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A Phase III Long-Term Study of M610101 in Patients with Atopic Dermatitis

A Phase III Long-Term Study of M610101 in Patients with Atopic Dermatitis

331

In the full analysis set (FAS), the demographic and other baseline characteristics were generally similar across the treatment groups. Overall, there were more males, with 221 males (66.8%) and 110 females (33.2%). The mean (SD) values for age, weight, and duration of atopic dermatitis were 33.3 (12.1) years, 64.97 (12.59) kg, and 22.73 (13.26) years, respectively. As for Investigator's Global Assessment (IGA) score, 101 participants (30.5%) had an IGA score of 2 (Mild), and 230 participants (69.5%) of 3 (Moderate). As for Eczema Area and Severity Index (EASI) score, the mean (SD) was 9.523 (4.197), with 102 participants (30.8%) having an EASI score of <=7 and 229 participants (69.2%) having an EASI score of >7. The mean (SD) percentage of Body Surface Area (%BSA) was 14.65% (4.60%), with 58 participants (17.5%) having a %BSA of <10% and 273 participants (82.5%) having a %BSA of >=10%.

Out of the 367 enrolled participants, 331 (0.75% M610101 group: 165, 1.5% M610101 group: 166 [in the same order thereafter]) were randomized*, and all received the study drug. Among the 165 participants in the 0.75% M610101 group, the rollover participants were 14 (10 from the 0.75% M610101 group and 4 from the vehicle group in Study M610101-01), and the new participants were 151. Similarly, among the 166 participants in the 1.5% M610101 group, 11 rollover participants (10, 1, respectively) and 155 new participants. The participants who were not randomized were 36. A total of 274 participants (126, 148, respectively) completed the study, of which 252 participants (116, 136, respectively) completed Week 52, and 22 participants (10, 12, respectively) met the completion criteria. A total of 57 participants (39, 18, respectively) discontinued the study. A total of 315 participants (155, 160, respectively) transitioned to the follow-up visit and a total of 11 participants (6, 5, respectively) did not transition to the follow-up visit. *Among the rollover participants, those who received the M610101 in Study M610101-01 (jRCT2031220567) were allocated to the same concentration group as in Study M610101-01 in Study M610101-02 (this study).

- The safety analysis set included 331 participants (164 in the 0.75% M610101 group; 167 in the 1.5% M610101 group). - The incidence of adverse events (AEs) was 90.9% (149 of 164) in the 0.75% M610101 group and 83.2% (139 of 167) in the 1.5% M610101 group (same order thereafter), respectively. Of these, the incidence of AEs related to the study drug was 26.2% (43 of 164) and 21.6% (36 of 167), respectively, with the incidence of AEs, regardless of their relation to the study drug, being similar in both groups. The incidence of severe AEs of Grade 3 or higher was low at 3.0% in both groups, with most AEs being of Grade 1 or Grade 2 severity. - Among the common AEs, the most frequently observed AE in the 0.75% M610101 group was nasopharyngitis, followed by COVID-19, acne and dermatitis atopic. The most frequently observed AE in the 1.5% M610101 group was also nasopharyngitis, followed by acne, influenza and COVID-19. The common AEs were similar between the two groups. - In both groups, regardless of the relation to the study drug, the incidence of AEs (first occurrence) was highest from Day 1 to Day 84, and there was no trend of increasing incidence over the course of the treatment period. Furthermore, there were no specific AEs in either group that showed an increased incidence over the course of the treatment. - No AEs leading to death occurred. Other serious AEs occurred in 6 participants in the 0.75% M610101 group and in 3 participants in the 1.5% M610101 group. The severity was Grade 4 (suicide attempt), Grade 3 (Hodgkin's disease, salivary gland calculus, rhabdomyolysis, femur fracture, stress, gastroenteritis, and pancreatitis acute) or Grade 2 (rhegmatogenous retinal detachment, and atrial fibrillation). All were unrelated to the study drug. - The incidence of AEs requiring withdrawal, dose reduction, or interruption of the study drug was similar in both groups, 22.6% (37 of 164) in the 0.75% M610101 group and 19.8% (33 of 167) in the 1.5% M610101 group. Of these, the incidence of AEs related to the study drug was 12.8% (21 of 164) in the 0.75% M610101 group and 5.4% (9 of 167) in the 1.5% M610101 group, indicating a higher incidence in the 0.75% M610101 group compared to the 1.5% M610101 group. - Among AEs of special interest, the incidence of cytopenias was 3.0% (5 of 164) in the 0.75% M610101 group and 6.6% (11 of 167) in the 1.5% M610101 group (same order thereafter), with the 1.5% M610101 group showing a higher incidence compared to the 0.75% M610101 group. The incidence of infections (including herpes zoster and skin infections) was 62.8% (103 of 164) and 62.3% (104 of 167), respectively, which was similar across both groups. Of these, the incidence of AEs related to the study drug was 9.8% (16 of 164) and 5.4% (9 of 167), respectively, with the 0.75% M610101 group showing a higher incidence compared to the 1.5% M610101 group. The cytopenias and infections (including herpes zoster and skin infections) observed in this study could be anticipated as the 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 electrocardiograms.

- All 331 participants who were randomized and received the study drug (165 in the 0.75% M610101 group; 166 in the 1.5% M610101 group) were included in the FAS. - The participants of this study were patients with atopic dermatitis with an IGA score of 2 or 3. The proportion of participants with an IGA score of 1 or less increased generally over time until Week 52 in both groups. The proportion of participants with an IGA score of 2 increased in both groups at Week 2 and then generally decreased over time until Week 52. The proportion of participants with an IGA score of 3 decreased in both groups at Week 2, with no significant fluctuations thereafter until Week 52. The proportion of participants with an IGA score of 4 was low and 2 or fewer participants in both groups throughout the treatment period. - Mean percent change in EASI decreased at Week 2 in the 0.75% M610101 group, and then remained at similar levels to that of Week 2 until Week 52. Furthermore, in the 1.5% M610101 group, it decreased over time from Week 2 to Week 4, and then remained at similar levels to that of Week 4 until Week 52. The 1.5% M610101 group showed greater improvement in EASI compared to the 0.75% M610101 group on all evaluation days. - Mean change in the representative value of Peak Pruritus Numerical Rating Scale (PP-NRS) decreased over time from Week 1 to Week 2 in both groups, and then remained at similar levels to that of Week 2 until Week 52. The 1.5% M610101 group showed greater improvement in PP-NRS compared to the 0.75% M610101 group on all evaluation days. - Mean change in the representative value of Sleep Disturbance-Numerical Rating Scale (SD-NRS) decreased over time from Week 1 to Week 2 in both groups, and then remained at similar levels to that of Week 2 until Week 52. The 1.5% M610101 group showed greater improvement in SD-NRS compared to the 0.75% M610101 group on all evaluation days. - Mean change in Patient-Oriented Eczema Measure (POEM) scores was observed to decrease at Week 4 in both groups, and then remained at similar levels until Week 52. - Mean changes in Dermatology Life Quality Index (DLQI) and Children's DLQI (CDLQI) scores were observed to decrease at Week 4 in both groups, and then remained at similar levels until Week 52. - The proportion of participants who achieved the IGA score of 0 or 1 with an IGA score improvement of 2 or more grades from baseline increased at Week 2 in the 0.75% M610101 group, and then generally increased over time until Week 52. In the 1.5% M610101 group, after this proportion increased over time from Week 2 to Week 4, it generally remained at similar levels to that of Week 4 until Week 44, and then increased until Week 52. The proportion of participants who achieved the IGA score of 0 or 1 with an IGA score improvement of 2 or more grades from baseline was higher in the 1.5% M610101 group compared to the 0.75% M610101 group on all evaluation days except for Week 2 and Week 32. - The proportion of participants who achieved an improvement of 75% or more in EASI increased at Week 2 in the 0.75% M610101 group, and then generally remained at similar levels to that of Week 2 until Week 52. In the 1.5% M610101 group, this proportion increased over time from Week 2 to Week 4, and then generally remained at similar levels to that of Week 4 until Week 52. The proportion of participants who improved 75% or more in EASI was higher in the 1.5% M610101 group compared to the 0.75% M610101 group on all evaluation days except for Week 2 and Week 32.

The safety of applying 0.75% or 1.5% M610101 twice daily for a long period (up to 52 weeks) in patients with atopic dermatitis was confirmed to be acceptable. Furthermore, it was demonstrated that both concentrations improve the symptoms of atopic dermatitis at an early stage, and the effects are sustained over a long period. The degree of symptom improvement was greater in the 1.5% M610101 group compared to the 0.75% M610101 group.

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2031220566

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

uncontrolled control

single 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

Safety after long-term application of M610101 (up to 52 weeks)
(adverse events, laboratory tests, vital signs, ECG)

+81-3-3881-6116

Dec. 15, 2022

none