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

• ClinicalTrials.gov Identifier: NCT05502341
• Recruitment Status: Recruiting
• First Posted: August 16, 2022
• Last Update Posted: May 3, 2024
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: August 5, 2022
• First Posted Date: August 16, 2022
• Last Update Posted Date: May 3, 2024
• Actual Study Start Date: August 16, 2022
• Estimated Primary Completion Date: January 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 12, 2022)

• Phase 2: Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm [ Time Frame: Week 24 ]
• Phase 3: Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm [ Time Frame: Week 48 ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 12, 2024)

• Phase 2: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm [ Time Frame: Week 24 ]
• Phase 2: Change From Baseline in CD4 Cell Count at Week 24 [ Time Frame: Baseline, Week 24 ]
• Phase 2: Percentage of Participants Experiencing Treatment-emergent Adverse Events (AEs) Through Week 24 [ Time Frame: First dose date up to Week 24 ]
• Phase 2: Pharmacokinetic (PK) Parameter: Cmax of Bictegravir (BIC) and Lenacapavir (LEN) at Steady State [ Time Frame: Day 1 up to Week 24 ]
  Cmax is defined as the maximum observed concentration of drug.
• Phase 2: PK Parameter: AUCtau of BIC and LEN at Steady State [ Time Frame: Day 1 up to Week 24 ]
  AUCtau is defined as the area under the concentration versus time curve over the dosing interval.
• Phase 2: PK Parameter: Ctau of BIC and LEN at Steady State [ Time Frame: Day 1 up to Week 24 ]
  Ctau is defined as the observed drug concentration at the end of the dosing interval.
• Phase 3: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm [ Time Frame: Week 48 ]
• Phase 3: Change From Baseline in CD4 Cell Count at Week 48 [ Time Frame: Baseline, Week 48 ]
• Phase 3 (BIC/LEN 75 mg/50 mg FDC): Proportion of Participants from With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm [ Time Frame: Week 96 ]
• Phase 3 (BIC/LEN 75 mg/50 mg FDC): Change From Baseline in CD4 Cell Count at Week 96 [ Time Frame: Baseline, Week 96 ]
• Phase 3: Percentage of Participants Experiencing Treatment-emergent AEs Through Week 48 [ Time Frame: First dose date up to Week 48 ]
• Phase 3 (BIC/LEN 75 mg/50 mg FDC): Proportion of Participants from Experiencing Treatment-emergent AEs Through Week 96 [ Time Frame: Week 96 ]

Original Secondary Outcome Measures (submitted: August 12, 2022)

• Phase 2: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm [ Time Frame: Week 24 ]
• Phase 2: Change From Baseline in CD4 Cell Count at Week 24 [ Time Frame: Baseline, Week 24 ]
• Phase 2: Percentage of Participants Experiencing Treatment-emergent Adverse Events (AEs) Through Week 24 [ Time Frame: First dose date up to Week 24 ]
• Phase 2: Pharmacokinetic (PK) Parameter: Cmax of Bictegravir (BIC) and Lenacapavir (LEN) at Steady State [ Time Frame: Day 1 up to Week 24 ]
  Cmax is defined as the maximum observed concentration of drug.
• Phase 2: PK Parameter: AUCtau of BIC and LEN at Steady State [ Time Frame: Day 1 up to Week 24 ]
  AUCtau is defined as the area under the concentration versus time curve over the dosing interval.
• Phase 2: PK Parameter: Ctau of BIC and LEN at Steady State [ Time Frame: Day 1 up to Week 24 ]
  Ctau is defined as the observed drug concentration at the end of the dosing interval.
• Phase 3: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm [ Time Frame: Week 48 ]
• Phase 3: Change From Baseline in CD4 Cell Count at Week 48 [ Time Frame: Baseline, Week 48 ]
• Phase 3: Percentage of Participants Experiencing Treatment-emergent AEs Through Week 48 [ Time Frame: First dose date up to Week 48 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Compare Bictegravir/Lenacapavir Versus Current Therapy in People With HIV-1 Who Are Successfully Treated With a Complicated Regimen
• Official Title: An Operationally Seamless Phase 2/3 Randomized, Open-label, Multicenter, Active-Controlled Study to Evaluate the Safety and Efficacy of Bictegravir/Lenacapavir Versus Stable Baseline Regimen in Virologically Suppressed People With HIV-1 on Stable Complex Treatment Regimens
• Brief Summary: The goal of this clinical study is to learn more about the effects of switching to the study drugs, bictegravir (BIC) plus lenacapavir (LEN), versus current therapy (Phase 2) and BIC/LEN fixed-dose combination (FDC) versus current therapy (Phase 3) in people living with HIV (PWH).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV-1-infection

Intervention

• Drug: Bictegravir
  Tablets administered orally without regard to food
  Other Name: GS-9883
• Drug: Lenacapavir
  Tablets administered orally without regard to food
  Other Name: GS-6207
• Drug: BIC/LEN FDC
  Tablets administered orally without regard to food
• Drug: Stable Baseline Regimen

  SBR will include a combination of antiretroviral (ARV) regimen. ARV regimen may include the following, except for participants taking a single tablet regimen or taking a complete parenteral regimen (Cabenuva).

  • Nucleos(t)ide Reverse Transcriptase Inhibitors:

    • Abacavir
    • Emtricitabine
    • Lamivudine
    • Tenofovir alafenamide
    • Tenofovir disoproxil fumarate
    • Zidovudine

  • Non-Nucleosite Reverse Transcriptase Inhibitors:

    • Delavirdine
    • Efavirenz
    • Nevirapine
    • Rilpivirine
    • Doravirine

  • Integrase Inhibitors:

    • Bictegravir
    • Cabotegravir
    • Dolutegravir
    • Elvitegravir
    • Raltegravir

  • Protease Inhibitors:

    • Atazanavir
    • Darunavir
    • Fosamprenavir
    • Indinavir
    • Lopinavir
    • Nelfinavir
    • Saquinavir
    • Tipranavir

  • Chemokine Co-receptor 5 (CCR5) Antagonist:

    • Maraviroc

  • Fusion Inhibitors:

    • Enfuvirtide

  • gp120 Attachment Inhibitor:

    • Fostemsavir

  • Anti-CD4 Monoclonal Antibodies:

    • Ibalizumab-uiyk

Study Arms

• Experimental: Phase 2: Bictegravir (BIC) 75 mg + Lenacapavir (LEN) 25 mg

  Participants will switch from their stable baseline regimen (SBR) to a regimen of BIC 75 mg + LEN 25 mg. Participants will receive a 2-day loading dose regimen of LEN 600 mg, in addition to the daily doses of BIC 75 mg + LEN 25 mg starting on Day 1 up to the end of randomized treatment (ERT) visit, participants will be treated for at least 24 weeks during the Randomized Period.

  Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN 75 mg/50 mg fixed dose combination (FDC).

  Interventions:

  • Drug: Bictegravir
  • Drug: Lenacapavir
• Experimental: Phase 2: BIC 75 mg + LEN 50 mg

  Participants will switch from their SBR to a regimen of BIC 75 mg + LEN 50 mg. Participants will receive a 2-day loading dose regimen of LEN 600 mg, in addition to the daily doses of BIC 75 mg + LEN 50 mg starting on Day 1 up to the ERT visit, participants will be treated for at least 24 weeks during the Randomized Period.

  Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN 75 mg/50 mg FDC.

  Interventions:

  • Drug: Bictegravir
  • Drug: Lenacapavir
• Active Comparator: Phase 2: Stable Baseline Regimen (SBR)

  Participants will continue with their SBR per prescription for up to the ERT visit, participants will be treated for at least 24 weeks during the Randomized Period.

  Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN 75 mg/50 mg FDC.

  Intervention: Drug: Stable Baseline Regimen
• Experimental: Phase 3: BIC/LEN 75 mg/50 mg Fixed-dose Combination (FDC)

  Participants will switch from their SBR to a regimen of BIC/LEN 75 mg/50 mg FDC. Participants will receive a 2-day loading dose regimen of LEN 600 mg, in addition to the daily doses of BIC/LEN 75 mg/50 mg FDC starting on Day 1 up to the ERT visit, participants will be treated for at least 48 weeks during the Randomized Period.

  Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN 75 mg/50 mg FDC.

  Intervention: Drug: BIC/LEN FDC
• Active Comparator: Phase 3: Stable Baseline Regimen

  Participants will continue with their SBR per prescription for up to the ERT visit, participants will be treated for at least 48 weeks during the Randomized Period.

  Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN 75 mg/50 mg FDC.

  Intervention: Drug: Stable Baseline Regimen

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 12, 2022): 671
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 2028
• Estimated Primary Completion Date: January 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• If plasma HIV-1 RNA measurements in the 6 months prior to screening are available, all levels must be < 50 copies/mL.
• At least one documented plasma 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.

• Currently receiving a complex antiretroviral (ARV) regimen due to previous viral resistance, or intolerance, or contraindication to existing single-tablet regimens (STR), and on this regimen for at least 6 months prior to the screening visit. The criteria to define a complex regimen in this study are as follows:

  • A regimen containing a boosted protease inhibitor or a nonnucleos(t)ide reverse transcriptase inhibitor (NRTI) plus at least 1 other third agent (ie, an agent from a class other than NRTIs) (eg, bictegravir/emtricitabine/tenofovir alafenamide (coformulated; Biktarvy®)(BVY) + darunavir/cobicistat, BVY + etravirine), or
  • A regimen of ≥ 2 pills/day, or a regimen requiring dosing more than once daily, or
  • A regimen containing parenteral agent(s) (excluding a complete long-acting injectable regimen, such as intramuscular cabotegravir plus rilpivirine) as well as oral agents.
• No documented or suspected resistance to bictegravir (BIC).
• Estimated glomerular filtration rate ≥ 15 mL/min according to the Cockcroft-Gault formula for creatinine clearance (CLcr) who are not on renal replacement therapy.

Key Exclusion Criteria:

• Prior use of, or exposure to, lenacapavir (LEN)
• Active tuberculosis infection
• Chronic hepatitis B virus (HBV) infection

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Argentina, Australia, Canada, Dominican Republic, France, Germany, Italy, Japan, Korea, Republic of, Puerto Rico, South Africa, Spain, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT05502341
• Other Study ID Numbers: GS-US-621-6289; 2022-500929-33 ( Other Identifier: European Medicines Agency ); DOH-27-052023-8574 ( Other Identifier: South African Clinical Trial Registry )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Gilead Sciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Gilead Sciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: May 2024