VH4524184 / ViiV Healthcare, GSK, Shionogi - LARVOL DELTA

A Phase 2b Study Evaluating Oral VH4524184 Regimens in Treatment Naïve Persons With HIV-1 (INNOVATE Study) (clinicaltrials.gov) - P2 | N=550 | Not yet recruiting | Sponsor: ViiV Healthcare

New P2 trial • Human Immunodeficiency Virus • Infectious Disease

A Study to Evaluate VH4524184 Tablet Absorption, Effects of Food, and Interactions With Other Drugs in Healthy Adults (clinicaltrials.gov) - P1 | N=124 | Recruiting | Sponsor: ViiV Healthcare | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

A Study to Evaluate VH4524184 Tablet Absorption, Effects of Food, and Interactions With Other Drugs in Healthy Adults (clinicaltrials.gov) - P1 | N=124 | Not yet recruiting | Sponsor: ViiV Healthcare

New P1 trial • Human Immunodeficiency Virus • Infectious Disease

Phase 1 Evaluation of VH4524184, a Third-Generation Integrase Strand Transfer Inhibitor With an Enhanced Resistance Profile. (PubMed, Clin Infect Dis) - P1 | "These data support the safety and further development of VH-184 as a third-generation INSTI with long-acting potential for HIV-1 treatment (ClinicalTrials.gov, NCT05631704)."

Journal • P1 data • Human Immunodeficiency Virus • Infectious Disease

Proof-of-Concept Trial of VH4524184 (VH-184), a Third-Generation Integrase Strand Transfer Inhibitor (CROI 2025) - "An exposure-response relationship was established comparable to the maximum effect with other INSTIs. These results support further development of VH-184 as the core agent in a complete long-acting regimen for the treatment of HIV-1."

Human Immunodeficiency Virus • Infectious Disease

First Time in Human Study of Long Acting VH4524184 Formulations (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: ViiV Healthcare | Trial primary completion date: Mar 2027 ➔ Jan 2028

Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

A Study to Investigate the Potential Drug-Drug Interaction Between VH4524184 and Oral Contraceptive (Loestrin) in Healthy Adult Female Participants (clinicaltrials.gov) - P1 | N=26 | Completed | Sponsor: ViiV Healthcare | Recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

VH4524184 Proof-of-Concept in Treatment-Naïve Adults Living With HIV-1 (clinicaltrials.gov) - P2 | N=22 | Completed | Sponsor: ViiV Healthcare | Recruiting ➔ Completed | Trial completion date: Sep 2024 ➔ Jun 2024 | Trial primary completion date: Sep 2024 ➔ Jun 2024

Trial completion • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

Phase 1 study of VH4524184 (VH-184), a new third-generation integrase strand transfer inhibitor (INSTI) with a unique resistance profile (AIDS 2024) - "We present the pharmacokinetics, safety, and in vitro resistance profile of VH-184. A double-blind, randomized, placebo-controlled, phase 1, first-time-in-human (FTIH) study evaluated oral VH-184 in healthy adults administered as single ascending doses (10-460 mg; part 1), multiple ascending doses (160-480 mg) for 14 days with concomitant midazolam (part 2), and as a single dose (100 mg) under fasted and fed conditions (part 3)...VH-184 demonstrated potent in vitro antiviral activity against dolutegravir-selected INSTI-resistant isolates (Figure). FTIH study results helped characterize VH-184 pharmacokinetics and indicate that VH-184 does not inhibit or induce CYP3A4 and has a moderate positive food effect. FTIH study results helped characterize VH-184 pharmacokinetics and indicate that VH-184 does not inhibit or induce CYP3A4 and has a moderate positive food effect. The in vitro resistance profile of VH-184 is distinct from prior INSTIs, retaining antiviral activity..."

P1 data • Human Immunodeficiency Virus • Infectious Disease • CYP3A4

In vitro characterization of VH4524184 (VH-184, S-365598), a new third-generation integrase strand transfer inhibitor (INSTI) with a unique resistance profile (AIDS 2024) - "The in vitro antiviral potency of VH-184 is comparable to DTG and CAB and its resistance profile is distinct from prior INSTIs. VH-184 is a third generation INSTI candidate with a superior resistance profile compared to DTG and CAB. These data support its further development for HIV-1 treatment."

Preclinical • Human Immunodeficiency Virus • Infectious Disease • CD4

First Time in Human Study of Long Acting VH4524184 Formulations (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: ViiV Healthcare | Not yet recruiting ➔ Recruiting | Trial completion date: Nov 2026 ➔ Jan 2028 | Trial primary completion date: Feb 2025 ➔ Mar 2027

Enrollment open • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

VH4524184 Proof-of-Concept in Treatment-Naïve Adults Living With HIV-1 (clinicaltrials.gov) - P2 | N=28 | Recruiting | Sponsor: ViiV Healthcare | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

A Study to Investigate the Potential Drug-Drug Interaction Between VH4524184 and Oral Contraceptive (Loestrin) in Healthy Adult Female Participants (clinicaltrials.gov) - P1 | N=25 | Recruiting | Sponsor: ViiV Healthcare

New P1 trial • Human Immunodeficiency Virus • Infectious Disease

First Time in Human Study of Long Acting VH4524184 Formulations (clinicaltrials.gov) - P1 | N=72 | Not yet recruiting | Sponsor: ViiV Healthcare

New P1 trial • Human Immunodeficiency Virus • Infectious Disease

VH4524184 Proof-of-Concept in Treatment-Naïve Adults Living With HIV-1 (clinicaltrials.gov) - P2 | N=28 | Not yet recruiting | Sponsor: ViiV Healthcare

New P2 trial • Human Immunodeficiency Virus • Infectious Disease

A Study to Investigate Safety, Tolerability, and Pharmacokinetics (PK) of VH4524184 and the Potential for Changes in Cytochrome P450 3A (CYP3A) Activity (clinicaltrials.gov) - P1 | N=105 | Recruiting | Sponsor: ViiV Healthcare | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

A Study to Investigate Safety, Tolerability, and Pharmacokinetics (PK) of VH4524184 and the Potential for Changes in Cytochrome P450 3A (CYP3A) Activity (clinicaltrials.gov) - P1 | N=105 | Not yet recruiting | Sponsor: ViiV Healthcare

New P1 trial • Human Immunodeficiency Virus • Infectious Disease