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The efficacy and safety of lenacapavir in heavily treated patients with multidrug-resistant HIV-1 infection are based on 52-week data from the CAPELLA trial, a randomized, placebo-controlled, double-blind, multicenter study.
The CAPELLA trial was conducted in 72 heavily treated patients with multidrug-resistant HIV-1 infection. Eligible participants were required to have a viral load of ≥400 copies/mL, documented resistance to at least two antiretroviral drugs in each of at least three drug classes (NRTI, NNRTI, PI, INSTI), and ≤2 fully active antiretroviral drugs remaining at baseline due to drug resistance, intolerance, limited drug access, contraindications, or other safety concerns.
The trial consisted of two cohorts. Participants were enrolled in the randomized cohort (Cohort 1, N=36) if they had an HIV-1 RNA reduction of <0.5 log10 from screening. Those with an HIV-1 RNA reduction of ≥0.5 log10 from screening, or who were enrolled after Cohort 1 reached its planned sample size, were assigned to the non-randomized cohort (Cohort 2, N=36).
During the 14-day functional monotherapy phase, participants in Cohort 1 were randomized in a 2:1 ratio to receive lenacapavir or placebo in a blinded manner while continuing their failing antiretroviral regimen. This phase was designed to establish the virological activity of lenacapavir. Following the functional monotherapy phase, participants who had received lenacapavir continued treatment with lenacapavir plus an optimized background regimen (OBR); those who had received placebo initiated lenacapavir plus OBR.
The mean age of participants in Cohort 1 was 52 years (range: 24 to 71), 72% were male, 46% were White, 46% were Black, and 9% were Asian. Twenty-nine percent of participants self-identified as Hispanic/Latino. The mean baseline plasma HIV-1 RNA was 4.3 log10 copies/mL (range: 2.3 to 5.4), with 19% of participants having a baseline viral load >100,000 copies/mL. The mean baseline CD4+ cell count was 161 cells/mm³ (range: 6 to 827), and 75% of participants had a CD4+ cell count <200 cells/mm³. The mean duration since participants first initiated HIV treatment was 24 years (range: 7 to 33); the mean number of antiretroviral drugs in their failing baseline regimen was 4 (range: 1 to 7). In the randomized cohort, the percentages of participants with known resistance to at least two drugs in the NRTI, NNRTI, PI, and INSTI classes were 97%, 94%, 78%, and 75%, respectively. In Cohort 1, 53% of participants had no fully active drugs in their initial failing regimen, 31% had 1 fully active drug, and 17% had ≥2 fully active drugs (including 6% of participants who were receiving fostemsavir, an investigational agent at the start of the CAPELLA trial).
FDA，2024.11
