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

Overseen By US GSK Clinical Trials Call Center

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: ViiV Healthcare

Must not be taking: Over-the-counter, Prescription, Benzodiazepines, others

Disqualifiers: Gastro-intestinal disorders, Liver disease, Cardiac disease, Psychiatric condition, others

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on understanding the safety and metabolism of a new treatment called VH4524184. Researchers aim to determine if this treatment affects an enzyme called CYP3A, which helps break down drugs in the body. Participants will receive either VH4524184 or a placebo (a substance with no active drug). The trial suits healthy individuals without conditions affecting drug absorption and who haven't recently used certain medications or substances. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Do I have to stop taking my current medications for this trial?

Yes, you must stop taking any over-the-counter or prescription medications at least 7 days (or 14 days if the drug is a potential enzyme inducer) before the trial and for the duration of the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that VH4524184 is generally safe for humans. In early tests, most participants experienced no serious side effects, indicating a good safety profile. VH4524184 also does not appear to interfere with CYP3A4, an enzyme that breaks down many medications in the body, which is a positive sign for its safety. Although more research is needed, these early results are encouraging for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about VH4524184 because it offers a fresh approach to modifying cytochrome P450 3A (CYP3A) activity, a key player in drug metabolism. Unlike many existing treatments that target specific conditions, VH4524184 is being investigated for its potential to influence how the body processes various medications, possibly improving the effectiveness or safety of current drugs. This new mechanism of action could lead to more personalized and efficient treatment regimens, potentially reducing side effects and enhancing therapeutic outcomes.

What evidence suggests that this trial's treatments could be effective?

Research has shown that VH4524184, one of the investigational treatments in this trial, has promising effects against viruses. Studies have found that this new antiretroviral medication remains effective against HIV. Early results suggest it could match the strength of the best HIV drugs available today. It has also proven to be safe and well-tolerated, meaning most people can take it without serious side effects. This treatment might work longer with fewer doses needed. Participants in this trial may receive VH4524184 or a placebo, depending on their assigned cohort. ^{2 4 5 6 7}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

ViiV Healthcare

Are You a Good Fit for This Trial?

Inclusion Criteria

You have a body mass index (BMI) of at least 18.5 to 32.0 kg/m^2 (inclusive).

Participants who are overtly healthy.

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

You have a history of seizures.

Any positive (abnormal) response to the Columbia Suicide Severity Rating Scale (CSSRS)

You have a mental health condition like depression, anxiety, or trouble sleeping.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive single and multiple ascending doses of VH4524184 or placebo across different cohorts to investigate safety, tolerability, and pharmacokinetics

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Midazolam
• Placebo
• VH4524184

How Is the Trial Designed?

Group I: Part 3: Cohort 10: VH4524184 Fasted/ VH4524184 Fed Experimental Treatment 1 Intervention

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 II: Part 2: Cohort 9: Participants receiving VH4524184 RL3 Experimental Treatment 2 Interventions

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 III: Part 2: Cohort 8: Participants receiving VH4524184 RL2 Experimental Treatment 2 Interventions

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 IV: Part 2: Cohort 7: Participants receiving VH4524184 RL1 Experimental Treatment 1 Intervention

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

Group V: Part 1: Cohort 6: Participants receiving VH4524184 DL6 Experimental Treatment 1 Intervention

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

Group VI: Part 1: Cohort 5: Participants receiving VH4524184 DL5 Experimental Treatment 1 Intervention

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

Group VII: Part 1: Cohort 4: Participants receiving VH4524184 DL4 Experimental Treatment 1 Intervention

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

Group VIII: Part 1: Cohort 3: Participants receiving VH4524184 DL3 Experimental Treatment 1 Intervention

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

Group IX: Part 1: Cohort 2: Participants receiving VH4524184 DL2 Experimental Treatment 1 Intervention

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

Group X: Part 1: Cohort 1: Participants receiving VH4524184 DL1 Experimental Treatment 1 Intervention

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

Group XI: Part 2: Cohort 9: Participants receiving Placebo Placebo Group 2 Interventions

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 XII: Part 1: Cohort 1: Participants receiving Placebo Placebo Group 1 Intervention

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

Group XIII: Part 1: Cohort 4: Participants receiving Placebo Placebo Group 1 Intervention

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

Group XIV: Part 1: Cohort 6: Participants receiving Placebo Placebo Group 1 Intervention

