Clinical trial NCT06613685: Study of Oral Weekly GS-1720 and GS-4182 Compared With Biktarvy in People With HIV-1 Who Have Not Been Treated
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 Treatment-Naive 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: 2024-09-26
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 (an oral, long-acting integrase strand transfer inhibitor (INSTI)) and GS-4182 (a prodrug of Lenacapavir (LEN)); to compare the combination of GS-1720 and GS-4182 with the current standard-of-care treatment bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (Biktarvy), 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 in treatment-naive people with HIV-1 (PWH).

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

The primary objectives of this study are:

Phase 2: To evaluate the efficacy of oral weekly GS-1720 coadministered with GS-4182 versus continuing Biktarvy (BVY) in treatment-naive PWH at Week 24.

Phase 3: To evaluate the efficacy of oral weekly GS-1720/GS-4182 fixed-dose combination (FDC) tablet regimen versus continuing BVY in treatment-naive PWH at Week 48.


Eligibility criteria: Key Inclusion Criteria:

* HIV-1 RNA ≥ 500 copies/mL at screening.
* Antiretroviral (ARV) treatment-naive, except the use of oral pre-exposure prophylaxis (PrEP) or postexposure prophylaxis (PEP) with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or F/TAF, up to 1 month prior to screening.

Key Exclusion Criteria:

* Prior use of any long acting parenteral antiretrovirals (ARVs) such as monoclonal antibodies, broadly neutralizing antibodies targeting HIV-1, LEN, injectable cabotegravir (including oral cabotegravir lead-in), and/or injectable rilpivirine.
* Documented resistance to the integrase strand-transfer inhibitor class, specifically, resistance-associated mutations E92G/Q, G118R, F121Y, Y143C/H/R, S147G, Q148H/K/R, N155H/S, or R263K in the integrase gene.
* Any of the following laboratory values at screening:

  1. CD4 cell count \< 200 cells/mm3 at screening.
  2. Estimated glomerular filtrations arate \< 60 mL/min according to the Modification of Diet in Renal Disease formula.
  3. Hepatic transaminases (aspartate aminotransferase and alanine aminotransferase) \> 1.5 × upper limit of normal (ULN).
  4. Direct bilirubin \> 1.5 × ULN.
  5. Platelets count \< 50,000 cells/mm3.
  6. Hemoglobin \< 8.0 g/dL.
* Active or occult hepatitis B virus infection.
* Active hepatitis C virus infection.

