A Phase 2b Study Evaluating Oral VH4524184 Regimens in Treatment Naïve Persons With HIV-1 (INNOVATE Study)

Official title

A Phase 2b Randomized, Open-Label Active Controlled Study Evaluating the Safety and Efficacy of Oral VH4524184 Coadministered With Emtricitabine and Tenofovir Alafenamide in Treatment Naive Viremic Persons With HIV-1 (INNOVATE Study)

Overview

This clinical study is testing a new medication, VH4524184, to see if it can effectively treat HIV-1 in adults who have never received treatment for their infection. The study is comparing two different doses of VH4524184, each taken with the medications emtricitabine and tenofovir alafenamide (FTC/TAF), to a standard HIV treatment called dolutegravir and lamivudine (DTG/3TC). The purpose of the study is to provide data on the long-term antiviral activity of the VH4524184 and provide information regarding dosing formulation for further evaluations.

Interventions

• Drug VH4524184
  Oral tablet will be administered.
• Drug Emtricitabine (FTC) and tenofovir alafenamide (TAF) Fixed Dose Combination (FDC) tablets
  Oral table will be administered.
• Drug Dolutegravir / Lamivudine (DTG/3TC)
  Oral tablets will be administered.

Primary outcome measures

• Percentage of Participants Achieving Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) Suppression (<50 copies/millilitre) as per FDA Snapshot Methodology [Time frame: At Month 12]

Secondary outcome measures (7)

• Percentage of Participants Maintaining Plasma HIV-1 RNA Suppression (<50 copies/mL) Based on Observed Laboratory Results [Time frame: Day 1 to Month 24]
• Percentage of Participants Achieving Plasma HIV-1 RNA Suppression (<50 copies/ml) as per FDA Snapshot Methodology [Time frame: Day 1 to Month 24]
• Change From Baseline in Cluster of Differentiation 4 (CD4+) T-cell Counts [Time frame: Day 1 to Month 24]
• Number of Participants with Any Adverse Event (AE) [Time frame: Day 1 through the continuation period/end of study (approximately Month 36)]
• Number of Participants with AEs by Severity [Time frame: Day 1 through the continuation period/end of study (approximately Month 36)]
• Number of Participants with AEs Leading to Study Treatment Discontinuation [Time frame: Day 1 through the continuation period/end of study (approximately Month 36)]
• Plasma Concentration of VH4524184 [Time frame: Day 1 to Month 24]

Eligibility criteria

Inclusion criteria

• Participant must be at least 18 years of age (or older, if required for adults by local regulations) at the time of signing the informed consent.
• Screening CD4+ T-cell count >200 cells/microlitre (µL).
• Documented HIV-1 infection and Screening plasma HIV-1 RNA of ≥1000 copies/millilitre (mL). A single repeat of this test is allowed within a single Screening period to determine eligibility.
• Treatment-naive: Defined as no ARVs (in combination or monotherapy) received after the diagnosis of HIV-1 infection.
• Body weight >=50.0 kilogram (kg) \[(110 pounds (lbs)\] for participants assigned male at birth and >=45.0 kg (99 lbs) for participants assigned female at birth. BMI within the range 18.5-35.5 kg/m\^2 (inclusive - applies to males and females).
• There are no contraceptive requirements for participants assigned male at birth.
• Participants assigned female at birth are eligible to participate if they are not pregnant or breastfeeding and one of the following conditions applies:

• Is a Participant of non-childbearing potential (PONCBP);OR Is a Participant of childbearing potential (POCBP) and using a contraceptive method with a failure rate of less than (<) 1% prior to and during the study intervention period, and for at least 1 week after the last dose of VH4524184 plus FTC/TAF FDC, or through the end of study (if in the control arm and never received VH4524184).
• A POCBP must have a negative pregnancy test at Screening (serum) and on Day 1 (urine) before the first dose of study intervention.
• If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. Participant with a positive serum test must be excluded.
• Capable of giving signed informed consent. Persons who are placed in an institution by order of a public authority or a court are excluded from participation in this study.

