A Phase 3, Randomized, Double-blind, Active-controlled Study to Evaluate a Switch to an Oral Weekly Islatravir/Lenacapavir Regimen in People With HIV-1 Who Are Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir (B/F/TAF)
Samir Gupta, MD
Primary Investigator
Brief description of study
The goal of this clinical study is to learn about the safety and efficacy of switching to once weekly tablet of islatravir/lenacapavir (ISL/LEN) regimen versus continuing standard treatment of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with human immunodeficiency virus (PWH) who are virologically suppressed (HIV-1 RNA levels < 50 copies/mL) on B/F/TAF for ≥ 6 months prior to screening.
The primary objective is to evaluate the efficacy of switching to oral weekly ISL/LEN tablet regimen versus continuing B/F/TAF in virologically suppressed PWH at Week 48.
Detailed description of study
Participants who provide written consent and meet all eligibility criteria will be randomized in a
1:1 ratio to 1 of the following 2 treatment groups:
• Treatment Group 1:
Loading dose of FDC ISL/LEN 0.5/300 mg 2 tablets administered orally on Day 1 and
Day 2 (total 4 tablets), without regard to food
FDC ISL/LEN 2/300 mg tablet administered orally, once weekly, without regard to food,
from Day 8 onwards
Placebo-to-match (PTM) B/F/TAF (50/200/25 mg) tablet administered orally, once daily,
without regard to food, from Day 1 onwards
• Treatment Group 2:
PTM FDC ISL/LEN 0.5/300 mg 2 tablets administered orally on Day 1 and Day 2<br>(total 4 tablets), without regard to food
PTM FDC ISL/LEN 2/300 mg tablet administered orally, once weekly, without regard to
food, from Day 8 onwards
B/F/TAF 50/200/25 mg tablet administered orally, once daily, without regard to food,
from Day 1 onwards
Open-label Extension (OLE) Phase:
After Week 96, all participants will continue to take their blinded study drug and attend visits
every 12 weeks until the end of blinded treatment visit. Once the last participant completes the
Week 96 visit and the sponsor completes the Week 96 analysis, all participants will return to the
clinic (preferable within 30 days) for an end of blinded treatment visit. At the end of blinded
treatment visit, if safety and efficacy of ISL/LEN are demonstrated following review of
unblinded data, participants will be given the option to receive ISL/LEN FDC in an OLE phase
until ISL/LEN FDC becomes available, or until the sponsor elects to discontinue the study,
whichever occurs first. Participants who opt out of receiving ISL/LEN FDC in the OLE phase
will discontinue from the study.
Participants receiving B/F/TAF during the blinded phase who enter the OLE phase will attend a
Week 4 visit during the OLE phase.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: HIV-1
-
Age: 18 years - 100 years
-
Gender: All
Key Inclusion Criteria:
- HIV-1 RNA < 50 copies/mL for ≥ 6 months before screening, as documented by:
- One HIV-1 RNA < 50 copies/mL immediately preceding the 24 week period prior to screening.
- Within 24 weeks prior to screening, if HIV-1 RNA results are available, all levels must be < 50 copies/mL.
- 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.
- Individuals are receiving B/F/TAF for ≥ 6 months prior to screening and willing to continue until Day 1.
- 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:
- Positive HBV surface antigen OR
- 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:
- Creatinine clearance (CLcr) ≤ 30 mL/min according to the Cockcroft-Gault formula
- Alanine aminotransferase > 5 x upper limit of normal (ULN)
- Direct bilirubin > 1.5 x ULN
- Platelets < 50,000/μL
- Hemoglobin < 8.0 g/dL
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
