Three Phase III Randomized Controlled Trials of Topical Resiquimod 0.01% Gel to Reduce Anogenital Herpes Recurrences.

Publication Type:

Journal Article


Antimicrobial agents and chemotherapy (2014)


2014, April 2014, Vaccine and Infectious Disease Division


Resiquimod, a toll-like receptor 7 and 8 agonist, stimulates production of cytokines that promote an antigen-specific T helper type 1 acquired immune response. Animal and phase II human trials showed post-treatment efficacy in reducing recurrent herpes lesion days and/or time to first recurrence. Three phase III randomized, double-blind, vehicle-controlled trials of topical resiquimod to reduce anogenital herpes recurrences were conducted in healthy adults with ≥4 recurrences within the prior year. Participants applied resiquimod 0.01% or vehicle gel 2 times per week for 3 weeks to each recurrence for 12 months. Trials 1 and 2 had 2:1 resiquimod:vehicle randomization. Trial 3 had 1:1:1 randomization for resiquimod plus valacyclovir 500 mg orally twice daily for 5 days (RESI/VAL), resiquimod plus oral placebo (RESI/PLA), and vehicle plus oral placebo (VEH/PLA). Median time to first recurrence was similar for resiquimod and vehicle [Trial 1: 60 and 56 days, p=0.7; Trial 2: 54 and 48 days, p=0.47; Trial 3: 51 (RESI/VAL), 55 (RESI/PLA), and 44 (VEH/PLA) days, p=NS]. Median time to healing of initial treated recurrence was longer for resiquimod [Trial 1: 18 versus 10 days, p<0.001; Trial 2: 19 versus 13 days, p=0.16; Trial 3: 14 (RESI/VAL), 16 (RESI/PLA), and 8 (VEH/PLA) days, p<0.001]. In Trials 1 and 2, moderate to severe erythema and erosion/ulceration at the application site were more common in resiquimod recipients. In conclusion, no post-treatment efficacy of resiquimod 0.01% gel was observed. Increased application site reactions and initial recurrence healing time are consistent with resiquimod-induced cytokine effects.