Study to Compare Bictegravir/Lenacapavir Versus Current Therapy in People With HIV-1 Who Are Successfully Treated With Biktarvy (ARTISTRY-2)

Phase 3 Double-blind Multicenter Randomized Active-Controlled Study to Evaluate the Safety and Efficacy of Bictegravir/Lenacapavir Versus Biktarvy® (Bictegravir/Emtricitabine/Tenofovir Alafenamide) in Virologically Suppressed People With HIV-1

The goal of this clinical study is to learn more about the effects of switching to the study drugs, bictegravir (BIC)/lenacapavir (LEN), fixed-dose combination (FDC) versus current therapy bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) FDC in people living with HIV-1 (PWH).

The primary objective of this study is to learn how effective it is to switch to BIC/LEN FDC tablets versus continuing on B/F/TAF FDC tablets in virologically suppressed PWH.

Study Overview

• Status: Recruiting
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: Bictegravir; Drug: Lenacapavir; Drug: B/F/TAF; Drug: Placebo to match B/F/TAF; Drug: Placebo to match BIC/LEN

• Study Type: Interventional
• Enrollment (Estimated): 546
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Gilead Clinical Study Information Center; Phone Number: 1-833-445-3230 (GILEAD-0); Email: GileadClinicalTrials@gilead.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90036
      • Recruiting
      • Ruane Medical and Clinical Research Institute
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Recruiting
      • Therafirst Medical Center
    • Fort Pierce, Florida, United States, 34982
      • Recruiting
      • Midway Immunology and Research Center
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Recruiting
      • Infectious Disease Specialists of Atlanta
  • Missouri
    • Saint Louis, Missouri, United States, 63139
      • Recruiting
      • Southhampton Community Healthcare, Inc.
  • New Jersey
    • Somers Point, New Jersey, United States, 08244
      • Recruiting
      • South Jersey Infectious Disease
  • Texas
    • Houston, Texas, United States, 77098
      • Recruiting
      • The Crofoot Research Center, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Currently receiving B/F/TAF for at least 6 months prior to screening.
• If plasma human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) measurements in the last 6 months prior to screening are available, all levels must be < 50 copies/mL.
• At least one documented HIV-1 RNA level measured between 6 and 12 months (± 2 months) prior to screening. This and any other HIV-1 RNA measurements documented in this period must be < 50 copies/mL.
• Plasma HIV-1 RNA levels < 50 copies/mL at screening.
• No documented or suspected resistance to BIC (including integrase strand-transfer inhibitor resistant (INSTI-R) mutations T66A/I/K, E92G/Q, G118R, F121Y, Y143C/H/R, S147G, Q148H/K/R, N155H/S, or R263K in the integrase gene).
• No documented or suspected resistance to tenofovir alafenamide (TAF) (TAF; mutations K65R, K65N, K70E, Q151M or T69 insertion, or ≥ 3 of the following thymidine analog mutations [M41L, D67N, K70R, L210W, T215Y/F, K219Q/E/N/R] in the reverse transcriptase gene).
• Estimated glomerular filtration rate ≥ 30 mL/min according to the Cockcroft-Gault formula for creatinine clearance.

Key Exclusion Criteria:

• Positive serum pregnancy test or pregnant at screening or a positive pregnancy test prior to Day 1 randomization.
• Breastfeeding (nursing).
• Prior use of, or exposure to, LEN.
• Active, serious infections (other than HIV-1) requiring parenteral therapy < 30 days prior to randomization.
• Active tuberculosis infection.
• Acute hepatitis < 30 days before randomization.

• Chronic hepatitis B virus (HBV) infection, as determined by either:

  • Positive HBV surface antigen and negative HBV surface antibody, regardless of HBV core antibody status, at the screening visit.
  • Positive HBV core antibody and negative HBV surface antibody, regardless of HBV surface antigen status, at the screening visit.
• Known hypersensitivity to the study drug, its metabolites, or any formulation excipient.
• History of or current clinical decompensated liver cirrhosis (eg, ascites, encephalopathy, or variceal bleeding).
• Abnormal electrocardiogram (ECG) at the screening visit that is clinically significant as determined by the investigator.
• Active malignancy requiring acute systemic therapy.

