A Study to Investigate Safety, Tolerability, and Pharmacokinetics (PK) of VH4524184 and the Potential for Changes in Cytochrome P450 3A (CYP3A) Activity

NCT ID: NCT05631704

Last Updated: 2023-01-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

105 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-12-02

Study Completion Date

2023-08-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This study is designed to investigate the safety, tolerability and PK of VH4524184 (GSK4524184) and the potential of VH4524184 to inhibit or induce CYP3A activity in healthy participants.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

HIV Infections

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

First-time-in-human GSK4524184 Healthy volunteers Multiple Ascending Dose Single Ascending Dose VH4524184

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Participants will receive escalating doses of VH4524184 or placebo in Part 1 and Part 2 of the study. In Part 3, participants will receive VH4524184 under fasted and fed conditions.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
This will be a double blind study.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Part 1: Cohort 1: Participants receiving VH4524184 DL1

Eligible participants will receive VH4524184 Dose Level 1 (DL1) during Cohort 1 of Part 1 of the study.

Group Type EXPERIMENTAL

VH4524184

Intervention Type DRUG

VH4524184 will be administered.

Part 1: Cohort 1: Participants receiving Placebo

Eligible participants will receive Placebo matching VH4524184 DL1 during Cohort 1 of Part 1 of the study.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo will be administered.

Part 1: Cohort 2: Participants receiving VH4524184 DL2

Eligible participants will receive VH4524184 DL2 during Cohort 2 of Part 1 of the study.

Group Type EXPERIMENTAL

VH4524184

Intervention Type DRUG

VH4524184 will be administered.

Part 1: Cohort 2: Participants receiving Placebo

Eligible participants will receive Placebo matching VH4524184 DL2 during Cohort 2 of Part 1 of the study.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo will be administered.

Part 1: Cohort 3: Participants receiving VH4524184 DL3

Eligible participants will receive VH4524184 DL3 during Cohort 3 of Part 1 of the study.

Group Type EXPERIMENTAL

VH4524184

Intervention Type DRUG

VH4524184 will be administered.

Part 1: Cohort 3: Participants receiving Placebo

Eligible participants will receive Placebo matching VH4524184 DL3 during Cohort 3 of Part 1 of the study.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo will be administered.

Part 1: Cohort 4: Participants receiving VH4524184 DL4

Eligible participants will receive VH4524184 DL4 during Cohort 4 of Part 1 of the study.

Group Type EXPERIMENTAL

VH4524184

Intervention Type DRUG

VH4524184 will be administered.

Part 1: Cohort 4: Participants receiving Placebo

Eligible participants will receive Placebo matching VH4524184 DL4 during Cohort 4 of Part 1 of the study.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo will be administered.

Part 1: Cohort 5: Participants receiving VH4524184 DL5

Eligible participants will receive VH4524184 DL5 during Cohort 5 (optional) of Part 1 of the study.

Group Type EXPERIMENTAL

VH4524184

Intervention Type DRUG

VH4524184 will be administered.

Part 1: Cohort 5: Participants receiving Placebo

Eligible participants will receive Placebo matching VH4524184 DL5 during Cohort 5 (optional) of Part 1 of the study.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo will be administered.

Part 1: Cohort 6: Participants receiving VH4524184 DL6

Eligible participants will receive VH4524184 DL6 during Cohort 6 (optional) of Part 1 of the study.

Group Type EXPERIMENTAL

VH4524184

Intervention Type DRUG

VH4524184 will be administered.

Part 1: Cohort 6: Participants receiving Placebo

Eligible participants will receive Placebo matching VH4524184 DL6 during Cohort 6 (optional) of Part 1 of the study.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo will be administered.

Part 2: Cohort 7: Participants receiving VH4524184 RL1

Eligible participants will receive VH4524184 Repeat dose Level 1 (RL1) during Cohort 7 (Part 2) of the study.

