Open‐Label, Randomized Pilot Study to Evaluate Safety and Tolerability of a Novel Dermal Nanoparticulate Imiquimod Formulation in the Treatment of Actinic Keratosis

Objective Actinic keratoses (AKs) are among the most common precancerous lesions in fair‐skinned populations and are of considerable clinical relevance. Topical imiquimod has been established as an effective treatment option, although it is associated with local adverse events. Aim To assess the tolerability and safety of a novel nanoparticle‐based imiquimod formulation (IMI.Gel) for the treatment of AK in comparison to the reference product Aldara. Secondary endpoints included efficacy, cosmetic outcomes, and patient‐reported quality of life. Methods In an open‐label, 1:1 randomized monocentric Phase I/II study patients with clinically diagnosed AK lesions were enrolled. Both groups received topical therapy three times per week over a 4‐week period. Efficacy was evaluated at Week 8. In cases of persistent lesions, a second treatment cycle was administered. Follow‐up was conducted over a 12‐month period with three predefined study visits. Results A total of 81 patients were randomized (IMI.Gel n = 41; Aldara n = 40). The mean age was 72 years (range 44–89), and 78% of participants were male. No statistically significant differences were observed between the two treatment groups regarding tolerability (local skin reactions), safety (adverse events), or efficacy (lesion reduction). A second treatment cycle was performed in 73.0% of patients in the IMI.Gel group and 52.9% in the Aldara group. Complete response rates at 12 months were 48.4% for IMI.Gel and 48.5% for Aldara. Both groups showed a significant improvement in quality of life, as measured by a reduction in the Dermatology Life Quality Index of 1.12 points (IMI.Gel) and 1.02 points (Aldara) after 12 months. Conclusion The nanoparticle‐based IMI.Gel proved to be a safe and tolerable alternative to the standard therapy with Aldara. Trial Registration: EudraCT number: 2015‐002203‐28