Pharmacodynamic Effects of Topical Omiganan in Patients With Mild to Moderate Atopic Dermatitis in a Randomized, Placebo-Controlled, Phase II Trial

Tessa Niemeyer-van der Kolk, Hein van der Wall, Geretta K Hogendoorn, Rianne Rijneveld, Sascha Luijten, Dirk C J G van Alewijk, Ellen H A van den Munckhof, Marieke L de Kam, Gary L Feiss, Errol P Prens, Jacobus Burggraaf, Robert Rissmann, Martijn B A van Doorn, Tessa Niemeyer-van der Kolk, Hein van der Wall, Geretta K Hogendoorn, Rianne Rijneveld, Sascha Luijten, Dirk C J G van Alewijk, Ellen H A van den Munckhof, Marieke L de Kam, Gary L Feiss, Errol P Prens, Jacobus Burggraaf, Robert Rissmann, Martijn B A van Doorn

Abstract

Omiganan is an indolicidin analog with antimicrobial properties that could be beneficial for patients with atopic dermatitis. In this randomized, double-blind, placebo-controlled, phase II trial we explored the efficacy, pharmacodynamics, and safety of topical omiganan once daily in 36 patients with mild to moderate atomic dermatitis. Patients were randomized to apply topical omiganan 1%, omiganan 2.5%, or vehicle gel to one target lesion once daily for 28 consecutive days. Small but significant improvements in local objective SCORing Atopic Dematitis index and morning itch were observed in the omiganan 2.5% group compared with the vehicle gel group (-18.5%; 95% confidence interval, -32.9 to -1.0; P = 0.04; and -8.2; 95% confidence interval, -16.3 to -0.2; P = 0.05, respectively). A shift from lesional to nonlesional skin microbiota was observed in both omiganan treatment groups, in contrast to the vehicle group. Thus, treatment with topical omiganan improved dysbiosis in patients with mild to moderate atopic dermatitis, and small but statistically significant improvements in clinical scores were detected. Our findings warrant further exploration in future clinical trials.

Trial registration: ClinicalTrials.gov NCT02456480.

Conflict of interest statement

G.L.F. was employed by Cutanea Life Sciences. The final draft was approved by G.L.F. on behalf of the sponsor, but no major comments were made. The authors declared no competing interests for this work.

© 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.

Figures

Figure 2
Figure 2
Change from baseline in body surface area, objective SCORing Atopic Dematitis (oSCORAD) index and morning and evening itch in the omiganan 1% and 2.5% treatment groups compared with the vehicle gel group. Change from baseline graphs: delta least‐squares mean (LSM) data over time of clinical assessments for (a) body surface area (BSA) and oSCORAD (b) of the target lesion. In the lower panels, patient‐reported outcomes are depicted, i.e., itch in the (c) morning and (d) evening.
Figure 3
Figure 3
Pharmacodynamic effects of topical omiganan in the omiganan 1%, omiganan 2.5%, and vehicle gel groups. (a) Transepidermal water loss (TEWL) over time is depicted, showing improvement in the treatment groups and the vehicle group. Relative mRNA expressions in skin punch biopsy of markers (b) interleukin‐31, (c) eotaxin, and (d) interferon‐γ in lesional vs. nonlesional skin in mild to moderate atopic dermatitis patients at baseline. Data presented as median with interquartile range. Statistical significance is as follows: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, based on a paired t‐test on log‐transformed data. (e) Relative mRNA expression of eotaxin per treatment group before treatment of lesional skin (day 0) and after end of treatment of lesional skin (day 28) and nonlesional (NL) skin. No treatment effect could be seen with this marker.
Figure 4
Figure 4
Course of cutaneous microbiome after omiganan treatment over time. Relative Staphylococcus abundance over time in the (a) omiganan 1%, (b) omiganan 2.5%, and (c) vehicle groups. A reduction is seen in both active treatment groups, but not in the vehicle group. Nonlesional boxes are presented as control on the right side. Median values are shown in blue above the boxplots.
Figure 5
Figure 5
Omiganan improves dysbiosis of the target lesion. (a) Staphylococcus abundance and (b) diversity index from baseline to day 28 (end of treatment) per treatment group, with P‐values of the differences calculated using a mixed model for data over time.
Figure 6
Figure 6
Correlation analysis of target lesion objective SCORing Atopic Dematitis (oSCORAD) index and Staphylococcus abundance. Correlations are shown between the (a) local target lesion oSCORAD index and Staphylococcus abundance in the microbiome and for the (b) target lesion oSCORAD and diversity index. (c,d) Delta correlations.
Figure 1
Figure 1
Flowchart of the study. QD = qualified dose (once daily).

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