A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of a Single Suspension Injection of Investigational Capsid Inhibitors Compared to Placebo in Healthy Adults

NCT06012136 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 218306
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 2

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.

Conditions

HIV Infections

Keywords

Healthy participants; Human Immunodeficiency Virus (HIV-1); VH4004280; VH4011499; Long-Acting Injection; Single ascending dose

Outcome Measures

Primary Outcomes (24)

• SAD: Number of Participants with Adverse Events (AEs) as per Severity

  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.

  Up to Week 52

• MAD: Number of Participants with Adverse Events (AEs) as per Severity

  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.

  Up to Week 56

• 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

  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.

  Up to Week 52

• MAD: Number of Participants with Injection Site Reactions (ISR) AE by Grade Using the DAIDS Grading Scale

  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.

  Up to Week 56

• SAD: Duration of ISR (Days) AE

  Duration of ISR will be assessed as the time up to which a reaction related to injection site event is persistent.

  Up to Week 52

• MAD: Duration of ISR (Days) AE

  Duration of ISR will be assessed as the time up to which a reaction related to injection site event is persistent.

  Up to Week 56

• 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

Study Arms (5)

Part 1 Single Ascending Dose (SAD): Participants Receiving VH4004280

EXPERIMENTAL

VH4004280 injections are administered subcutaneously (SC), SC+ rHuPH20, or intramuscularly (IM).

Drug: VH4004280

Part 1: Participants Receiving Placebo

PLACEBO COMPARATOR

Placebo injection is administered.

Drug: Placebo

Part 2 SAD: Participants Receiving VH4011499

EXPERIMENTAL

VH4011499 injections are administered SC, SC+ rHuPH20, or IM.

Drug: VH4011499

Part 2 Multiple Ascending Dose (MAD): Participants Receiving VH4011499

EXPERIMENTAL

VH4011499 injections are administered IM.

Drug: VH4011499

Part 2: Participants Receiving Placebo

PLACEBO COMPARATOR

Placebo injection is administered.

Drug: Placebo

Interventions

VH4004280 DRUG

VH4004280 will be administered.

Part 1 Single Ascending Dose (SAD): Participants Receiving VH4004280

Placebo DRUG

Placebo will be administered.

Part 1: Participants Receiving Placebo; Part 2: Participants Receiving Placebo

VH4011499 DRUG

VH4011499 will be administered.

Part 2 Multiple Ascending Dose (MAD): Participants Receiving VH4011499; Part 2 SAD: Participants Receiving VH4011499

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ViiV Healthcare: lead

Study Sites (2)

GSK Investigational Site

Las Vegas, Nevada, 89113, United States

Location

GSK Investigational Site

Austin, Texas, 78744, United States

Location

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2023
• First Posted: August 25, 2023
• Study Start: August 24, 2023
• Primary Completion (Estimated): June 9, 2026
• Study Completion (Estimated): June 9, 2026
• Last Updated: September 5, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

Locations

US (2)