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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Viiv Healthcare UK Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

11 Feb 2026 → ongoing

Decision date (initial)

2026-04-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

ViiV Healthcare UK Ltd

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety

To evaluate the antiviral efficacy of oral VH4524184 containing regimens compared to DTG/3TC FDC oral control arm in treatment naïve viremic adults living with HIV-1

Secondary objectives 4

1. To further evaluate the antiviral efficacy of oral VH4524184 containing regimens compared to the DTG/3TC FDC oral control arm
2. To evaluate the immunologic effects of oral VH4524184 containing regimens compared to the DTG/3TC FDC oral control arm
3. To assess the safety and tolerability of oral VH4524184 containing regimens compared to the DTG/3TC FDC oral control arm
4. To assess the PK of VH4524184 during the Treatment Period

Conditions and MedDRA coding

HIV Infections

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

IPD plan description: Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data (IPD) and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.viiv-studyregister.com/documents/About_ViiV_Patient_Level_Data_Sharing_Final_25Sep2023.pdf IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months. IPD Sharing Time Frame:Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 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.
2. Screening CD4+ T-cell count greater than or equal to 200 cells/µL.
3. Documented HIV-1 infection and Screening plasma HIV-1 RNA of ≥1000 copies/mL. A single repeat of this test is allowed within a single Screening period to determine eligibility.
4. Treatment-naïve: Defined as no ARVs (in combination or monotherapy) received after the diagnosis of HIV-1 infection. The prior use of oral pre-exposure prophylaxis or oral post-exposure prophylaxis is permitted and meets inclusion. (Note: Prior use of LA CAB is exclusionary)
5. France: Participants enrolled in France must be affiliated with, or be a beneficiary of a social security system
6. Body weight greater than or equal to 50.0 kg (110 lbs) for participants assigned male at birth and greater than or equal to 45.0 kg (99 lbs) for participants assigned female at birth. BMI within the range 18.5-35.5 kg/m2 (inclusive - applies to males and females).
7. There are no contraceptive requirements for participants assigned male at birth.
8. Participants assigned female at birth are eligible to participate if they are not pregnant and not breastfeeding and one of the following conditions applies: • Is a PONCBP; OR • Is a POCBP and using a contraceptive method that is highly effective, with a failure rate of <1% (see Section 10.4.2) 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). The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention. - A POCBP must have a negative highly sensitive 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. 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 the risk for inclusion of an individual with an early undetected pregnancy.
9. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and stated in this protocol.

Exclusion criteria 29

1. Participants who are breastfeeding or plan to breastfeed during the study.
2. 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.
3. 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.
4. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening
5. Exposure to an investigational drug or experimental vaccine within either 28 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.
6. Exposure to an approved vaccine within 14 days prior to Day 1.
7. 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.
8. 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.
9. Creatinine clearance (eGFR) of <60 mL/min/1.73 m2 via CKD-EPI race neutral method [Delgado, 2021]. • Japan: For Japanese participants enrolled at sites in Japan, the eGFR will be calculated using the serum creatinine-based Japanese eGFR estimation formula (JSN eGFRcr) recommended by the Japanese Society of Nephrology [Japanese Society of Nephrology, 2024].
10. ALT > or = 3 times the ULN. A single repeat of ALT is allowed within a single screening period to determine eligibility.
11. 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.
12. Participants who in the investigator’s judgment, pose a significant suicidality risk. Participant’s history of suicidal behavior and/or suicidal ideation (as measured with the C-SSRS prior to dosing) should be considered when evaluating suicide risk.
13. Any acute laboratory abnormality at Screening which, in the opinion of the investigator, should preclude participation in the study of an investigational compound.
14. Any evidence of an active 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.
15. 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.
16. Unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice or cirrhosis), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment).
17. Known history of cirrhosis with or without viral hepatitis co-infection.
18. Participants with HCV co-infection will be excluded from the study.
19. Individuals who are co-infected with HIV and HBV will be excluded. Exclusion will be determined by evidence of HBV infection based on the results of testing at Screening for HBsAg, HBcAb, HBsAb and HBV DNA as follows: a. Participants positive for HBsAg are excluded; b. Participants negative for HBsAb and negative for HBsAg but positive for HBcAb may be excluded based on the following. Consideration: i. Exclude if HBV DNA is detected (either < LLOQ, > ULOQ OR numerical value [ie, between LLOQ and ULOQ]) ii. Not excluded if HBV DNA is negative, not detected Note: Participants positive for HBcAb, negative for HBsAg and positive for HBsAb (past and/or current evidence, e.g., at screening) are considered to be immune to HBV and are not excluded.
20. 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. When RPR or VDRL titers are high (i.e., ≥1:256), investigators should consider syphilis treatment before study enrollment, but may enroll 48 hours after treatment initiation.
21. Uncontrolled malignancy is excluded, whereas participants who have controlled malignancies may be included in agreement between the investigator and the ViiV Healthcare medical monitor.
22. 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.
23. Any condition which, in the opinion of the investigator or the ViiV Healthcare medical monitor, may interfere with the absorption, distribution, metabolism or excretion of the study interventions or render the participant unable to take oral medication.
24. A pre-existing condition, in the opinion of the investigator or ViiV Healthcare medical monitor, that could interfere with normal gastrointestinal anatomy or motility (e.g., gastroesophageal reflux disease, gastric ulcers, gastritis, inflammatory bowel disease) or hepatic and/or renal function
25. 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.
26. 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.
27. 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.
28. Treatment with any of the following agents within 60 days of Screening: radiation therapy, cytotoxic chemotherapeutic agents, any systemic immune suppressant.
29. Participants receiving any protocol-prohibited medication and who are unwilling or unable to switch to an alternate medication.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Plasma HIV-1 RNA <50 copies/mL (FDA snapshot) at Month 12

Secondary endpoints 4

1. • Plasma HIV-1 RNA <50 copies/mL (observed) until Month 24. • Plasma HIV-1 RNA <50 copies/mL (FDA snapshot) until Month 24.
2. Change from baseline in CD4+ T-cell count until Month 24.
3. To assess the safety and tolerability of oral VH4524184 containing regimens compared to the DTG/3TC FDC oral control arm
4. To assess the PK of VH4524184 during the Treatment Period

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Viiv Healthcare UK Limited

Sponsor organisation

Viiv Healthcare UK Limited

Address

79 New Oxford Street

City

London

Postcode

WC1A 1DG

Country

United Kingdom

Scientific contact point

Organisation

Viiv Healthcare UK Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Viiv Healthcare UK Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 13

Locations

7 EU/EEA countries · 78 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 194 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications