
- Area under the concentration time curve from time zero to last quantifiable time point (AUC0-tlast) of VH4367310 and CAB
研究概览
简要总结
This study evaluates the PK, safety, and tolerability of a single increasing dose of VH4367310, a cabotegravir (CAB) prodrug, when administered intramuscularly in healthy adult participants 18 to 55 years of age.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Double blind
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
- •Participant must be greater than or equal to (>=) 18 years and less than or equal to (<=) 55 years of age, at the time of signing the informed consent.
- •Participants who are overtly healthy as determined by medical evaluation.
- •Body weight >=40 kg and BMI within the range >=18 to <=32 kg/m^
- •Participants may be male or female. Male participants are eligible to participate if they agree to the contraception requirements of the study during the study intervention period and for at least 90 days after the last dose of study intervention. Participants assigned female at birth are eligible to participate if they are a participant of non-childbearing potential (PONCBP).
- •Capable of giving written informed consent.
排除标准
- •Current presence or history 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.
- •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.
- •Unstable liver disease or known hepatic or biliary abnormalities.
- •History of clinically relevant hepatitis within last 6 months.
- •History of cirrhosis with or without viral hepatitis co-infection.
- •Participants determined by the investigator to have a high risk of seizures.
- •Participant who poses a significant suicidality risk.
- •Current or anticipated need for chronic anti-coagulation therapy.
- •Hereditary coagulation or platelet disorders.
- •Any acute laboratory abnormality at screening that would preclude participation or exclusionary laboratory value.
- •Abnormal blood pressure.
- •ALT >1.5x upper limit of normal (ULN). Total bilirubin >1.5x ULN; Participants with Gilbert's syndrome can be included with total bilirubin >1.5x ULN as long as direct bilirubin is <=1.5x ULN.
- •Hemoglobin <12.5 g/dL for men and <11 g/dL for women.
- •Creatinine clearance (eGFR) of <60 millilitre per minute (mL/min)/1.73 square meter (m^2).
- •Presence of HbsAg and/or HbcAb at screening or within 3 months prior to first dose of study intervention.
- •Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention.
- •Positive HIV antibody/antigen test (HIV-1 ± HIV-2).
- •Current enrolment or past participation in another investigational study in which an experimental drug or experimental vaccine was administered.
- •Participants receiving any protocol-prohibited medication and who are unwilling or unable to switch to an alternate medication.
- •Participation in the study would result in loss of blood or blood products in excess of 500 mL within 56 days.
- •Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
- •Past participation in another investigational clinical study in which long-acting CAB was administered or any CAB use for pre-exposure prophylaxis (PrEP).
- •History of sensitivity to any of the study interventions (or components thereof), a history of drug allergy or another allergy.
- •Participant has an implant/enhancement (including fillers); or tattoo or other dermatological condition overlying the area for IM or SC injection or any other area which may significantly interfere with interpretation of injection site reactions.
- •History of or ongoing high-risk behaviors that may put the participant at increased risk for HIV.
- •Regular alcohol consumption within 6 months prior to the study defined as: An average weekly intake of >14 units for males or >7 units for females.
- •Regular use of known drugs of abuse.
- •Positive pre-study drug/alcohol screen.
- •Cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
- •Any other clinical condition, behaviour or prior therapy that, in the opinion of the investigator, would make the participant unsuitable for the study; unable to comply with dosing requirements; or unable to comply with study visits.
研究组 & 干预措施
Placebo Group
Participants will be randomized to receive placebo on Day 1.
干预措施: Placebo (Drug)
VH4367310 Group
Participants will be randomized to receive a single injection of VH4367310 on Day 1.
干预措施: VH4367310 (Drug)
结局指标
主要结局
Area under the concentration time curve from time zero to last quantifiable time point (AUC0-tlast) of VH4367310 and CAB
时间窗: Up to Week 72
Maximum observed plasma concentration (Cmax) of VH4367310 and CAB
时间窗: Up to Week 72
Time to maximum observed plasma concentration (Tmax) of VH4367310 and CAB
时间窗: Up to Week 72
Number of participants with drug-related adverse events (AEs)
时间窗: Up to Week 72
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.
Number of participants with AEs as per severity
时间窗: Up to Week 72
Severity is graded according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) grading criteria, where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening, Grade 5 = Death.
Number of participants with drug-related serious adverse events (SAEs)
时间窗: Up to Week 72
An SAE is defined as any untoward medical occurrence that results in death, is life threatening, requires hospitalization or prolongs existing hospitalization, results in disability/incapacity or other medically significant events.
次要结局
未报告次要终点