• Any of the following laboratory values at screening:

  • Alanine aminotransferase > 5 × upper limit of normal (ULN).
  • Direct bilirubin > 1.5 × ULN.
  • Platelets < 50,000/mm^3.
  • Hemoglobin < 8.0 g/dL.
• Requirement for ongoing therapy with or prior use of any prohibited medications listed in the protocol.
• Participation or planned participation in any other clinical study (including observational studies) without prior approval from the sponsor.
• Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the participant unsuitable for the study or unable to comply with dosing requirements.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group 1: Bictegravir (BIC)/ Lenacapavir (LEN) (75/50 mg) + PTM B/F/TAF; Blinded Phase: Participants will switch from bictegravir/emtricitabine/tenofovir (B/F/TAF) FDC tablets to BIC/LEN (75/50 mg) FDC tablets and placebo-to-match (PTM) B/F/TAF. Participants will receive a 2-day oral loading dose of LEN 600 mg on Day 1 and on Day 2, in addition to the daily doses of BIC/LEN FDC tablet starting on Day 1 up to end of blinded treatment (EBT) visit. Open-label (OL) Phase: Following treatment in the Blinded Phase, participants from Treatment Group 1 will receive BIC/LEN FDC tablets through Week 48 in the Open-label Phase. At the OL Week 48 visit, participants from Treatment Group 1 will be given the option to continue to receive BIC/LEN FDC tablets until the conclusion of the OL Phase.	Drug: Bictegravir; Tablets administered orally without regard to food; Other Names: GS-9883; Drug: Lenacapavir; Tablets administered orally without regard to food; Other Names: GS-6207; Drug: Placebo to match B/F/TAF; Tablets administered orally without regard to food
Experimental: Treatment Group 2: B/F/TAF (50/200/25 mg) + PTM BIC/LEN; Blinded Phase: Participants will continue with their B/F/TAF (50/200/25 mg) FDC tablets and start PTM BIC/LEN tablets on Day 1. Participants will receive PTM LEN tablets for 2 days (2 PTM LEN tablets on Day 1 and on Day 2. The blinded phase will continue until the EBT visit. Open Label Phase: Participants in Treatment Group 2 who complete the EBT visit will be given the option to enter the OL phase to receive BIC/LEN FDC tablets until the conclusion of the OL Phase.	Drug: Bictegravir; Tablets administered orally without regard to food; Other Names: GS-9883; Drug: Lenacapavir; Tablets administered orally without regard to food; Other Names: GS-6207; Drug: B/F/TAF; Tablets administered orally without regard to food; Other Names: Biktarvy ®; Drug: Placebo to match BIC/LEN; Tablets administered orally without regard to food

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of Participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm	Week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm	Week 48
Change From Baseline in Clusters of Differentiation 4 (CD4) Cell Count at Week 48	Baseline; Week 48
Treatment Group 1: Proportion of Participants with HIV-1 RNA ≥ 50 copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm	Week 96
Treatment Group 1: Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 96 as Determined by US FDA-defined Snapshot Algorithm	Week 96
Treatment Group 1: Change from Baseline in CD4 Cell Count at Week 96	Baseline; Week 96
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) through Week 48	From first dose date up to Week 48
Treatment Group 1: Percentage of Participants Experiencing Treatment-Emergent AEs through Week 96	From first dose date up to Week 96

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: March 20, 2024
• First Submitted That Met QC Criteria: March 20, 2024
• First Posted (Actual): March 27, 2024

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: GS-US-621-6290; 2023-510022-33 (Other Identifier: European Medicines Agency)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No