Phase 1 studies to assess the safety, tolerability and pharmacokinetics of JTE-052 (a novel Janus kinase inhibitor) ointment in Japanese healthy volunteers and patients with atopic dermatitis

Abstract

The purpose of the present two phase 1 studies was to assess the safety, tolerability and pharmacokinetics for topical application of a novel Janus kinase (JAK) inhibitor, JTE-052, in Japanese healthy adult male volunteers and Japanese adult patients with atopic dermatitis (AD). Additionally, exploratory investigation was performed on the efficacy for disease severity and pruritus score in AD patients. In the QBX1-1 study, the cutaneous safety of JTE-052 ointment by a patch test and a photo patch test was assessed in an intra-individual comparative study using placebo ointment, white petrolatum and non-application as comparators. The study demonstrated that JTE-052 ointment would be associated with a low potential for phototoxicity but had no potential for skin irritation or photoallergy. In the QBX1-2 study, it was revealed that the systemic exposure to JTE-052 in both healthy volunteers with normal skin and AD patients with inflamed skin was low in application of not only 1% but also 3% JTE-052 ointment. JTE-052 ointments of 1% and 3% were generally safe and well tolerated in both populations. In a repeated twice-daily application for 7 days, the efficacy of JTE-052 ointment to AD patients was observed with both 1% and 3% ointments in the exploratory investigations evaluated by Eczema Area and Severity Index, Investigator's Global Assessment and Numeric Rating Scale assessments. The mean scores for each assessment declined from the baseline throughout the study. These results suggest that the treatment of JTE-052 ointment is generally safe and effective in AD patients, although further large confirmatory studies are needed.

Keywords: JTE-052; atopic dermatitis; patch test; pharmacokinetics; topical.

Figure 1

Subject disposition. Study design and subject allocation schema for QBX1‐1 study and QBX1‐2 study.

Figure 2

Application sites: 0.03%, 0.1%, 0.3%, 1%, 3% JTE‐052, placebo, white petrolatum and the negative control (non‐application) were applied using a Finn Chamber^® for the patch test on the left paravertebral side and for the photo patch test on the right paravertebral side of the upper back. Individual investigational products (including the negative control) were randomly assigned to the application sites of each subject using the circuit method.

Figure 3

Mean (+ standard deviation) plasma concentration‐time profiles of JTE‐052 in atopic dermatitis (AD) patients on (a) day 1 and (b) day 7 after the application of 1% or 3% JTE‐052 ointment. Subjects were treated with 1% or 3% JTE‐052 ointment twice daily for 7 days in the morning and the evening with a 12‐h interval. Concentration values below the lower limits of quantification were dealt with zero (0) in the calculation of descriptive statistics for each time point.

Figure 4

(a) Mean (± standard deviation) absolute changes in Eczema Area and Severity Index (EASI) score or (b) percentage changes in EASI score. Subjects were treated with placebo, 1% or 3% JTE‐052 ointment twice daily for 7 days in the morning and the evening with a 12‐h interval.

Figure 5

Patient distribution of absolute changes in the Investigator's Global Assessment (IGA) score on day 8. Subjects were treated with placebo, 1% or 3% JTE‐052 ointment twice daily for 7 days in the morning and the evening with a 12‐h interval.

Figure 6

Mean (± standard deviation) absolute changes in Numeric Rating Scale (NRS). Subjects were treated with placebo, 1% or 3% JTE‐052 ointment twice daily for 7 days in the morning and the evening with a 12‐h interval. The assessment of NRS was performed twice daily from day −1 (hospitalization) to day 9 (1 day after the end of application); (a) the period “from bedtime to morning awakening” was assessed at morning awakening and (b) the period “from morning awakening to bedtime” was assessed at bedtime.