Viiv Phase 2b study evaluating oral VH4524184 regimens in treatment naïve persons with HIV-1 (INNOVATE Study)

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 (TN) 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.

The trial is aiming to enroll 550 participants starting in November 2025. Current PCD is June 11, 2027 and SCD is March 19, 2029.

The open-label, randomized study includes three experimental arms:

• The active comparator arm is QD oral DTG/3TC from day 1 to M24.
• Participants receive a QD oral ‘low dose’ of VH184 (Dose A), in combination with FTC/TAF from Day 1 through Month 12.
• Participants receive a QD oral ‘high dose’ of VH184 (Dose B), in combination with FTC/TAF from Day 1 through Month 12.
• Participants receive an oral QD ‘selected dose of VH184’ in combination with FTC/TAF from M12 to M24.

The primary outcome measure is percentage of participants achieving plasma HIV RNA suppression (<50 copies/mL) at M12.

• Secondary outcomes include additional efficacy, safety, and PK measures assessed through M24.

Inclusion criteria includes TN adults screening CD4+ T-cell count >200 cells/µL and plasma HIV-1 RNA of ≥1000 copies/mL.

Trial sites are yet to be disclosed.

Assessment:

This study was likely driven by the positive outcomes of ViiV’s Ph2a POC for oral VH184 in TN PWH (NCT06214052), which demonstrated high antiviral activity, a unique resistance profile, and tolerability.

• That data presented at CROI 2025, included 22 participants with BL HIV RNA ≥3000 c/mL and follow-up only through Day 38. This subsequent Ph2b study may be designed to generate more robust safety data, with a larger trial population (n=550), lower BL VL thresholds (HIV RNA >1000 copies/mL) and a longer trial duration. 

ViiV continues to tout VH184 as their “next-generation” INSTI and a potential asset for their Q6M and self-admin HIV treatment programs. ViiV continues to evaluate early LAI SC and IM formulations of VH184, and this trial could be used to help inform LAI development by derisking the safety of VH184 with a known asset ahead of future combinations.

• CI will continue to monitor for any additional updates on their clinical development program for VH184 including consideration as an oral asset.
• ViiV has noted VH184 patent expiry is 2039.