Exclusion criteria

• Participants who are breastfeeding or plan to breastfeed during the study.
• Participants with acute HIV infection, evidenced by acute retroviral syndrome (e.g., fever, malaise, fatigue, etc.) and/or evidence of recent (within 3 months) documented viremia without antibody production and/or evidence of recent (within 3 months) documented seroconversion.
• Any evidence of an active Centres for Disease Control and Prevention (CDC) Stage 3 disease \[CDC 2014\], except cutaneous Kaposi's sarcoma not requiring systemic therapy during the study. Historical CD4+ cell counts less than 200 cells/µL are not exclusionary.
• Unstable liver disease known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment).
• History of cirrhosis with or without viral hepatitis co-infection.
• Participants with HCV co-infection will be excluded from the study.
• Individuals who are co-infected with HIV and HBV will be excluded Participants diagnosed with syphilis at Screening (i.e., positive syphilis testing) should be treated as per local guidelines and will be eligible to enroll at any time regardless of the stage of disease.
• Uncontrolled malignancy is excluded, whereas participants who have controlled malignancies may be included in agreement between the investigator and the ViiV Healthcare medical monitor.
• Any pre-existing physical, or mental condition (including alcohol or drug abuse) which, in the opinion of the investigator (with or without psychiatric evaluation) or the ViiV Healthcare medical monitor, 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 condition which, in the opinion of the investigator or the ViiV Healthcare medical monitor, that may interfere with the absorption, distribution, metabolism or excretion of the study interventions or render the participant unable to take oral medication and normal gastrointestinal anatomy or motility or hepatic and/or renal function
• Clinically significant CV disease, as defined by history/evidence of congestive heart failure, symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting surgery or percutaneous transluminal coronary angioplasty or any clinically significant cardiac disease.
• Participants receiving any protocol-prohibited medication and who are unwilling or unable to switch to an alternate medication.
• History of sensitivity to any of the study medications, or their components or drugs of their class, or a history of drug or other allergy that, in the opinion of the investigator or ViiV Healthcare medical monitor, contraindicates their participation.
• Current or anticipated need for chronic anti-coagulation with the exception of the use of low dose acetylsalicylic acid (≤325 mg) or hereditary coagulation and platelet disorders such as hemophilia or Von Willebrand Disease.
• Treatment with any of the following agents within 60 days of Screening: radiation therapy, cytotoxic chemotherapeutic agents, any systemic immune suppressant.
• 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 Day 1.
• Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.
• Exposure to an approved vaccine within 14 days prior to Day 1.
• Current enrollment or past participation within the last 30 days before signing of consent in any other clinical study involving an investigational study intervention or any other type of medical research
• Participants with known or suspected presence of virologic resistance mutations as defined by the Stanford HIV Drug Resistance Database to INSTIs or NRTIs. This determination will be based on local virologic resistance testing, either at Screening or within the 3 months prior to Screening. ViiV Healthcare clinical virologist and/or ViiV Healthcare medical monitor will verify eligibility to this criterion prior to Day 1.
• Creatinine clearance (eGFR) of <60 mL/min/1.73 m2 via CKD-EPI race neutral method \[Delgado, 2021\].
• ALT >3 times the upper limit of normal (ULN). A single repeat of ALT is allowed within a single screening period to determine eligibility.
• Any Grade 4 laboratory abnormality at screening, except for a Grade 4 CPK and lipid abnormalities (e.g., total cholesterol, triglycerides, etc.) will exclude a participant from the study unless the investigator can provide a compelling explanation for the laboratory result(s) and has the assent of the ViiV Healthcare medical monitor. A single repeat of any lab abnormality is allowed within a single screening period to determine eligibility.
• Any acute laboratory abnormality at screening which, in the opinion of the investigator, should preclude participation in the study of an investigational compound.
• Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination and will be the screening ECG entered into the eCRF): QT interval corrected for heart rate according to Fridericia's formula (QTcF) >450 msec (males) or >470 msec (females); >480 msec for participants with bundle branch block.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 35 centers

• GSK Investigational Site — Bakersfield
• GSK Investigational Site — Palm Springs
• GSK Investigational Site — West Hollywood
• GSK Investigational Site — Aurora
• GSK Investigational Site — New Haven
• GSK Investigational Site — Ft. Pierce
• GSK Investigational Site — Hollywood
• GSK Investigational Site — Miami
• … and 27 more centers

Spain · 34 centers

Center list to be confirmed — check the primary protocol.

Japan · 8 centers

• GSK Investigational Site — Fukuoka
• GSK Investigational Site — Kanagawa
• GSK Investigational Site — Okinawa
• GSK Investigational Site — Osaka
• GSK Investigational Site — Osaka
• GSK Investigational Site — Tokyo
• GSK Investigational Site — Tokyo
• GSK Investigational Site — Tokyo

Argentina · 7 centers

• GSK Investigational Site — Buenos Aires
• GSK Investigational Site — Buenos Aires
• GSK Investigational Site — Buenos Aires
• GSK Investigational Site — Ciudad Autonoma Buenos Aires
• GSK Investigational Site — Ciudad Autonoma de Bueno
• GSK Investigational Site — Mar del Plata
• GSK Investigational Site — San Miguel de Tucumán

Italy · 7 centers

• GSK Investigational Site — Bergamo
• GSK Investigational Site — Milan
• GSK Investigational Site — Milan
• GSK Investigational Site — Milan
• GSK Investigational Site — Milan
• GSK Investigational Site — Roma
• GSK Investigational Site — Roma

France · 6 centers

• GSK Investigational Site — Bordeaux
• GSK Investigational Site — Caen
• GSK Investigational Site — Nantes
• GSK Investigational Site — Nîmes
• GSK Investigational Site — Paris
• GSK Investigational Site — Paris

Germany · 5 centers

• GSK Investigational Site — Berlin
• GSK Investigational Site — Cologne
• GSK Investigational Site — Frankfurt
• GSK Investigational Site — Hamburg
• GSK Investigational Site — München

South Korea · 4 centers

Center list to be confirmed — check the primary protocol.

Taiwan · 4 centers

Center list to be confirmed — check the primary protocol.

Australia · 3 centers

• GSK Investigational Site — Sydney
• GSK Investigational Site — Clayton
• GSK Investigational Site — Melbourne

Belgium · 3 centers

• GSK Investigational Site — Antwerp
• GSK Investigational Site — Brussels
• GSK Investigational Site — Ghent

Portugal · 3 centers

• GSK Investigational Site — Porto
• GSK Investigational Site — Porto
• … and 1 more center

Canada · 2 centers

• GSK Investigational Site — Montreal
• GSK Investigational Site — Montreal

Poland · 2 centers

• GSK Investigational Site — Bydgoszcz
• GSK Investigational Site — Gdansk

Identifiers

NCT: NCT07202546 · 222638 · 2025-521918-26-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