HIV Infections
Conditions
Keywords
VH5356136, VH4524184, Safety, Tolerability, HIV, Parenteral administration, Pharmacokinetics, Ascending Dose
Brief summary
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.
Interventions
DRUGVH5356136 Formulation 1
Participants will receive VH5356136 Formulation 1 on Day 1.
DRUGVH5356136 Formulation 2
Participants will receive VH5356136 Formulation 2 on Day 1.
DRUGPlacebo for VH5356136 Formulation 1
Participants will receive placebo for VH5356136 Formulation 1 on Day 1.
DRUGPlacebo for VH5356136 Formulation 2
Participants will receive placebo for VH5356136 Formulation 2 on Day 1.
Sponsors
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
This is a double-blind (sponsor-unblinded) study.
Intervention model description
Sequential Groups in a Parallel Design
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* 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.
Exclusion criteria
* 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 VH4524184. * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with drug-related adverse events (AEs) | 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. |
| Number of participants with Grade 2 to Grade 5 AEs | 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) | 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 | From Day 1 (pre-dose) up to Month 18 post-dose | — |
| AUC(0-tlast) for VH4524184 | From Day 1 (pre-dose) up to Month 18 post-dose | — |
| Maximum plasma concentration (Cmax) for VH5356136 | From Day 1 (pre-dose) up to Month 18 post-dose | — |
| Cmax for VH4524184 | From Day 1 (pre-dose) up to Month 18 post-dose | — |
| Time to maximum observed plasma drug concentration (tmax) for VH5356136 | From Day 1 (pre-dose) up to Month 18 post-dose | — |
| Tmax for VH4524184 | From Day 1 (pre-dose) up to Month 18 post-dose | — |
| Terminal half-life (t1/2) for VH5356136 | From Day 1 (pre-dose) up to Month 18 post-dose | — |
| t1/2 for VH4524184 | From Day 1 (pre-dose) up to Month 18 post-dose | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Grade 3 and Grade 4 laboratory abnormalities | From Day 1 (pre-dose) up to Month 18 post-dose | The laboratory abnormalities are assessed using the DAIDS grading scale, where Grade 3 = severe and Grade 4 = potentially life-threatening. |
Contacts
CONTACTUS GSK Clinical Trials Call Center
CONTACTEU GSK Clinical Trials Call Center
Outcome results
None listed