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

Group XV: Part 1: Cohort 5: Participants receiving Placebo Placebo Group 1 Intervention

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

Group XVI: Part 1: Cohort 2: Participants receiving Placebo Placebo Group 1 Intervention

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

Group XVII: Part 2: Cohort 7: Participants receiving Placebo Placebo Group 1 Intervention

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

Group XVIII: Part 2: Cohort 8: Participants receiving Placebo Placebo Group 2 Interventions

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 XIX: Part 1: Cohort 3: Participants receiving Placebo Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

ViiV Healthcare

Lead Sponsor

Trials

379

Recruited

479,000+

Founded

2009

Headquarters

London, England, UK

Known For

HIV Research

Top Products

- Tivicay (dolutegravir), - Triumeq (abacavir/dolutegravir/lamivudine), - Juluca (dolutegravir/rilpivirine), - Apretude (cabotegravir)

Dr. Harmony Garges

ViiV Healthcare

Chief Medical Officer

MD

Deborah Waterhouse

ViiV Healthcare

Chief Executive Officer since 2017

Bachelor's degree in Business Administration

Published Research Related to This Trial

In a study involving 100 patients undergoing lumbar spine fusion surgeries, batroxobin and its combination with tranexamic acid significantly reduced both intraoperative and postoperative blood loss compared to a placebo.

The mean intraoperative blood loss was lowest in the batroxobin group (268.32 mL) and the combination group (256.96 mL), indicating their effectiveness, while no significant differences were found in blood transfusion needs or complications like deep vein thrombosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Batroxobin, Tranexamic Acid and a Combination in Reduction of Blood Loss in Lumbar Spinal Fusion Surgery. Nagabhushan, RM., Shetty, AP., Dumpa, SR., et al.[2021]

In a study involving six competitive wheelchair athletes, short-term oral creatine supplementation did not significantly improve 800 m performance compared to a placebo, indicating that creatine may not enhance performance in this specific group.

All measured parameters, including completion time, perceived exertion, lactate levels, and heart rate, showed no significant differences between the creatine and placebo conditions, suggesting that creatine supplementation may not be effective for trained, spinal cord-injured athletes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of creatine supplementation on 800 m wheelchair performance: a pilot study. Perret, C., Mueller, G., Knecht, H.[2013]

Citations

1. academic.oup.com academic.oup.com/cid/article/81/3/510/8090171

Phase 1 Evaluation of VH4524184, a Third-Generation ... VH4524184 does not inhibit/induce CYP3A4, has a moderate food effect, and demonstrated a good safety and tolerability profile in this first-time-in-human s.

2. viivhealthcare.com viivhealthcare.com/hiv-news-and-media/news/press-releases/2024/july/viiv-healthcare-premieres-early-data-showing-antiviral-activity/

ViiV Healthcare premieres early data showing antiviral ... An investigational integrase strand transfer inhibitor (INSTI), VH4524184 (VH184), retained its antiviral activity and could be effective in countering second- ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07202546

A Phase 2b Study Evaluating Oral VH4524184 Regimens ... The purpose of the study is to provide data on the long-term antiviral activity of the VH4524184 and provide information regarding dosing ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40117383/

Phase 1 Evaluation of VH4524184, a Third-Generation ... Conclusions: These data support the safety and further development of VH-184 as a third-generation INSTI with long-acting potential for HIV ...

5. aidsmap.com aidsmap.com/news/mar-2025/new-long-acting-hiv-drugs-show-promising-early-results

New long-acting HIV drugs show promising early results Two new long-acting antiretroviral drugs, VH-184 and VH-499, have demonstrated similar potency to the best available antiretrovirals currently in use in phase ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06214052

VH4524184 Proof-of-Concept in Treatment-Naïve Adults ... This study evaluates VH4524184's safety and ability to reduce HIV viral load in treatment-naïve adults, using a Phase 2a, randomized, double-blind design.

7. medinfo.gsk.com medinfo.gsk.com/5f95dbd7-245e-4e65-9f36-1a99e28e5bba/3ec67b86-3fd3-45d8-91e7-60eb9eb1cd44/3ec67b86-3fd3-45d8-91e7-60eb9eb1cd44_viewable_rendition__v.pdf

Phase 1 Study of VH4524184 (VH-184), a New Third- ... • These data support the further development of VH-184 ... • VH-184 demonstrated a good safety and tolerability profile in this FTIH study.