Results of phase 2 trials exploring the safety and efficacy of omiganan in patients with human papillomavirus-induced genital lesions

Abstract

Aims: To assess safety and tolerability and explore pharmacodynamics and efficacy of omiganan in external anogenital warts (AGW) and vulvar high-grade squamous intraepithelial lesions (HSIL).

Methods: Two randomized controlled trials in patients with external AGW and vulvar HSIL were conducted. Patients received topical omiganan 2.5% or placebo gel once daily for 12 weeks with a follow-up of 12 weeks. Safety and tolerability were monitored and pharmacodynamics and clinical efficacy of omiganan were assessed by analysing lesion count, size and viral load. Self-reported pain, itch and quality of life were assessed by an electronic diary and questionnaire.

Results: Twenty-four AGW and 12 vulvar HSIL patients were enrolled. All patients had a high treatment adherence (99%). No serious adverse events occurred and all adverse events (n = 27) were mild, transient and self-limiting. The treatment groups were not different in terms of safety and tolerability, lesion count and size, and patient-reported outcomes pain, itch and quality of life. Human papillomavirus load significantly reduced after 12 weeks of treatment with omiganan compared to placebo (-96.6%; 95% confidence interval -99.9 to -7.4%; P = .045) in AGW patients only.

Conclusion: Topical omiganan appears to be safe in patients with AGW and vulvar HSIL and reduced human papillomavirus load after 12 weeks of treatment in AGW patients.

Trial registration: ClinicalTrials.gov NCT02849262 NCT02596074.

Keywords: dermatology; medication safety; pharmacodynamics; pharmacokinetics; virology.

Conflict of interest statement

G.F. was employee of the sponsor. All other authors have no competing interests to declare.

© 2019 The British Pharmacological Society.

Figures

Figure 1

Integrated flowchart of the anogenital warts (AGW) and vulvar high‐grade squamous intraepithelial lesions (HSIL) trial. In the AGW trials, 31 subjects were screened and 24 (77%) enrolled. Of the 24 remaining subjects, 16 were randomly assigned to treatment with omiganan and 8 to placebo. One subject in the omiganan group discontinued the intervention due to personal reasons, the end of study visit was performed prematurely. One subject in the placebo group was excluded from analysis in the follow‐up period because of use of concomitant medication for AGW. In the vulvar HSIL trials, 15 subjects were screened of whom 12 (80%) were enrolled. Of the 12 remaining subjects 8 were randomly assigned to treatment with omiganan and 4 to placebo. All subjects completed the study

Figure 2

Photography assessments of lesions over time. Photography of patients with anogenital warts and vulvar HSIL, both patients were treated with omiganan. Predose (day 0) the lesions are clearly visible. Upon treatment, the genital warts clearly resolve and the vulvar HSIL remained the same. The patient in the first picture had total clearance of the genital warts at EOS, but a postinflammatory hypopigmentation had occurred at the lesion site. Day 0 is before start of treatment, day 84 is at the end of treatment (EOT) and day 168 is at the end of study (EOS)

Figure 3

Viral load shown as change from baseline (CFB). From all swabs nucleic acid was isolated to determine the viral load of human papillomavirus (HPV) by use of quantitative polymerase chain reaction (qPCR) analysis of viral load in swabs was performed using a mixed model with treatment, time and treatment by time as fixed factors and subject as random factor. All statistical tests were 2‐tailed with an α‐level of 0.05. The viral load of anogenital warts patients decreases during the study period in the active treatment group, while the placebo group first shows an increase of viral load. A statistically significant difference was found when comparing the HPV load of anogenital warts patients treated with omiganan compared to placebo (–96.6%; 95% confidence interval –99.9 to – 7.4%; P = .045). The viral load of vulvar high‐grade squamous intraepithelial lesions (HSIL) patients remains stable during the study period and no statistical difference was found when comparing the HPV load of vulvar HSIL patients treated with omiganan compared to placebo. EOT, end of treatment