HIV Infections
Conditions
Keywords
Healthy participants, Human Immunodeficiency Virus (HIV-1), VH4004280, VH4011499, Long-Acting Injection, Single ascending dose
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.
Interventions
Sponsors
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SAD: Number of Participants with Adverse Events (AEs) as per Severity | Up to Week 52 | 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. Severity of Adverse Event will be assessed using Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS). DAIDS grading scale is used to grade the toxicity associated with injection site reactions (ISR) including injection site pain (or tenderness), erythema (or redness), induration (or swelling), and pruritis. The toxicity level is graded from grade 1(lowest toxicity) to 4 (highest toxicity). Higher grade indicates higher toxicity. |
| MAD: Number of Participants with Adverse Events (AEs) as per Severity | Up to Week 56 | 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. Severity of Adverse Event will be assessed using Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS). DAIDS grading scale is used to grade the toxicity associated with injection site reactions (ISR) including injection site pain (or tenderness), erythema (or redness), induration (or swelling), and pruritis. The toxicity level is graded from grade 1(lowest toxicity) to 4 (highest toxicity). Higher grade indicates higher toxicity. |
| SAD: Absolute Values of Liver Chemistry Parameters: Total Bilirubin and Direct Bilirubin (micromoles per liter [umol/L]) | Up to Week 52 | — |
| MAD: Absolute Values of Liver Chemistry Parameters: Total Bilirubin and Direct Bilirubin (micromoles per liter [umol/L]) | Up to Week 56 | — |
| SAD: Change from Baseline in Liver Chemistry Parameters: Total Bilirubin and Direct Bilirubin (umol/L) | Baseline (Prior to Day 1) and up to Week 52 | — |
| MAD: Change from Baseline in Liver Chemistry Parameters: Total Bilirubin and Direct Bilirubin (umol/L) | Baseline (Prior to Day 1) and up to Week 56 | — |
| 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) | Up to Week 52 | — |
| 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) | Up to Week 56 | — |
| SAD: Absolute Values of Liver Chemistry Parameters: Alkaline Phosphatase, Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) (International Units per liter) | Up to Week 52 | — |
| MAD: Absolute Values of Liver Chemistry Parameters: Alkaline Phosphatase, Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) (International Units per liter) | Up to Week 56 | — |
| SAD: Change from Baseline in Liver Chemistry Parameters: Alkaline Phosphatase, AST, and ALT (International Units per liter) | Baseline (Prior to Day 1) and up to Week 52 | — |
| MAD: Change from Baseline in Liver Chemistry Parameters: Alkaline Phosphatase, AST, and ALT (International Units per liter) | Baseline (Prior to Day 1) and up to Week 56 | — |
| SAD: Number of Participants with Injection Site Reactions (ISR) AE by Grade Using the DAIDS Grading Scale | Up to Week 52 | DAIDS grading scale is used to grade the toxicity associated with injection site reactions (ISR) including injection site pain (or tenderness), erythema (or redness), induration (or swelling), and pruritis. The toxicity level is graded from grade 1(lowest toxicity) to 4 (highest toxicity). Higher grade indicates higher toxicity. |
| MAD: Number of Participants with Injection Site Reactions (ISR) AE by Grade Using the DAIDS Grading Scale | Up to Week 56 | DAIDS grading scale is used to grade the toxicity associated with injection site reactions (ISR) including injection site pain (or tenderness), erythema (or redness), induration (or swelling), and pruritis. The toxicity level is graded from grade 1(lowest toxicity) to 4 (highest toxicity). Higher grade indicates higher toxicity. |
| SAD: Duration of ISR (Days) AE | Up to Week 52 | Duration of ISR will be assessed as the time up to which a reaction related to injection site event is persistent. |
| MAD: Duration of ISR (Days) AE | Up to Week 56 | Duration of ISR will be assessed as the time up to which a reaction related to injection site event is persistent. |
| Area Under the Plasma-concentration Time curve from Time Zero to Infinity (AUC0-inf) of VH4004280 | Up to Week 52 | — |
| Area Under the Plasma-concentration Time curve from Time Zero to Infinity (AUC0-inf) of VH4011499 | Up to Week 56 | — |
| Maximum Observed Plasma Concentration (Cmax) of VH4004280 | Up to Week 52 | — |
| Maximum Observed Plasma Concentration (Cmax) of VH4011499 | Up to Week 56 | — |
| Time of Maximum Observed Plasma Concentration (tmax) of VH4004280 | Up to Week 52 | — |
| Time of Maximum Observed Plasma Concentration (tmax) of VH4011499 | Up to Week 56 | — |
| Apparent Terminal Half-life (t1/2) of VH4004280 | Up to Week 52 | — |
| Apparent Terminal Half-life (t1/2) of VH4011499 | Up to Week 56 | — |
Countries
United States
Outcome results
None listed