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

JRCT ID: jRCT2051240218

Registered date:19/12/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: HIV-1-Infection
• Date of first enrollment: 18/12/2024
• Target sample size: 600
• Countries of recruitment: US,Japan
• Study type: Interventional

Intervention(s)

Experimental: ISL/LEN
- 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.
Interventions:
- Drug: ISL/LEN (Tablet administered orally)

Active Comparator: Standard of Care Treatment
- 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)
Interventions:
- Drug: ISL/LEN (Tablet administered orally)
- Drug: Antiretroviral Combinations(2 or 3 antiretrovirals (ARVs) administered as defined by the investigator, according to the prescribing information.)

Experimental: Extension Phase
- 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.
Interventions:
- Drug: ISL/LEN (Tablet administered orally)

Outcome(s)

• Primary Outcome: Proportion of participants with HIV-1 RNA >= 50 copies/mL at Week 48 as Determined by the United States (US) Food and Drug Administration (FDA)-defined Snapshot Algorithm [Time Frame: Week 48]

Secondary Outcome

Proportion of Participants with HIV-1 RNA >= 50 copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm [Time Frame: Week 96]

Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 48 and Week96 as Determined by the US FDA-defined Snapshot Algorithm [Time Frame: Week 48, Week96]

Change from Baseline in clusters of differentiation 4 (CD4) T-Cell Count at Week 48 and Week96 [Time Frame: Baseline, Week 48, Week96]

Proportion of Participants Discontinuing ISL/LEN due to Treatment-Emergent Adverse Events (TEAEs) [Time Frame: First dose date up to Week 96]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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.

Exclude 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/uL
5. Hemoglobin < 8.0 g/dL

Related Information

• Primary Sponsor: Watanabe Takanobu
• Secondary ID(s): NCT06630299,2024-514047-28