Efficacy and Safety of Roflumilast Cream in Subjects With Atopic Dermatitis

A Phase 3 Multicenter, Double-blind, Vehicle-controlled Brigding Study to Evaluate the Efficacy and Safety of Roflumilast Cream 0.15% (ZORYVE®) in the Treatment of Patients With Mild to Moderate Atopic Dermatitis

This study will assess the safety and efficacy of Roflumilast cream versus vehicle applied once a day for 4 weeks by subjects with atopic dermatitis.

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis (AD)
• Intervention / Treatment: Drug: Roflumilast Cream 0.15%; Drug: Vehicle cream

Detailed Description

This is a parallel group, double blind, vehicle-controlled study in which Roflumilast cream or vehicle is applied once daily for 4 weeks to subjects with mild or moderate atopic dermatitis.

• Study Type: Interventional
• Enrollment (Actual): 354
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Wuhu, Anhui, China
      • The Second Affiliated Hospital of Wannan Medical College
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Beijing Aerospace General Hospital
    • Beijing, Beijing Municipality, China
      • Beijing Children's Hospital
    • Beijing, Beijing Municipality, China
      • Beijing Tongren Hospital, CMU
    • Beijing, Beijing Municipality, China
      • Beijing Tsinghua Changgung Hospital
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China
      • Chongqing Medical University Affiliated Second Hospital
    • Chongqing, Chongqing Municipality, China
      • People's Hospital Affiliated to Chongqing Three Gorges Medical College
  • Fujian
    • Fuzhou, Fujian, China
      • Fujian Medical University Union Hospital
    • Xiamen, Fujian, China
      • The Second Affiliated Hospital of Xiamen medical college
  • Guangdong
    • Dongguan, Guangdong, China
      • Dongguan People's Hospital
    • Dongguan, Guangdong, China
      • The Sixth People's Hospital of Dongguan
    • Guangzhou, Guangdong, China
      • The Second Affiliated Hospital of Guangzhou Medical University
    • Guangzhou, Guangdong, China
      • Dermatology Hospital of Southern Medical University
    • Shenzhen, Guangdong, China
      • Shenzhen Children's Hospital
    • Shenzhen, Guangdong, China
      • Union Shenzhen Hospital
  • Guangxi
    • Liuzhou, Guangxi, China
      • Liuzhou People's Hospital
  • Hainan
    • Haikou, Hainan, China
      • Hainan General Hospital
    • Haikou, Hainan, China
      • The Fifth People's Hospital of Hainan Province
    • Kunming, Hainan, China, China
      • Kunming Children's hospital
  • Hebei
    • Shijiazhuang, Hebei, China
      • Shijiazhuang People's Hospital
    • Shijiazhuang, Hebei, China
      • TCM Hospital of Shi Jia Zhuang City
    • Xingtai, Hebei, China
      • Xingtai People's Hospital
  • Henan
    • Luoyang, Henan, China
      • The Second Hospital affiliated to Henan University of Science and Technology
    • Nanyang, Henan, China
      • Nanyang Central Hospital
    • Sanmenxia, Henan, China
      • Sanmenxia Central Hospital
    • Zhengzhou, Henan, China
      • Zhengzhou Central Hospital
    • Zhengzhou, Henan, China
      • Henan Children's Hospital Zhengzhou Children's Hospital
  • Hubei
    • Jingzhou, Hubei, China
      • Jingzhou Central Hospital
    • Wuhan, Hubei, China
      • Renmin Hospital of Wuhan University
    • Yichang, Hubei, China
      • Yichang Central People's Hospital
  • Hunan
    • Changde, Hunan, China
      • The First People's Hospital of Changde City
    • Changsha, Hunan, China
      • Hunan Children's Hospital
    • Changsha, Hunan, China
      • The second Xiangya Hospital of Central South University
    • Changsha, Hunan, China
      • Xiangya Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Sir Run Run Hospital Nanjing Medical University
    • Wuxi, Jiangsu, China
      • Wuxi Second People's Hospital
    • Wuxi, Jiangsu, China
      • J.Y Hospital of TCM
    • Wuxi, Jiangsu, China
      • People's hospital of Wuxi
    • Zhenjiang, Jiangsu, China
      • Affiliated Hospital of Jiangsu University
  • Jiangxi
    • Nanchang, Jiangxi, China
      • The Second Affiliated Hospital of Nanchang University
    • Nanchang, Jiangxi, China
      • Dermatology Hospital of Jiangxi Province
  • Jilin
    • Changchun, Jilin, China
      • The First Bethune Hospital of Jilin University
  • Liaoning
    • Dalian, Liaoning, China
      • Dalian Municipal Women and Children's Medical Center
    • Dalian, Liaoning, China, China
      • Dalian Dermatology Hospital
    • Panjin, Liaoning, China
      • Panjin Liaohe Oilfield Gem Flower Hospital
  • Neimenggu
    • Baotou, Neimenggu, China
      • The First affiliated Hospital of Baotou College
  • Shandong
    • Jinan, Shandong, China
      • Jinan Central Hospital
    • Jinan, Shandong, China
      • Qilu Hospital of Shandong University
    • Liaocheng, Shandong, China
      • Liaocheng People's Hospital
    • Qingdao, Shandong, China
      • Hiser Medical Center of Qingdao
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Huashan Hospital, Fudan University
    • Shanghai, Shanghai Municipality, China
      • Shanghai Children's Hospital
  • Shanxi
    • Xi’an, Shanxi, China
      • The Second Affiliated Hospital of Xi'an Jiaotong University
  • Sichuan
    • Chengdu, Sichuan, China
      • Chengdu Women's and Children's Central Hospital
    • Chengdu, Sichuan, China
      • Chengdu Second People's Hospital
    • Chengdu, Sichuan, China
      • Sichuan Academy of Medical Sciences - Sichuan Provincial People's Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Hangzhou First People's Hospital
    • Jiaxing, Zhejiang, China
      • The First Hospital of Jiaxing
    • Jiaxing, Zhejiang, China
      • The Second Hospital of Jiaxing
    • Ningbo, Zhejiang, China
      • The Second Hospital of Ningbo
    • Taizhou, Zhejiang, China
      • Taizhou Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female subjects aged ≥ 6 years at screening.
2. Diagnosed with atopic dermatitis (AD) for at least 6 months for subjects aged ≥18 years and 3 months for subjects aged 6~17 years at screening.
3. Have stable disease for the past 4 weeks prior to screening.
4. Have mild or moderate AD at baseline.
5. Have BSA affected by AD of 3%-20% at baseline.
6. Women of childbearing potential (WOCBP) have a negative pregnancy blood test at screening and a negative urine pregnancy test at baseline. WOCBP must have taken and agree to continue taking highly effective contraceptive measures from 4 weeks before the first dose to 2 months after the last dose.
7. Being in good health as judged by the Investigator.
8. Subjects voluntarily participate in the study and sign the ICF before the start of study-related activities.

Exclusion Criteria:

1. Subjects with any serious medical condition or clinically significant abnormality that would prevent study participation or place the subject at significant risk, as judged by the Investigator.
2. Previous treatment with roflumilast cream.
3. Use of systemic treatments that affect the efficacy assessment of AD 4 weeks or 5 half-lives (whichever is longer) prior to the first dose.
4. Use of topical treatments that affect the efficacy assessment of AD 2 weeks prior to the first dose.
5. Use of phototherapy, tanning beds, or any other light-emitting devices within 4 weeks prior to the first dose.
6. Female subjects who are pregnant or breastfeeding, or plan to become pregnant or breastfeed during the study.
7. Subjects with a history of chronic alcohol or drug abuse within 6 months prior to Screening.
8. Subjects who are family members of the clinical study site, clinical study staff, or sponsor, or family members of enrolled subjects living in the same house.
9. Subjects/legal guardians who are unable to communicate, understand the study, or other situations deemed inappropriate for participation in a clinical trial by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Vehicle cream; Placebo comparator	Drug: Vehicle cream; Vehicle cream is applied once daily for 4 weeks
Experimental: Roflumilast cream 0.15%; Active comparator	Drug: Roflumilast Cream 0.15%; Roflumilast cream 0.15% is applied once daily for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of subjects with vIGA-AD success	The vIGA-AD is a static evaluation of qualitative overall AD severity. This global assessment scale is an ordinal scale with five severity grades (reported only in integers of 0 to 4 where 0 is clear). IGA sucess is defined as a vIGA-AD score of 'clear' or 'almost clear' plus at least 2-grade improvement from baseline	Baseline, week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In subjects with moderate AD severity (vIGA-AD score of 3) at baseline, percentage of subjects with vIGA-AD success	The vIGA-AD is a static evaluation of qualitative overall AD severity. This global assessment scale is an ordinal scale with five severity grades (reported only in integers of 0 to 4 where 0 is clear).	Baseline, week 4
Percentage of subjects with vIGA-AD of "clear" or "almost clear"	The vIGA-AD is a static evaluation of qualitative overall AD severity. This global assessment scale is an ordinal scale with five severity grades (reported only in integers of 0 to 4 where 0 is clear).	Baseline, week 4
In subjects with WI-NRS ≥ 4 at baseline, percentage of subjects with ≥ 4 point reduction in WI-NRS	The Worst Itch Numerical Rating Scale (WI-NRS) will be determined by the subject's recording of daily assessment of worst itch over the past 24 hours. The scale is from '0 to 10' ("no itch" to "worst itch imaginable" or "worst imaginable itch").	Baseline, week 4
Percentage of subjects with at least 75% reduction in the Eczema Area and Severity Index (EASI-75)	EASI combines the assessment of the severity of lesions and the area affected into a single total score in the range 0 (no disease) to 72 (maximal disease). Four anatomic sites-head, upper extremities, trunk, and lower extremities-are assessed for erythema, induration/infiltration (papules), excoriation, and lichenification as seen on the day of the examination. To calculate the EASI, the sum of the severity rating (0 to 3 with 3 being the most severe) for four clinical signs are multiplied with the numerical value of the area affected and with the percentage of the four body areas.	Baseline, week 4
Safety: treatment emergence adverse events	Incidence, severity, and causal relationship of treatment emergence adverse events (TEAE), TEAEs leading to withdrawal and death.	Up to 4 weeks
Trough concentration (Ctrough)	Trough concentration of plasma roflumilast and its N-oxide	Week 2, week 4

Collaborators and Investigators

• Sponsor: Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2024
• Primary Completion (Actual): May 27, 2025
• Study Completion (Actual): July 13, 2025

Study Registration Dates

• First Submitted: September 30, 2024
• First Submitted That Met QC Criteria: October 4, 2024
• First Posted (Actual): October 8, 2024

Study Record Updates

• Last Update Posted (Estimated): September 2, 2025
• Last Update Submitted That Met QC Criteria: August 29, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Atopic dermatitis; Roflumilast cream
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Skin Diseases; Skin Diseases, Genetic; Skin Diseases, Eczematous; Dermatitis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Dermatitis, Atopic
• Other Study ID Numbers: HDM3014-2-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes