Clinical trial NCT06724640: A Study to Assess the Safety, Tolerability, and Pharmacokinetics of VH4011499 Compared to Placebo in Adults Without HIV
Official title: A Phase 1 Double-Blind (Sponsor-unblinded), Placebo-Controlled, Randomized, Single Dose Escalation Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Parenterally Administered Long-acting Formulations of VH4011499 in Adults Without HIV
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: HIV Infections
Keywords: Human Immunodeficiency Virus (HIV)
VH4011499
Safety
Tolerability
Pharmacokinetics
Healthy participants
Long-Acting Injection
Single ascending dose
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
First posted: 2024-12-09
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate safety and tolerability following single ascending subcutaneous (SC) and intramuscular (IM) doses of VH4011499 in participants without HIV. The study will also describe the pharmacokinetics following single ascending SC and IM doses of VH4011499 in participants without HIV.


Eligibility criteria: Inclusion Criteria:

* Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
* Participants who are overtly healthy.
* Male or female of non-childbearing potential.
* Capable of giving signed informed consent.

Exclusion Criteria:

* 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 clinically relevant hepatitis within last 6 months.
* Patients with chronic hepatitis B infection.
* 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 VH4011499 intramuscular administration will be excluded.
* History of or on-going high-risk behaviors that may put the participant at increased risk for HIV acquisition.
* Any preexisting physical or mental condition which 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.
* Past or intended use over-the-counter or prescription medication (including herbal medications) within 7 days prior to dosing
* Exposure to more than 4 new investigational products within 12 months prior to the first dosing day.
* Current enrollment or recent past participation in another investigational study.
* Positive HIV antibody/antigen test.
* ALT more than or equal to (\>=)1.5x upper limit of normal (ULN), Total bilirubin \>=1.5x ULN (isolated total bilirubin more than (\>)1.5xULN), and/or estimated creatinine clearance (eGFR) of less than (\<)60 millilitre per minute (mL/min)/1.73 square meter (m\^2).
* Regular use of tobacco or nicotine-containing products, regular alcohol consumption and/or use of known drugs of abuse.
* QT interval corrected for heart rate according to Fridericia's formula (QTcF) \>450 msec.
* 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 which may interfere with interpretation of ISRs or administration of study product.

Primary outcomes:
measure: Number of participants with adverse events (AEs), including Injection Site Reaction (ISR) AEs, as per severity of Grade 2-5 using the DAIDS grading scale
timeFrame: Up to Week 78
measure: Area under the plasma-concentration time curve from time zero to infinity (AUC0-inf) of VH4011499
timeFrame: Up to Week 78
measure: Maximum observed plasma concentration (Cmax) of VH4011499
timeFrame: Up to Week 78
measure: Time to maximum observed plasma concentration (tmax) of VH4011499
timeFrame: Up to Week 78
measure: Apparent terminal half-life (t1/2) of VH4011499
timeFrame: Up to Week 78
Secondary outcomes:
measure: Absolute values of liver chemistry parameters: total bilirubin and direct bilirubin (micromoles per liter [umol/L])
timeFrame: At Day 4, Day 10, Week 4, Week 24 and Week 48
measure: Change from baseline in liver chemistry parameters: total bilirubin and direct bilirubin (umol/L)
timeFrame: At Day 4, Day 10, Week 4, Week 24 and Week 48 compared to Baseline (Prior to Day 1)
measure: Number of participants with maximum toxicity grade change from baseline in liver chemistry parameters: total bilirubin, direct bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT)
timeFrame: Baseline (Prior to Day 1) and Up to Week 78
measure: Absolute values of liver chemistry parameters: ALP, AST, and ALT (International Units per Liter [IU/L])
timeFrame: At Day 4, Day 10, Week 4, Week 24 and Week 48
measure: Change from Baseline in Liver Chemistry Parameters: ALP, AST, and ALT (IU/L)
timeFrame: At Day 4, Day 10, Week 4, Week 24 and Week 48 compared to Baseline (Prior to Day 1)
measure: Number of participants with AEs (including ISR AEs) as per severity of all grades using the DAIDS grading scale
timeFrame: Up to Week 78
measure: Duration of ISR (Days) AEs by grade using the DAIDS grading scale
timeFrame: Up to Week 78
Other outcomes:
Locations:
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
Study officials:
References: