First Time in Human Study of Long Acting VH4524184 Formulations

NCT06310551 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 218804
• Study Type: interventional
• Target: 268
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to identify 1 or more doses of parenterally administered VH4524184 that are safe, well tolerated and yield a PK drug exposure profile necessary to deliver a long-acting antiretroviral therapy for the treatment of HIV-1 infection.

Conditions

HIV Infections

Keywords

Safety; Tolerability; Parenteral; First Time in Human; Pharmacokinetics; Ascending Dose; Multiple Dose; Healthy Adults

Outcome Measures

Primary Outcomes (19)

• Percentage of participants reporting adverse events (AEs) and related AEs

  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. Related AE = AE assessed by the investigator as related to the study drug.

  From first study dose administration (Day 1) up to study end (Week 52 post last dose)

• Percentage of participants with AEs by severity

  Severity of AEs will be assessed using Division of AIDS Table for Grading the Severity of Adult 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.

  From first dose administration (Day 1) up to study end (Week 52 post last dose)

• Percentage of participants discontinuing the treatment due to AEs

  From first dose administration (Day 1) up to study end (Week 52 post last dose)

• Change from baseline in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase parameters

  The liver panel laboratory parameters are assessed after the administration of long-acting injectable (LAI) VH4524184.

  From first dose administration (Day 1) up to study end (Week 52 post last dose)

• Change from baseline in total bilirubin parameters

  The liver panel laboratory parameters are assessed after the administration of LAI VH4524184.

  From first dose administration (Day 1) up to study end (Week 52 post last dose)

• Change from baseline in international normalized ratio (INR) parameters

  The liver panel laboratory parameters are assessed after the administration of LAI VH4524184.

  From first dose administration (Day 1) up to study end (Week 52 post last dose)

• Maximum toxicity grade increase from baseline in ALT, AST and alkaline phosphatase

  From first dose administration (Day 1) up to study end (Week 52 post last dose)

• Maximum toxicity grade increase from baseline in total bilirubin

  From first dose administration (Day 1) up to study end (Week 52 post last dose)

• Maximum toxicity grade increase from baseline in INR

  From first dose administration (Day 1) up to study end (Week 52 post last dose)

• Percentage of participants reporting injection site reaction (ISR) AEs

  Assessed ISRs are pain, tenderness, infections, erythema, swelling, induration, or nodules (granulomas or cysts). Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, and Grade 4 = potentially life threatening.

  From first dose administration (Day 1) up to study end (Week 52 post last dose)

• Duration of injection site reaction AEs

  From first dose administration (Day 1) up to study end (Week 52 post last dose)

• Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinity time (AUC[0-inf]) of LAI VH4524184 following single dose administration

  From first dose administration (Day 1) up to study end (Week 52 post last dose)

• Area under the plasma drug concentration-time curve from zero (pre-dose) to the end of the dosing interval at steady state (AUC[0-t]) of LAI VH4524184 following multiple dose administration

  From first dose administration (Day 1) up to study end (Week 52 post last dose)

• Maximum observed plasma drug concentration (Cmax) of LAI VH4524184 following single dose administration

  From first dose administration (Day 1) up to study end (Week 52 post last dose)

• Cmax of LAI VH4524184 following multiple dose administration

  From first dose administration (Day 1) up to study end (Week 52 post last dose)

• Time to maximum observed plasma drug concentration (Tmax) of LAI VH4524184 following single dose administration

  From first dose administration (Day 1) up to study end (Week 52 post last dose)

• Tmax of LAI VH4524184 following multiple dose administration

  From first dose administration (Day 1) up to study end (Week 52 post last dose)

• Apparent terminal half-life (t1/2) of LAI VH4524184 following single dose administration

  From first dose administration (Day 1) up to study end (Week 52 post last dose)

• t1/2 of LAI VH4524184 following multiple dose administration

  From first dose administration (Day 1) up to study end (Week 52 post last dose)

Secondary Outcomes (1)

• Percentage of participants with treatment emergent Grade 3 or Grade 4 laboratory abnormalities

  From first dose administration of VH4524184 (Day 1) up to study end (Week 52 post last dose)

Study Arms (5)

Formulation A SC Group

EXPERIMENTAL

Participants receive a Formulation A starting dose of VH4524184 LAI subcutaneously (SC).

Drug: Oral VH4524184; Drug: VH4524184 Formulation A SC; Drug: Placebo Formulation A SC; Drug: rHuPH20

Formulation B SC Group

EXPERIMENTAL

Participants receive a Formulation B starting dose of VH4524184 LAI subcutaneously (SC).

Drug: Oral VH4524184; Drug: rHuPH20; Drug: VH4524184 Formulation B SC; Drug: Placebo Formulation B SC

Formulation A IM Group

EXPERIMENTAL

Participants receive a Formulation A starting dose of VH4524184 LAI intramuscularly (IM).

Drug: Oral VH4524184; Drug: VH4524184 Formulation A IM; Drug: Placebo Formulation A IM

Formulation B IM Group

EXPERIMENTAL

Participants receive a Formulation B starting dose of VH4524184 LAI intramuscularly (IM).

Drug: Oral VH4524184; Drug: VH4524184 Formulation B IM; Drug: Placebo Formulation B IM

Multiple doses Group

EXPERIMENTAL

VH4524184 LAI formulations administered SC or IM as single doses that achieve adequate PK exposure targets, may be evaluated for safety and tolerability as multiple doses.

Drug: Oral VH4524184; Drug: VH4524184 Formulation A SC; Drug: Placebo Formulation A SC; Drug: rHuPH20; Drug: VH4524184 Formulation B SC; Drug: Placebo Formulation B SC; Drug: VH4524184 Formulation A IM; Drug: Placebo Formulation A IM; Drug: VH4524184 Formulation B IM; Drug: Placebo Formulation B IM

Interventions

Oral VH4524184 DRUG

VH4524184 to be taken orally.

Formulation A IM Group; Formulation A SC Group; Formulation B IM Group; Formulation B SC Group; Multiple doses Group

VH4524184 Formulation A SC DRUG

Low (\<1mL) starting dose of VH4524184 LAI Formulation A administered subcutaneously.

Formulation A SC Group; Multiple doses Group

VH4524184 Formulation B SC DRUG

Starting dose of VH4524184 LAI Formulation B administered subcutaneously.

Formulation B SC Group; Multiple doses Group

Placebo Formulation B IM DRUG

Dose of Placebo Formulation B administered intramuscularly.

Formulation B IM Group; Multiple doses Group

Placebo Formulation A SC DRUG

Starting dose of Placebo Formulation A administered subcutaneously.

Formulation A SC Group; Multiple doses Group

rHuPH20 DRUG

Dose of rHuPH20 administered subcutaneously.

Also known as: PH20, Halozyme ENHANZE

Formulation A SC Group; Formulation B SC Group; Multiple doses Group

Placebo Formulation B SC DRUG

Starting dose of Placebo Formulation B administered subcutaneously.

Formulation B SC Group; Multiple doses Group

VH4524184 Formulation A IM DRUG

Starting dose VH4524184 LAI Formulation A administered intramuscularly.

Formulation A IM Group; Multiple doses Group

Placebo Formulation A IM DRUG

Dose of Placebo Formulation A administered intramuscularly.

Formulation A IM Group; Multiple doses Group

VH4524184 Formulation B IM DRUG

Starting dose VH4524184 LAI Formulation B administered intramuscularly.

Formulation B IM Group; Multiple doses Group

Eligibility Criteria

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

You may qualify if:

• Age
• Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
• Type of Participant and Characteristics
• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
• Participants who are negative for SARS-CoV-2, performed on admission/readmission to the Phase 1 unit, using an approved molecular test (PCR).
• Participants who are able to understand and comply with protocol requirements and timetables, instructions, and protocol-stated restrictions.
• Weight
• 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) for all cohorts except A11. For Cohort A11, body mass index within the range \>32.0 to 37.0 kg/m\^2 (inclusive).
• Sex and Contraceptive/Barrier Requirements
• Male or female
• Male Participants: No restrictions for male participants
• Participants of female sex assigned at birth:
• A participant of childbearing potential (POCBP) (female sex assigned at birth) is eligible to participate as long as the participant is not pregnant, breastfeeding and utilizes a highly effective method of contraception.
• A participant of non-childbearing potential (PONCBP) is eligible to participate if all other eligibility criteria are met.
• Informed Consent

You may not qualify if:

• Medical Conditions
• History or presence of clinical condition or disorder that could be capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study drug, interfering with the interpretation of data or would make the participant unsuitable for the study; unable to comply with dosing requirements; or unable to comply with study visits.
• Clinically significant abnormal blood pressure as determined by the investigator.
• 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.
• Medical history of cardiac arrhythmias or cardiac disease or a family and personal history of long QT syndrome.
• Underlying skin disease or disorder that would interfere with the administration of study product and/or assessment of injection site reactions.
• Clinically significant history of drug hypersensitivity, delayed-type hypersensitivity or severe hypersensitivity reactions, as well as history of /sensitivity to any of the study interventions including hyaluronidases.
• Current or anticipated need for chronic anti-coagulation except for the use of low dose acetylsalicylic acid (≤325 mg) or hereditary coagulation and platelet disorders such as hemophilia or Von Willebrand Disease.
• History of seizure.
• Any known or suspected pre-existing psychiatric condition, including depression, anxiety and insomnia/sleep disturbances, at the discretion of the investigator.
• Any positive (abnormal) response confirmed by the investigator or clinician (or qualified designee) administered C-SSRS at screening.
• Insufficient muscle mass (gluteus medius or thigh) to support IM dose administration in the opinion of the investigator.
• Presence of tattoos, implants or skin piercings that may interfere with the administration of study product and/or assessment of ISRs, if they occur.

Sponsors & Collaborators

• ViiV Healthcare: lead

Study Sites (3)

GSK Investigational Site

Lenexa, Kansas, 66219, United States

RECRUITING

GSK Investigational Site

San Antonio, Texas, 78209, United States

RECRUITING

GSK Investigational Site

Salt Lake City, Utah, 84124, United States

RECRUITING

MeSH Terms

Conditions

HIV Infections

Interventions

hyaluronidase PH-20

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

Central Study Contacts

US GSK Clinical Trials Call Center

CONTACT

877-379-3718; GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

CONTACT

+44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

Study Design

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

Study Record Dates

• First Submitted: March 5, 2024
• First Posted: March 15, 2024
• Study Start: March 21, 2024
• Primary Completion (Estimated): January 21, 2028
• Study Completion (Estimated): January 21, 2028
• Last Updated: April 20, 2026

Record last verified: 2026-04

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 asset(s) with development terminated 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 (3)