Group Type EXPERIMENTAL

VH4524184

Intervention Type DRUG

VH4524184 will be administered.

Part 2: Cohort 7: Participants receiving Placebo

Eligible participants will receive Placebo matching VH4524184 RL1 during Cohort 7 (Part 2) of the study.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo will be administered.

Part 2: Cohort 8: Participants receiving VH4524184 RL2

Eligible participants will receive VH4524184 RL2 during Cohort 8 (Part 2) of the study. If Cohort 8 is the highest Part 2 dose cohort, participants may also receive midazolam probe before and following repeat dose administration of VH4524184

Group Type EXPERIMENTAL

VH4524184

Intervention Type DRUG

VH4524184 will be administered.

Midazolam

Intervention Type DRUG

Midazolam will be administered in the highest dose cohort in Part 2 (Cohorts 8 or 9).

Part 2: Cohort 8: Participants receiving Placebo

Eligible participants will receive Placebo matching VH4524184 RL2 during Cohort 8 (Part 2) of the study. If Cohort 8 is the highest Part 2 dose cohort, participants may also receive midazolam probe before and following repeat dose administration of Placebo matching VH4524184.

Group Type PLACEBO_COMPARATOR

Midazolam

Intervention Type DRUG

Midazolam will be administered in the highest dose cohort in Part 2 (Cohorts 8 or 9).

Placebo

Intervention Type DRUG

Placebo will be administered.

Part 2: Cohort 9: Participants receiving VH4524184 RL3

Eligible participants will receive VH4524184 RL3 during Cohort 9 (Part 2) (optional) of the study. If Cohort 9 is the highest Part 2 dose cohort, participants may also receive midazolam probe before and following repeat dose administration of VH4524184.

Group Type EXPERIMENTAL

VH4524184

Intervention Type DRUG

VH4524184 will be administered.

Midazolam

Intervention Type DRUG

Midazolam will be administered in the highest dose cohort in Part 2 (Cohorts 8 or 9).

Part 2: Cohort 9: Participants receiving Placebo

Eligible participants will receive Placebo matching VH4524184 RL3 during Cohort 9 (Part 2) (optional) of the study. If Cohort 9 is the highest Part 2 dose cohort, participants may also receive midazolam probe before and following repeat dose administration of Placebo matching VH4524184.

Group Type PLACEBO_COMPARATOR

Midazolam

Intervention Type DRUG

Midazolam will be administered in the highest dose cohort in Part 2 (Cohorts 8 or 9).

Placebo

Intervention Type DRUG

Placebo will be administered.

Part 3: Cohort 10: VH4524184 Fasted/ VH4524184 Fed

Eligible participants will receive VH4524184 under fasted condition in Treatment Period 1 followed by VH4524184 under fed condition in Treatment Period 2 during Cohort 10 (Part 3) of the study. Treatment Periods will be separated by a washout period.

Group Type EXPERIMENTAL

VH4524184

Intervention Type DRUG

VH4524184 will be administered.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

VH4524184

VH4524184 will be administered.

Intervention Type DRUG

Midazolam

Midazolam will be administered in the highest dose cohort in Part 2 (Cohorts 8 or 9).

Intervention Type DRUG

Placebo

Placebo will be administered.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Participant must be 18 to 50 years of age.
* Participants who are overtly healthy.
* Body weight \>=50.0 kilograms (kg) (110 pounds \[lbs\]) for men and \>=45.0 kg (99 lbs) for women and body mass index within the range 18.5 to 32.0 kilograms per meter square (kg/m\^2) (inclusive).
* Male or female. Male Participants: No contraceptive restrictions for male participants. Female Participants: A female participant (female sex assigned at birth) is eligible to participate if she is not pregnant, or breastfeeding and is not physically able to have a baby.

Exclusion Criteria

* History or presence of clinical condition that could significantly alter how medicines are absorbed, broken down or eliminated from the body; be risky to the participant, or make it difficult to interpret the data from the study.
* Pre-existing clinically relevant gastro-intestinal disorders.
* Abnormal blood pressure.
* Certain blood or other cancers within the past 5 years.
* Breast cancer within the past 10 years
* Current or chronic history of liver disease or liver or bile tract abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* QT interval corrected for heart rate according to Fridericia's formula (QTcF) \>450 milliseconds (msec).
* Medical history of cardiac arrhythmias or cardiac disease or a family and personal history of long QT syndrome.
* History of seizure
* Any known or suspected pre-existing psychiatric condition, including depression, anxiety and insomnia/sleep disturbances.
* Any positive (abnormal) response to the Columbia Suicide Severity Rating Scale (CSSRS).
* Past or intended use of over-the-counter or prescription medication within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to dosing and for the duration of the study.
* Receipt of any live vaccine(s) or vaccines against Coronavirus disease 2019 (Covid-19) within 28 days prior to screening or plans to receive such vaccines during the study.
* Exposure to more than 4 new investigational products (including long-acting investigational products) within 12 months prior to the first dosing day.
* Current enrollment or past participation in another investigational study in which an investigational intervention (e.g., drug, human blood product, monoclonal antibody, vaccine, invasive device) was administered within the last 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) before signing of consent (OR screening) any other clinical study.
* Participation in the study would result in loss of blood or blood products in excess of 500 milliliters (mL) over a 56-day period.
* Current enrollment or past participation in this clinical study.
* Estimated Glomerular Filtration Rate (eGFR) \<90 milliliters per minute (mL/min) (calculated using Chronic Kidney Disease Epidemiology Collaboration equation) or serum creatinine \>1.1 times Upper limit of normal (ULN).
* Hemoglobin \<12.5 grams per deciliter (g/dL) for men and \<11 g/dL for women
* ALT or AST \>1.5 times ULN
* Total bilirubin \>1.5 times ULN (isolated bilirubin \>1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent \[%\]).
* Any significant arrhythmia or Electrocardiogram (ECG) finding
* Presence of hepatitis B surface antigen (HBsAg) at screening.
* Positive Hepatitis C antibody test result at screening
* Positive pre-study drug/alcohol screen.
* Positive human immunodeficiency virus (HIV) antibody test.
* Regular alcohol consumption within 6 months prior to the study
* Regular use of known drugs of abuse
* Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening and at admission.
* Sensitivity to the study drug, or components thereof, midazolam (For Part 2, midazolam probe cohort), excipients contained therein, benzodiazepines, or other drug or other allergy that, in the opinion of the investigator or Sponsor Medical Monitor, contraindicates participation in the study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

ViiV Healthcare

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

GSK Clinical Trials

Role: STUDY_DIRECTOR

ViiV Healthcare

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

GSK Investigational Site

Baltimore, Maryland, United States

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

US GSK Clinical Trials Call Center

Role: CONTACT

Phone: 877-379-3718

Email: [email protected]

EU GSK Clinical Trials Call Center

Role: CONTACT

Phone: +44 (0) 20 89904466

Email: [email protected]

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

US GSK Clinical Trials Call Center

Role: primary

EU GSK Clinical Trials Call Centre

Role: backup

References

Explore related publications, articles, or registry entries linked to this study.

Rogg L, Underwood M, Hanan N, Castillo-Mancilla JR, Kahl L, Halliday F, Ghita GL, Jeffrey JL, Byrne S, Onodera T, Horton J, Gartland M. Phase 1 Evaluation of VH4524184, a Third-Generation Integrase Strand Transfer Inhibitor With an Enhanced Resistance Profile. Clin Infect Dis. 2025 Mar 21:ciaf135. doi: 10.1093/cid/ciaf135. Online ahead of print.

Reference Type DERIVED
PMID: 40117383 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

218803

Identifier Type: -

Identifier Source: org_study_id