A Phase I, Randomized, Controlled Clinical Study of CC-11050 in People Living With HIV With Suppressed Plasma Viremia on Antiretroviral Therapy (APHRODITE).

ABSTRACT

OBJECTIVE: Phosphodiesterase 4 inhibitors (PDE4i) are novel anti-inflammatory medications that have been approved for rheumatologic diseases and have been tested as host-directed therapy in tuberculosis. We examined the safety of CC-11050, a potent PDE4i in people living with HIV (PLWH) with suppressed HIV plasma viremia. We hypothesized that CC-11050 could be used to modulate HIV-related inflammation. METHOD: Thirty PLWH on antiretroviral therapy (ART) ≥ 1 year with suppressed HIV viremia were enrolled and randomized 21 to 12 weeks of CC-11050 200mg twice daily or placebo with follow-up at weeks 2, 4, 8, 12, and 16. Primary endpoint was safety. Secondary endpoints were the effect of CC-11050 on cytokines, monocyte, and T-cell activation and potential pharmacokinetic interaction between CC-11050 and Efavirenz (EFV). RESULTS: At baseline, median age was 49.5 years and CD4 count 459 cells/µL. Most frequent adverse events (grade 1 and 2 only) in CC-11050 group were headache, diarrhea, nausea, cough, nasal congestion, and restlessness. Over a 12-week period, the CC-11050 group had lower level of IL-8, adjusted for baseline level, group, and week (0.72-fold, P = .02), lower percentage of NK cells (0.87-fold, P = .02) and higher IL-6 level (1.48-fold, P = .03) compared to placebo (0.87-fold, P = .02). CC-11050 and EFV co-administration did not reveal any pharmacokinetic interaction. CONCLUSIONS: CC-11050 was well tolerated in PLWH, without affecting CD4 counts or plasma viremia, and led to a decrease in NK cells and plasma IL-8 level after 12-weeks of administration. Further study will be needed to elucidate the efficacy of CC-11050 as potential anti-inflammatory adjuvant strategy in HIV.