Clinical trial NCT06012136: A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of a Single Suspension Injection of Investigational Capsid Inhibitors Compared to Placebo in Healthy Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: HIV Infections
Keywords: Healthy participants
Human Immunodeficiency Virus (HIV-1)
VH4004280
VH4011499
Long-Acting Injection
Single ascending dose
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
First posted: 2023-08-25
Enrollment: 208
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 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.


Eligibility criteria: Inclusion Criteria:

* 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 1.
* Male or female participants 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 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.

Primary outcomes:
measure: SAD: Number of Participants with Adverse Events (AEs) as per Severity
timeFrame: Up to Week 52
measure: MAD: Number of Participants with Adverse Events (AEs) as per Severity
timeFrame: Up to Week 56
measure: SAD: Absolute Values of Liver Chemistry Parameters: Total Bilirubin and Direct Bilirubin (micromoles per liter [umol/L])
timeFrame: Up to Week 52
measure: MAD: Absolute Values of Liver Chemistry Parameters: Total Bilirubin and Direct Bilirubin (micromoles per liter [umol/L])
timeFrame: Up to Week 56
measure: SAD: Change from Baseline in Liver Chemistry Parameters: Total Bilirubin and Direct Bilirubin (umol/L)
timeFrame: Baseline (Prior to Day 1) and up to Week 52
measure: MAD: Change from Baseline in Liver Chemistry Parameters: Total Bilirubin and Direct Bilirubin (umol/L)
timeFrame: Baseline (Prior to Day 1) and up to Week 56
measure: 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)
timeFrame: Up to Week 52
measure: 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)
timeFrame: Up to Week 56
measure: SAD: Absolute Values of Liver Chemistry Parameters: Alkaline Phosphatase, Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) (International Units per liter)
timeFrame: Up to Week 52
measure: MAD: Absolute Values of Liver Chemistry Parameters: Alkaline Phosphatase, Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) (International Units per liter)
timeFrame: Up to Week 56
measure: SAD: Change from Baseline in Liver Chemistry Parameters: Alkaline Phosphatase, AST, and ALT (International Units per liter)
timeFrame: Baseline (Prior to Day 1) and up to Week 52
measure: MAD: Change from Baseline in Liver Chemistry Parameters: Alkaline Phosphatase, AST, and ALT (International Units per liter)
timeFrame: Baseline (Prior to Day 1) and up to Week 56
measure: SAD: Number of Participants with Injection Site Reactions (ISR) AE by Grade Using the DAIDS Grading Scale
timeFrame: Up to Week 52
measure: MAD: Number of Participants with Injection Site Reactions (ISR) AE by Grade Using the DAIDS Grading Scale
timeFrame: Up to Week 56
measure: SAD: Duration of ISR (Days) AE
timeFrame: Up to Week 52
measure: MAD: Duration of ISR (Days) AE
timeFrame: Up to Week 56
measure: Area Under the Plasma-concentration Time curve from Time Zero to Infinity (AUC0-inf) of VH4004280
timeFrame: Up to Week 52
measure: Area Under the Plasma-concentration Time curve from Time Zero to Infinity (AUC0-inf) of VH4011499
timeFrame: Up to Week 56
measure: Maximum Observed Plasma Concentration (Cmax) of VH4004280
timeFrame: Up to Week 52
measure: Maximum Observed Plasma Concentration (Cmax) of VH4011499
timeFrame: Up to Week 56
measure: Time of Maximum Observed Plasma Concentration (tmax) of VH4004280
timeFrame: Up to Week 52
measure: Time of Maximum Observed Plasma Concentration (tmax) of VH4011499
timeFrame: Up to Week 56
measure: Apparent Terminal Half-life (t1/2) of VH4004280
timeFrame: Up to Week 52
measure: Apparent Terminal Half-life (t1/2) of VH4011499
timeFrame: Up to Week 56
Secondary outcomes:
Other outcomes:
Locations:
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
Study officials:
References: