A Phase 1, Double-Blind (Sponsor-Unblinded), Placebo-Controlled, Randomized, Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Parenterally Administered VH5356136 in Adult Participants Without HIV
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 160
- 主要终点
- Number of participants with drug-related adverse events (AEs)
研究概览
简要总结
The study aims to evaluate the safety, tolerability and pharmacokinetic (PK) properties of a single dose of VH5356136 in adult participants without human immunodeficiency virus (HIV). This study will be conducted following the availability of initial safety and PK clinical data from formulation of the parent drug VH4524184.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
This is a double-blind (sponsor-unblinded) study.
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 must be 18 to 55 years of age inclusive at the time of signing the informed consent form (ICF).
- •Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
- •Participants who are able to understand and comply with protocol requirements and timetables, instructions, and protocol-stated restrictions.
- •Body weight ≥50.0 kg (110 lbs) for men and ≥45.0 kg (99 lbs) for women and body mass index within the range 18.5 to 32.0 kg/m^2 (inclusive).
- •Participants of any sex (male or female) are eligible. A female participant (female sex assigned at birth) is eligible to participate if they are a person of non-childbearing potential (PONCBP).
- •Capable of providing signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in the protocol.
- •The criteria presented above represent a subset of the key inclusion criteria for the study. Additional criteria, restrictions, and eligibility requirements may apply as specified in the study protocol.
排除标准
- •History or presence of, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, 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.
- •History of drug hypersensitivity, delayed-type hypersensitivity or severe hypersensitivity reaction or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates study participation.
- •History of or on-going high-risk behaviors that may put the participant at increased risk for HIV acquisition in the opinion of the investigator.
- •Any preexisting physical or mental condition which, in the opinion of the investigator or the medical monitor, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant.
- •Previous exposure to the parent molecule VH
- •Past or intended use of over-the-counter or prescription medication within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to dosing and for the duration of the study.
- •Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of study intervention.
- •Participants receiving any protocol-prohibited medication and who are unwilling or unable to switch to an alternate medication.
- •Current enrolment or participation in another clinical study.
- •Any acute laboratory abnormality at screening, which, in the opinion of the investigator, would preclude the participant's participation in the study of an investigational compound.
- •Positive HIV antibody/antigen test.
- •History of clinically relevant hepatitis within the last 6 months.
- •Positive hepatitis B or hepatitis C test.
- •Clinically significant cardiovascular disease..
- •QT interval corrected for heart rate according to Fridericia's formula (QTcF) >450 milliseconds (msec) and >480 msec (bundle branch block).
- •Blood pressure (BP) >140/90 (systolic BP/diastolic BP [SBP/DBP]).
- •Resting heart rate (HR) <50 or >100 beats per minute (bpm) when vital signs are measured at Screening or Check-in.
- •The criteria presented above represent a subset of the key exclusion criteria for the study. Additional criteria, restrictions, and eligibility requirements may apply as specified in the study protocol.
研究组 & 干预措施
VH5356136 Formulation 1
Participants will receive a single dose of VH5356136 Formulation 1 administered on Day 1.
干预措施: VH5356136 Formulation 1 (Drug)
Placebo for VH5356136 Formulation 1
Participants will receive a single dose of placebo for VH5356136 Formulation 1 administered on Day 1.
干预措施: Placebo for VH5356136 Formulation 1 (Drug)
VH5356136 Formulation 2
Participants will receive a single dose of VH5356136 Formulation 2 administered on Day 1.
干预措施: VH5356136 Formulation 2 (Drug)
Placebo for VH5356136 Formulation 2
Participants will receive a single dose of placebo for VH5356136 Formulation 2 administered on Day 1.
干预措施: Placebo for VH5356136 Formulation 2 (Drug)
结局指标
主要结局
Number of participants with drug-related adverse events (AEs)
时间窗: From Day 1 to Month 18
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. A drug-related AE is an AE that, in the opinion of the investigator, is related to one of the study interventions.
Time to maximum observed plasma drug concentration (tmax) for VH5356136
时间窗: From Day 1 (pre-dose) up to Month 18 post-dose
Tmax for VH4524184
时间窗: From Day 1 (pre-dose) up to Month 18 post-dose
Terminal half-life (t1/2) for VH5356136
时间窗: From Day 1 (pre-dose) up to Month 18 post-dose
t1/2 for VH4524184
时间窗: From Day 1 (pre-dose) up to Month 18 post-dose
Number of participants with Grade 2 to Grade 5 AEs
时间窗: From Day 1 to Month 18
The grading of AEs is performed based on the Division of Acquired Immunodeficiency Syndrome (DAIDS) grading scale, here Grade 2 = moderate, Grade 3=severe, Grade 4 = potentially life-threatening, Grade 5 = death.
Number of participants with serious adverse events (SAEs)
时间窗: From Day 1 to Month 18
An SAE is defined as any untoward medical occurrence that results in death, are life threatening, require hospitalization or prolongation of hospitalization or results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, is considered or defined as an important medical event, or abnormal pregnancy outcomes.
Area under the concentration time curve from zero (pre-dose) to the last quantifiable concentration (post dose) (AUC[0-tlast]) for VH5356136
时间窗: From Day 1 (pre-dose) up to Month 18 post-dose
AUC(0-tlast) for VH4524184
时间窗: From Day 1 (pre-dose) up to Month 18 post-dose
Maximum plasma concentration (Cmax) for VH5356136
时间窗: From Day 1 (pre-dose) up to Month 18 post-dose
Cmax for VH4524184
时间窗: From Day 1 (pre-dose) up to Month 18 post-dose
次要结局
- Number of participants with Grade 3 and Grade 4 laboratory abnormalities(From Day 1 (pre-dose) up to Month 18 post-dose)