Study to Compare an Oral Weekly Islatravir/Lenacapavir Regimen With Standard of Care in Virologically Suppressed People With HIV-1 (ISLEND-2)

Gilead Sciences

Status and phase: Enrolling; Phase 3

Conditions: HIV-1-Infection

Treatments: Drug: Antiretroviral Combinations; Drug: ISL/LEN

Study type: Interventional

Funder types: Industry

Identifiers

NCT06630299

2024-514047-28 (Other Identifier)

GS-US-563-5926

Details and patient eligibility

About

The goal of this clinical study is to learn more about the safety and efficacy of switching to a once weekly tablet of islatravir/lenacapavir (ISL/LEN) regimen versus continuing standard of care treatment in people with human immunodeficiency virus (PWH) who are virologically suppressed (HIV-1 RNA levels < 50 copies/mL) on a stable standard of care regimen for ≥ 6 months prior to screening. The standard of care includes 2 or 3 medicines, antiretroviral agents (ARVs).

The primary objective of the study is to evaluate the efficacy of switching to oral weekly ISL/LEN tablet regimen versus continuing standard of care in virologically suppressed PWH at Week 48.

Enrollment: 600 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• HIV-1 RNA < 50 copies/mL for ≥ 6 months before screening, as documented by:

  1. One HIV-1 RNA < 50 copies/mL immediately preceding the 24 weeks period prior to screening.
  2. Within 24 weeks prior to screening, if HIV-1 RNA results are available, all levels must be < 50 copies/mL.
  3. During the 6 to 12 months period prior to screening, transient detectable viremia ≥ 50 copies/mL is acceptable ("blip") as long as it is not confirmed on 2 consecutive visits.

• Plasma HIV-1 RNA levels < 50 copies/mL at screening.

• Are receiving guideline-recommended standard of care treatment such as International Antiviral Society (IAS), Department of Health and Human Services (DHHS), European AIDS Clinical Society (EACS) consisting of 2 or 3 ARVs for ≥ 6 months prior to screening and willing to continue until Day 1. Individuals in Treatment Group 2 must also be willing to continue their standard of care through at least Week 96.

• Individuals assigned female at birth and of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified methods of contraception.

Key Exclusion Criteria:

• Prior virologic failure.

• Prior use of, or exposure to, ISL or LEN.

• Active, serious infections requiring parenteral therapy within 30 days before randomization.

• Active tuberculosis infection.

• Acute hepatitis within 30 days before randomization.

• Hepatitis B virus (HBV) infection, as determined below at the screening visit:

  1. positive HBV surface antigen OR
  2. positive HBV core antibody and negative HBV surface antibody. Note: individuals found to be susceptible to HBV infection (eg negative hepatitis B surface antibody at the screening visit, regardless of prior HBV vaccination history) should be recommended to receive HBV vaccination.

• Active hepatitis C virus (HCV) coinfection, defined as detectable HCV RNA. Note: individuals with prior/inactive HCV infection (defined as undetectable HCV RNA) may be enrolled.

• Any of the following laboratory values at screening:

  1. Creatinine clearance (CLcr) ≤ 30 mL/min according to the Cockcroft-Gault formula
  2. Alanine aminotransferase (ALT) > 5 x upper limit of normal (ULN)
  3. Direct bilirubin > 1.5 x ULN
  4. Platelets < 50,000/μL
  5. Hemoglobin < 8.0 g/dL

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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600 participants in 3 patient groups

ISL/LEN

Experimental group

Description:

Participants will receive an initial dose of ISL/LEN (Dose A), followed by once weekly ISL/LEN (Dose B) from Day 8 onwards up to Week 96.

Treatment:

Drug: ISL/LEN

Standard of Care Treatment

Active Comparator group

Description:

Participants will continue standard of care treatment with 2-3 ARVs up to Week 96: * Integrase Strand Transfer Inhibitor (INSTI) class: INSTI combined with 1 or 2 nucleoside reverse transcriptase inhibitors (NRTIs; bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF; coformulated; Biktarvy®), dolutegravir (DTG)/abacavir (ABC)/lamivudine (3TC), DTG+ TAF or TDF (TXF)/emtricitabine (FTC; Emtriva®), DTG/tenofovir disoproxil fumarate (TDF; Viread®)/3TC, DTG/3TC, raltegravir (RAL) + TXF/FTC, RAL+TDF/3TC, elvitegravir (EVG; Vitekta®)/cobicistat (c; Tybost®)/TXF/FTC), or * PI class: Boosted protease inhibitor (PI) combined with 2 NRTIs (darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF; coformulated), boosted darunavir (DRV)+TXF/FTC, boosted DRV+TDF/3TC), or * NNRTI class: Nonnucleoside reverse transcriptase inhibitor (NNRTI) combined with 2 NRTIs (doravirine (DOR)/TDF/3TC, DOR+TXF/FTC, DOR+TDF/3TC, rilpivirine (RPV)/TXF/FTC, RPV+TXF/FTC, RPV+TDF/3TC)

Treatment:

Drug: ISL/LEN

Drug: Antiretroviral Combinations

Extension Phase

Experimental group

Description:

At the end of randomized treatment visit, if safety and efficacy of ISL/LEN are demonstrated following review of randomized data, participants will be given the option to receive ISL/LEN tablets in an extension phase until ISL/LEN becomes available or until the sponsor elects to discontinue the study, whichever occurs first. Participants receiving ISL/LEN during the randomized phase will continue to take ISL/LEN weekly. Participants receiving standard of care during the randomized phase will take an initial dose of ISL/LEN (Dose A), followed by once weekly ISL/LEN (Dose B) from Day 8 onwards.

Treatment:

Drug: ISL/LEN