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: Change From Baseline in log10 HIV-1 RNA at Week 12
timeFrame: Baseline, Week 12
measure: Phase 2: Change From Baseline in log10 HIV-1 RNA at Week 24
timeFrame: Baseline, Week 24
measure: Phase 2: Change From Baseline in log10 HIV-1 RNA at Week 48
timeFrame: Baseline, Week 48
measure: Phase 2: Change From Baseline in Clusters of Differentiation 4 (CD4) Cell Count at Week 12
timeFrame: Baseline, Week 12
measure: Phase 2: Change From Baseline in CD4 Cell Count at Week 24
timeFrame: Baseline, Week 24
measure: Phase 2: Change From Baseline in CD4 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), as Applicable
timeFrame: Day 1 up to Week 24
measure: Phase 2: PK Parameter: Tmax of GS-1720 and LEN, as Applicable
timeFrame: Day 1 up to Week 24
measure: Phase 2: PK Parameter: Ctau of GS-1720 and LEN, as Applicable
timeFrame: Day 1 up to Week 24
measure: Phase 2: PK Parameter: AUCtau of GS-1720 and LEN, as Applicable
timeFrame: Day 1 up to Week 24
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 log10 HIV-1 RNA at Week 48
timeFrame: Baseline, Week 48
measure: Phase 3: Change From Baseline in log10 HIV-1 RNA at Week 96
timeFrame: Baseline, Week 96
measure: Phase 3: Change From Baseline in CD4 Cell Count at Week 48
timeFrame: Baseline, Week 48
measure: Phase 3: Change From Baseline in CD4 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: Percentage 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: Torrance
country: United States
facility: The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
state: California
city: West Hollywood
country: United States
facility: Mills Clinical Research
state: California
city: Washington
country: United States
facility: Georgetown University Medical School
state: District of Columbia
city: DeLand
country: United States
facility: Midland Florida Clinical Research Center, LLC
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center
state: Florida
city: Miami Lakes
country: United States
facility: Floridian Clinical Research, LLC
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute, P.A.
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital Midtown Infectious Disease Clinic
state: Georgia
city: Macon
country: United States
facility: Mercer University, Department of Internal Medicine
state: Georgia
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Newark
country: United States
facility: Saint Michael's Medical Center
state: New Jersey
city: New York
country: United States
facility: NYU Langone Health Vaccine Center
state: New York
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC) Research Nexus
state: South Carolina
city: Bellaire
country: United States
facility: St Hope Foundation, Inc.
state: Texas
city: Dallas
country: United States
facility: Prism Health North Texas, Aids Arms
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Diseases Consultants, PA
state: Texas
city: Fort Worth
country: United States
facility: Texas Centers for Infectious Disease Associates
state: Texas
city: San Antonio
country: United States
facility: UT Health San Antonio
state: Texas
city: Spokane
country: United States
facility: MultiCare Rockwood Main Clinic
state: Washington
city: Montreal
country: Canada
facility: Clinique Médicale L'Actuel
city: Montreal
country: Canada
facility: Chronic Viral Illness Service / McGill University Health Centre
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik I, Immunologische Studienambulanz
city: Essen
country: Germany
facility: Universitätsmedizin Essen, Universitätsklinikum Essen, Klinik für Dermatologie, Venerologie und Allergologie, HPSTD-Ambulanz
city: Hamburg
country: Germany
facility: ICH Study Center GmbH & Co. KG
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, Klinik für Rheumatologie und Immunologie, Gebäude K14
city: Munchen
country: Germany
facility: Klinikum rechts der Isar, Technische Universität München, Klinik und Poliklinik für Innere Medizin II
city: Bydoszcz
country: Poland
facility: Wojewódzki Szpital Obserwacyjno-Zakaźny im. Tadeusza Browicza
city: Gdansk
country: Poland
facility: Punkt Zdrowia
city: Szczecin
country: Poland
facility: Samodzielny Publiczny Wojewódzki Szpital Zespolony w Szczecinie
city: Amadora
country: Portugal
facility: Unidade Local de Saude de Amadora Sinatra EPE, Hospital Prof. Doutor Fernando Fonseca
city: Lisboa
country: Portugal
facility: Unidade Local de Saúde de Lisboa Ocidental E.P.E. - Hospital Egas Moniz
city: Lisboa
country: Portugal
facility: Unidade Local de Saúde de Santo Maria E.P.E. - Hospital Santa Maria
city: Porto
country: Portugal
facility: Unidade Local de Saúde de Santo António, E.P.E.
city: Porto
country: Portugal
facility: Unidade Local de Saúde de São João E.P.E.
city: San Juan
country: Puerto Rico
facility: HOPE Clinical Research
city: San Juan
country: Puerto Rico
facility: Proyecto ACTU
city: Bucharest
country: Romania
facility: Institutul National De Boli Infectioase Prof. Dr. Matei Bals
city: Bucharest
country: Romania
facility: Spitalul Clinic De Urgenta Prof Dr Agrippa Ionescu
city: Cluj-Napoca
country: Romania
facility: Spitalul Clinic De Boli Infectioase Cluj-Napoca
city: Constanta
country: Romania
facility: Spitalul Clinic de Boli Infectioase Constanta
city: Timisoara
country: Romania
facility: Clinical Hospital of Infectious Diseases and Pneumophysiology Dr. Victor Babes Timisoara
city: Bloemfontein
country: South Africa
facility: JOSHA Research
city: Durban
country: South Africa
facility: Durban International Clinical Research Site, Enhancing Care Foundation
city: East London
country: South Africa
facility: Synergy Biomed Research Institute
city: Germiston
country: South Africa
facility: CRISMO Research Center
city: Johannesburg
country: South Africa
facility: WITS RHI Research Centre
city: KwaZulu-Natal
country: South Africa
facility: Clinical Research Institute of South Africa (CRISA)
city: Ndevana
country: South Africa
facility: FPD Ndevana Community Research Site
city: Tembisa
country: South Africa
facility: The Aurum Institute Tembisa Clinic 4
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Pontevedra
country: Spain
facility: Hospital Universitario Alvaro Cunqueiro
city: Valencia
country: Spain
facility: Hospital Arnau de Vilanova de Valencia
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: