Clinical trial NCT06544733: Study of Oral Weekly GS-1720 and GS-4182 Versus Biktarvy in People With HIV-1 Who Are Virologically Suppressed
Official title: An Operationally Seamless Phase 2/3, Randomized, Active-Controlled Study Evaluating the Safety and Efficacy of an Oral Weekly Regimen of GS-1720 in Combination With GS-4182 Versus Biktarvy in Virologically Suppressed People With HIV-1
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: HIV-1-Infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2024-08-09
Enrollment: 675
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical study is to learn more about the experimental drugs GS-1720 and GS-4182; to compare the combination of GS-1720 and GS-4182 with the current standard-of-care treatment bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, BVY), to see if the combination of GS-1720 and GS-4182 is safe and if it works for treating human immunodeficiency virus type 1 (HIV-1) infection.

This study has two phases: Phase 2 and Phase 3.

The primary objectives of this study are:

Phase 2: To evaluate the efficacy of switching to oral weekly GS-1720 in combination with GS-4182 versus continuing BVY in virologically suppressed people with HIV-1 (PWH) at Week 24.

Phase 3: To evaluate the efficacy of switching to oral weekly GS-1720/GS-4182 Fixed-dose combination (FDC) tablet regimen versus continuing BVY in virologically suppressed PWH at Week 48.


Eligibility criteria: Key Inclusion Criteria:

* Documented plasma HIV-1 RNA \< 50 copies/mL for ≥ 24 weeks before and at screening.
* Receiving BVY for ≥ 24 weeks prior to screening.

Key Exclusion Criteria:

* Prior use of, or exposure to LEN, GS-1720, or GS-4182.
* History of virologic failure while on an integrase strand-transfer inhibitor (INSTI)-based regimen.
* Documented integrase strand-transfer inhibitor (INSTI) resistance, specifically, resistance-associated mutations (RAMs) E92G/Q, G118R, F121Y, Y143C/H/R, S147G, Q148H/K/R, N155H/S, or R263K in the integrase gene.
* Prior use of any long-acting (LA) parenteral antiretrovirals (ARV) such as monoclonal antibodies (mAbs) or broadly neutralizing antibodies (bNAbs) targeting HIV-1, injectable cabotegravir (including oral cabotegravir lead-in), or injectable rilpivirine.
* Any of the following laboratory values at screening:

  * Clusters of differentiation 4 (CD4) cell count \< 200 cells/mm\^3 at screening
  * Glomerular filtration rate \< 60 mL/min according to the Modification of Diet in Renal Disease formula
  * Hepatic transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \> 1.5 × upper limit of normal (ULN)
  * Direct bilirubin \> 1.5 × ULN
  * Platelets count \< 50,000 cells/mm\^3
  * Hemoglobin \< 8.0 g/dL
* Active or occult hepatitis B virus (HBV) infection.
* Active hepatitis C virus (HCV).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Phase 2: Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 24 as Determined by the United States (US) Food and Drug Administration (FDA)-defined Snapshot Algorithm
timeFrame: Week 24
measure: Phase 3: Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm
timeFrame: Week 48
Secondary outcomes:
measure: Phase 2: Proportion of Participants With HIV-1 RNA ≥ 50 copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm
timeFrame: Week 12
measure: Phase 2: Proportion of Participants With HIV-1 RNA ≥ 50 copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm
timeFrame: Week 48
measure: Phase 2: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm
timeFrame: Week 12
measure: Phase 2: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm
timeFrame: Week 24
measure: Phase 2: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm
timeFrame: Week 48
measure: Phase 2: Change From Baseline in Clusters of Differentiation 4 (CD4+) T-cell Count at Week 12
timeFrame: Baseline, Week 12
measure: Phase 2: Change From Baseline in CD4+ T-cell Count at Week 24
timeFrame: Baseline, Week 24
measure: Phase 2: Change From Baseline in CD4+ T-cell Count at Week 48
timeFrame: Baseline, Week 48
measure: Phase 2: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) Through Week 12
timeFrame: First dose date up to Week 12
measure: Phase 2: Percentage of Participants Experiencing TEAEs Through Week 24
timeFrame: First dose date up to Week 24
measure: Phase 2: Percentage of Participants Experiencing TEAEs Through Week 48
timeFrame: First dose date up to Week 48
measure: Phase 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 12
timeFrame: First dose date up to Week 12
measure: Phase 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 24
timeFrame: First dose date up to Week 24
measure: Phase 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 48
timeFrame: First dose date up to Week 48
measure: Phase 2: Pharmacokinetic (PK) Parameter: Cmax of GS-1720 and Lenacapavir (LEN)
timeFrame: Day 1 up to Week 48
measure: Phase 2: PK Parameter: Tmax of GS-1720 and LEN
timeFrame: Day 1 up to Week 48
measure: Phase 2: PK Parameter: Ctau of GS-1720 and LEN
timeFrame: Day 1 up to Week 48
measure: Phase 2: PK Parameter: AUCtau of GS-1720 and LEN
timeFrame: Day 1 up to Week 48
measure: Phase 3: Proportion of Participants With HIV-1 RNA ≥ 50 copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm
timeFrame: Week 96
measure: Phase 3: Proportion of Participants With HIV-1 RNA < 50 copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm
timeFrame: Week 48
measure: Phase 3: Proportion of Participants With HIV-1 RNA < 50 copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm
timeFrame: Week 96
measure: Phase 3: Change From Baseline in CD4+ T-cell Count at Week 48
timeFrame: Baseline, Week 48
measure: Phase 3: Change From Baseline in CD4+ T-cell Count at Week 96
timeFrame: Baseline, Week 96
measure: Phase 3: Percentage of Participants Experiencing TEAEs Through Week 48
timeFrame: First dose date up to Week 48
measure: Phase 3: Proportion of Participants Experiencing TEAEs Through Week 96
timeFrame: First dose date up to Week 96
measure: Phase 3: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 48
timeFrame: First dose date up to Week 48
measure: Phase 3: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 96
timeFrame: First dose date up to Week 96
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB 1917 Research Clinic
state: Alabama
city: Beverly Hills
country: United States
facility: Pacific Oaks Medical Group
state: California
city: Los Angeles
country: United States
facility: Ruane Clinical Research Group
state: California
city: Los Angeles
country: United States
facility: Mills Clinical Research
state: California
city: Palm Springs
country: United States
facility: BIOS Clinical Research
state: California
city: San Francisco
country: United States
facility: UCSF Division of HIV, Infectious Diseases & Global Medicine
state: California
city: Torrance
country: United States
facility: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: DeLand
country: United States
facility: Midland Florida Clinical Research Center, LLC
state: Florida
city: Fort Lauderdale
country: United States
facility: CAN Community Health
state: Florida
city: Fort Pierce
country: United States
facility: Midway and Immunology Research Center
state: Florida
city: Miami Lakes
country: United States
facility: Floridian Clinical Research
state: Florida
city: Miami
country: United States
facility: AIDS Healthcare Foundation - The Kinder Medical Group
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Sarasota
country: United States
facility: CAN Community Health
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute, P.A.
state: Florida
city: Decatur
country: United States
facility: Metro Infectious Disease Consultants, P.L.L.C.
state: Georgia
city: Macon
country: United States
facility: Mercer University, Department of Internal Medicine
state: Georgia
city: Savannah
country: United States
facility: Chatham County Health Department
state: Georgia
city: Berkley
country: United States
facility: Be Well Medical Center
state: Michigan
city: Kansas City
country: United States
facility: KC CARE Health Center
state: Missouri
city: Newark
country: United States
facility: Saint Michael's Medical Center
state: New Jersey
city: Santa Fe
country: United States
facility: AXCES Research Group, LLC
state: New Mexico
city: Flushing
country: United States
facility: NewYork-Presbyterian Queens
state: New York
city: New York
country: United States
facility: NYU Langone Health Vaccine Center
state: New York
city: Huntersville
country: United States
facility: Rosedale Health and Wellness
state: North Carolina
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Bellaire
country: United States
facility: St Hope Foundation, Inc.
state: Texas
city: Dallas
country: United States
facility: Prism Health North Texas, Oak Cliff Health Center
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Diseases Consultants, PA
state: Texas
city: El Paso
country: United States
facility: AXCES Research Group, LLC
state: Texas
city: Fort Worth
country: United States
facility: Texas Centers for Infectious Disease Associates
state: Texas
city: Houston
country: United States
facility: The Crofoot Research Center, INC.
state: Texas
city: Longview
country: United States
facility: DCOL Center for Clinical Research
state: Texas
city: Seattle
country: United States
facility: Peter Shalit, MD
state: Washington
city: San Juan
country: Puerto Rico
facility: Centro Ararat, Inc.
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico
city: San Juan
country: Puerto Rico
facility: HOPE Clinical Research
city: San Juan
country: Puerto Rico
facility: Proyecto ACTC
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: