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A Phase II/III, Multicenter, Randomized, Double-Blind, Vehicle-Controlled, Parallel-Group Study of M610101 in Patients with Atopic Dermatitis

A phase II/III Study of M610101 in Patients with Atopic Dermatitis

298

The demographic and other baseline characteristics in the full analysis set (FAS) were generally similar across the treatment groups, except for the proportion of participants with an Eczema Area and Severity Index (EASI) score over 7. In total, there were 173 male (58.1%) and 125 female participants (41.9%). The mean values (SD) for age, weight, and duration of atopic dermatitis were 32.6 (13.2) years, 61.29 (12.77) kg, and 22.10 (13.59) years, respectively. The number of participants with an Investigator's Global Assessment (IGA) score of 2 and 3 were 101 (33.9%) and 197 (66.1%), respectively. The mean value (SD) for EASI was 8.811 (4.382), and it was generally similar across the treatment groups, however, the proportion of participants with an EASI score over 7 was higher in the 0.75% M610101 group, with 70 participants (69.3%), compared to the 1.5% M610101 group (57 participants [58.8%]) and the vehicle group (56 participants [56.0%]). The mean value (SD) for percentage of Body Surface Area (%BSA) was 13.39% (4.85%), and the number of participants with %BSA less than 10 and 10 or more were 72 (24.2%) and 226 (75.8%), respectively.

Out of the 406 registered participants, 298 (0.75% M610101 group: 101 participants, 1.5% M610101 group: 97 participants, and vehicle group: 100 participants [in the same order]) were randomized and all received the study drug. The number of participants not randomized was 108, and the most common reasons for not being randomized were "failure to meet eligibility criteria" and "protocol violation/safety issue," each accounting for 42 participants. A total of 251 participants (92, 93, and 66 participants, respectively) completed the trial. There were 47 participants (9, 4, and 34 participants, respectively) who discontinued the study, and the number of discontinuations in the vehicle group was higher compared to the M610101 groups. The primary reasons for discontinuation were "withdrawal by participant" (2, 0, and 15 participants, respectively), "%BSA excluding scalp exceeding 20%" (3, 2, and 11 participants, respectively). There were 271 participants (91, 87, and 93 participants, respectively) who transitioned to the follow-up visit. The only participant who did not transition to the follow-up visit was from the vehicle group, and the reason was "withdrawal by participant".

- The safety analysis set included 298 participants (0.75% M610101 group: 100 participants, 1.5% M610101 group: 98 participants, vehicle group: 100 participants) (in the same order). - The incidence of adverse events (AEs) was 48.0% (48 of 100), 46.9% (46 of 98), and 47.0% (47 of 100), respectively, showing a similar rate across all groups. Of these, the incidence of AEs related to the study drug was 6.0% (6 of 100), 10.2% (10 of 98), and 17.0% (17 of 100), with the vehicle group having the highest incidence. - No AEs leading to death occurred. Other serious AE occurred in 1 participant each in the 0.75% M610101 group (foot fracture) and the 1.5% M610101 group (epilepsy). They were of Grade 3 in severity and not related to the study drug. - Among the relatively common AEs, the AEs that were related to the study drug and occurred with a numerically higher incidence in the 0.75% or 1.5% M610101 group compared to the vehicle group were acne (2.0%, 2.0%, 0%), herpes simplex (1.0%, 1.0%, 0%), application site acne (0%, 2.0%, 1.0%), and application site folliculitis (0%, 2.0%, 1.0%). - The incidence of AEs requiring withdrawal, dose reduction, or interruption of the study drug was 4.0% (4 of 100), 4.1% (4 of 98), and 12.0% (12 of 100), respectively. Of these, the incidence of AEs related to the study drug was 2.0% (2 of 100), 3.1% (3 of 98), and 8.0% (8 of 100), respectively. The incidence of AEs requiring withdrawal, dose reduction, or interruption of the study drug, regardless of their relationship to the study drug, was higher in the vehicle group compared to the M610101 groups. - Among AEs of special interest, the incidence of infections was 23.0% (23 of 100), 22.4% (22 of 98), and 14.0% (14 of 100), respectively, which was higher in the M610101 groups compared to the vehicle group. The incidence of AEs of special interest other than infections (cytopenias, thromboembolic and thrombocytosis events, increased lipids, and liver function test elevations) was low in all groups. No AEs corresponding to malignant tumors were observed. The severity of infections observed in this study was all Grade 1 or Grade 2, which was consistent with the expected known safety profile of M610101, and no new safety concerns were identified. - No clinically significant abnormalities were noted in any of clinical laboratory values, vital signs, or ECGs.

- All 298 participants who were randomized and received the study drug (0.75% M610101 group: 101 participants, 1.5% M610101 group: 97 participants, vehicle group: 100 participants) were included in the FAS. - The between-group differences (with a two-sided 95% confidence interval) in the proportion of participants achieving IGA-TS (IGA score of 0 or 1 with an IGA score improvement of 2 or more grades from baseline) at Week 8, the primary endpoint, were 31.7% (22.1% to 41.4%) for the 0.75% M610101 group compared to the vehicle group, and 37.0% (26.8% to 47.1%) for the 1.5% M610101 group compared to the vehicle group. The results of between-group comparison showed the superiority of both the 0.75% M610101 group and the 1.5% M610101 group to the vehicle group with a P < 0.0001. Additionally, the 1.5% M610101 group had a higher proportion of participants achieving IGA-TS on every assessment day compared to the 0.75% M610101 group. - For the secondary endpoints, the proportion of participants who achieved an improvement of 75% or more in the EASI, the percent change in the EASI, mean weekly changes in the Peak Pruritus Numerical Rating Scale (PP-NRS) and in the Sleep Disturbance-Numerical Rating Scale (SD-NRS), and the change in the Patient-Oriented Eczema Measure (POEM) and in the Dermatology Life Quality Index (DLQI) all showed statistically significant differences between the vehicle and both M610101 groups, with the 1.5% M610101 group showing greater improvements compared to the 0.75% M610101 group on every assessment day. - The PP-NRS and SD-NRS on each day improved over time from Day 2 to Day 15 in both M610101 groups. In the 1.5% M610101 group, the PP-NRS and the SD-NRS on each day were significantly improved compared with those in the 0.75% M610101 group on all assessment days.

When 1.5% or 0.75% M610101 was administered twice daily to atopic dermatitis patients for 8 weeks, both M610101 groups demonstrated superiority to the vehicle group, and the safety was acceptable.

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2031220567

Tomoyuki Nishiura

Maruho Co.,Ltd. Kyoto R&D Center

93 chudoji Awatacho, Shimogyo-ku, Kyoto

ctinfo@mii.maruho.co.jp

Clinical Trials Information -

Maruho Co.,Ltd. Kyoto R&D Center

93 chudoji Awatacho, Shimogyo-ku, Kyoto

+81-75-325-3279

ctinfo@mii.maruho.co.jp

Complete

Jan. 12, 2023

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

Patients with atopic dermatitis over 12 years old

Patients with an IGA score of 2 or 3 for atopic dermatitis

Patients complicated with diseases considered inappropriate for participation in clinical trials such as serious cardiac / hepatic / renal / pulmonary / hematologic disease

Patients with skin diseases other than atopic dermatitis that affect the evaluation of atopic dermatitis or the safety of the subject

Both

Atopic dermatitis

M6101:0.75% or 1.5% BID
placebo:BID

Proportion of participants achieving IGA score of 0 or 1 with improvement from baseline at week 8

+81-3-3881-6116

Dec. 15, 2022

none