Clinical trial NCT06214052: VH4524184 Proof-of-Concept in Treatment-Naïve Adults Living With HIV-1
Official title: A Phase 2a, Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled, Study to Investigate the Antiviral Effect, Safety, Tolerability and Pharmacokinetics of VH4524184 in HIV-1 Infected Treatment Naïve Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Human immunodeficiency virus
Proof of concept
Antiviral Agents
Virus Diseases
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2024-01-19
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, tolerability, ability of VH4524184 when given alone to reduce the amount of HIV (viral load) in people with HIV-1 infection who have never received antiretroviral therapy (treatment-naïve). Data from this study will be used to decide how VH4524184 can be best included in a full-treatment regimen for HIV-1 in the future.


Eligibility criteria: Inclusion Criteria:

* Participant must be 18 to 65 years of age inclusive at the time of signing the informed consent.
* Participants who are overtly healthy (other than HIV infection) as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
* Positive HIV antibody test
* Documented HIV infection and Screening plasma HIV-1 RNA ≥ 3,000 copies/mL. A single repeat of this test is allowed within a single Screening period to determine eligibility.
* Screening CD4+ T-cell count ≥200 cells/mm3
* Treatment-naïve: No antiretrovirals (ARVs, in combination or monotherapy) received after the diagnosis of HIV-1 infection.
* HIV Pre-exposure or post-exposure prophylaxis: No prior use of any INSTI (including cabotegravir) for HIV pre-exposure or post-exposure prophylaxis.
* Body weight ≥50.0 kg (110 lbs.) for men and ≥45.0 kg (99 lbs) for women and BMI within the range 18.5-31.0 kg/m2 (inclusive - applies to males and females).
* A participant of childbearing potential must have a negative serum hCG test at screening, and negative urine hCG test at Day 1, before the first dose of study intervention.
* If a urine test cannot be confirmed as negative (e.g. ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
* The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease risk for inclusion of a female with an early undetected pregnancy.
* Capable of giving signed informed consent
* Participant must be willing and able to start standard-of-care ART as selected with the investigator on Study Day 10.

Exclusion Criteria:

* Participants with primary HIV infection. Any evidence of an active CDC Stage 3 disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy during the study. Untreated syphilis infection \[positive RPR at screen\] without documentation of treatment. Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia; or other localized malignancies
* Any pre-existing physical or mental condition which, in the opinion of the Investigator, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant.
* Any history of significant underlying psychiatric disorder, or a clinical assessment of suicidality based on the responses on the eCSSRS.
* Any history of major depressive disorder with or without suicidal features, or anxiety disorders, that required medical intervention (pharmacologic or not) such as hospitalization or other inpatient treatment and/or chronic (\>6 months) outpatient treatment.
* Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome or sudden cardiac death. Treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, interferons) or any agent with known anti-HIV activity (such as hydroxyurea or foscarnet) within 30 days of study drug administration.
* Past or intended use of over-the-counter or prescription medication including herbal medications within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to dosing. Specific medications listed in Section 6.9.1 may be allowed.
* Participants who require concomitant medications known to be associated with a prolonged QTc.
* Participants receiving any protocol-prohibited medication(s) and who are unwilling or unable to switch to an alternate medication).
* The participant has ever received an investigational HIV vaccine (immunotherapeutic or immunomodulatory).
* Exposure to an experimental drug or experimental vaccine within either 30 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of study intervention.
* Participation in the study would result in donation of blood in excess of 500 mL within 56 days.
* Exposure to more than four new investigational drugs or vaccines within 12 months prior to the first dosing day.
* Current enrollment or past participation 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 in any other clinical study involving an investigational study intervention or any other type of medical research.

Diagnostic Assessments

* Presence of HBsAg or HBcAb at screening
* Positive Hepatitis C antibody test result at Screening
* Positive Hepatitis C RNA test result at Screening.
* Creatinine clearance (eGFR) of \< 60 mL/min/1.73 m2 using CKD-EPI equation (2021).

Primary outcomes:
measure: Maximum Change from Baseline in logarithm in 10 base (log10) Plasma HIV-1 Ribonucleic Acid (RNA) Through Day 10
timeFrame: Baseline (Day 1) and up to Day 10
Secondary outcomes:
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to Day 38
measure: Number of Participants with AEs by severity
timeFrame: Up to Day 38
measure: Number of Participants with AEs Leading to Study Treatment Discontinuation
timeFrame: Up to Day 38
measure: Change from Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ASP) (International units per liter)
timeFrame: Baseline (Day 1) and up to Day 38
measure: Change from Baseline for Liver Panel Laboratory Parameters: Total bilirubin, Direct bilirubin (Micromoles per liter [umol/L])
timeFrame: Baseline (Day 1) and up to Day 38
measure: Change from Baseline for Liver Panel Laboratory Parameters: Albumin and Total Protein (Grams per liter [g/L])
timeFrame: Baseline (Day 1) and up to Day 38
measure: Percentage of Participants with Maximum Toxicity Grade Increase Relative to Baseline in liver panel laboratory parameters: ALT, AST, total bilirubin, direct bilirubin, alkaline phosphatase, albumin and total protein
timeFrame: Up to Day 38
measure: Maximum Observed Plasma Drug Concentration (Cmax) of VH4524184
timeFrame: Up to Day 10
measure: Time to Maximum Observed Plasma Drugs Concentration (tmax) of VH4524184
timeFrame: Up to Day 10
measure: Plasma Concentration of VH4524184 on Day 10
timeFrame: Day 10
measure: Correlation of VH4524184 PK Parameters with Maximum Plasma HIV-1 RNA change from baseline through Day 10
timeFrame: Baseline (Day 1) and up to Day 10
measure: Number of Participants with Treatment-emergent Genotypic Resistance
timeFrame: Baseline (Day 1), Day 10
measure: Number of Participants with Treatment-emergent Phenotypic Resistance
timeFrame: Baseline (Day 1), Day 10
measure: Change From Baseline in Cluster of Differentiation 4 (CD4+) T-cell Counts at Day 10
timeFrame: Baseline (Day 1), Day 10
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: West Hollywood
country: United States
facility: GSK Investigational Site
state: California
city: DeLand
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma De Bueno
country: Argentina
facility: GSK Investigational Site
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Quebec City
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Milano
country: Italy
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Elche Alicante
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Murcia
country: Spain
facility: GSK Investigational Site
city: Santander
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
Study officials:
References: