VH4524184 Proof-of-Concept in Treatment-Naïve Adults Living With HIV-1

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06214052
• Other study ID #: 218806
• Secondary ID: 2023-507173-18-0
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: February 14, 2024
• Est. completion date: September 16, 2024

Study information

• Verified date: February 2024
• Source: ViiV Healthcare
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 28
• Est. completion date: September 16, 2024
• Est. primary completion date: September 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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).

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• VH4524184
VH4524184 will be administered.
• Placebo
Placebo will be administered.

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Almagro	Caba
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires	Buenos Aires
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Québec
Canada	GSK Investigational Site	Toronto	Ontario
Italy	GSK Investigational Site	Milano
Italy	GSK Investigational Site	Monza
Italy	GSK Investigational Site	Padova	Veneto
Mexico	GSK Investigational Site	Chihuahua
Mexico	GSK Investigational Site	Mexico City
Mexico	GSK Investigational Site	San Pedro Garza García	Nuevo León
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Elche
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Murcia
Spain	GSK Investigational Site	Santander
Spain	GSK Investigational Site	Valencia
United States	GSK Investigational Site	Bakersfield	California
United States	GSK Investigational Site	DeLand	Florida
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Newark	New Jersey
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Palm Springs	California
United States	GSK Investigational Site	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
ViiV Healthcare	GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Italy,  Mexico,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Change from Baseline in logarithm in 10 base (log10) Plasma HIV-1 Ribonucleic Acid (RNA) Through Day 10	The antiviral activity of VH4524184 in treatment-naïve (TN) participants with HIV-1 during 10 days of monotherapy will be evaluated.	Baseline (Day 1) and up to Day 10
Secondary	Number of Participants with Adverse Events (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. An AE can be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to Day 38
Secondary	Number of Participants with AEs by severity		Up to Day 38
Secondary	Number of Participants with AEs Leading to Study Treatment Discontinuation		Up to Day 38
Secondary	Change from Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ASP) (International units per liter)		Baseline (Day 1) and up to Day 38
Secondary	Change from Baseline for Liver Panel Laboratory Parameters: Total bilirubin, Direct bilirubin (Micromoles per liter [umol/L])		Baseline (Day 1) and up to Day 38
Secondary	Change from Baseline for Liver Panel Laboratory Parameters: Albumin and Total Protein (Grams per liter [g/L])		Baseline (Day 1) and up to Day 38
Secondary	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		Up to Day 38
Secondary	Maximum Observed Plasma Drug Concentration (Cmax) of VH4524184	Blood samples will be collected at indicated time points for Pharmacokinetic (PK) analysis of VH4524184.	Up to Day 10
Secondary	Time to Maximum Observed Plasma Drugs Concentration (tmax) of VH4524184	Blood samples will be collected at indicated time points for PK analysis of VH4524184.	Up to Day 10
Secondary	Plasma Concentration of VH4524184 on Day 10	Blood samples will be collected at indicated time points for PK analysis of VH4524184.	Day 10
Secondary	Correlation of VH4524184 PK Parameters with Maximum Plasma HIV-1 RNA change from baseline through Day 10	Any relationship between VH4524184 exposure and change in plasma HIV-1 RNA will be evaluated.	Baseline (Day 1) and up to Day 10
Secondary	Number of Participants with Treatment-emergent Genotypic Resistance	Genotypic data from baseline (Day 1) and Day 10 will be compared to identify amino acid substitutions and assess the fold change in the half maximal inhibitory concentration (IC50) for VH4524184.	Baseline (Day 1), Day 10
Secondary	Number of Participants with Treatment-emergent Phenotypic Resistance	Phenotypic data from baseline (Day 1) and Day 10 will be compared to identify amino acid substitutions and assess the fold change in the half maximal inhibitory concentration (IC50) for VH4524184.	Baseline (Day 1), Day 10
Secondary	Change From Baseline in Cluster of Differentiation 4 (CD4+) T-cell Counts at Day 10	Immune response to VH452418 will be evaluated over 10 days in participants living with HIV. Blood samples will be collected for assessment of lymphocyte subsets (CD4+ lymphocyte count) by flow cytometry at Baseline and Day 10.	Baseline (Day 1), Day 10