A Study to Evaluate the Effectiveness and Safety of Topical OPA-15406 Ointment to Treat Participants With Atopic Dermatitis

A Phase 2 Multi-center, Randomized, Double-blind, Vehicle-controlled, Three-arm, Parallel Group Study to Assess the Safety, Tolerability, and Efficacy of Topical OPA-15406 Ointment, in Subjects With Mild/Moderate Atopic Dermatitis

The purpose of this study is to investigate the effectiveness and safety of 2 concentrations of OPA-15406 compared to vehicle in participants with atopic dermatitis (AD).

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: OPA-15406; Drug: Vehicle ointment

Detailed Description

AD is a disease mainly characterized by pruritic eczema, and those with the disease experience repeated exacerbations and remissions. Therapeutic guidelines for the disease, currently being developed in many countries, all recognize AD as chronic eczema that is accompanied by the physiological dysfunction of the skin and in which inflammation is caused by various nonspecific stimuli or specific allergens. OPA 15406 is a type-4 phosphodiesterase (PDE4) inhibitor. PDE4 inhibitors are thought to be useful for allergic inflammatory diseases. This is a Phase 2 dose ranging study to evaluate the efficacy of two concentrations of OPA 15406 ointment compared to vehicle, when administered topically twice daily in participants with mild to moderate AD.

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Phillip, Australian Capital Territory, Australia
  • New South Wales
    • Kogarah, New South Wales, Australia
  • Queensland
    • Woolloongabba, Queensland, Australia
  • South Australia
    • Hectorville, South Australia, Australia, 5073
  • Western Australia
    • Fremantle, Western Australia, Australia
• Poland
  • Katowice, Poland
  • Krakow, Poland
  • Lodz, Poland
  • Warsaw, Poland
  • Wroclaw, Poland
• United States
  • California
    • Los Angeles, California, United States, 90045
    • San Diego, California, United States, 92123
  • Colorado
    • Denver, Colorado, United States, 80220
  • Florida
    • Orange Park, Florida, United States, 32065
    • Tampa, Florida, United States, 33613
    • West Palm Beach, Florida, United States, 33401
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
  • Indiana
    • Carmel, Indiana, United States, 46032
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
  • New Jersey
    • Verona, New Jersey, United States, 07044
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
  • New York
    • Stony Brook, New York, United States, 11790
  • North Carolina
    • High Point, North Carolina, United States, 27262
  • Oregon
    • Portland, Oregon, United States, 97239-4501
  • Texas
    • Austin, Texas, United States, 78759
    • College Station, Texas, United States, 77845
    • Houston, Texas, United States, 77065
    • San Antonio, Texas, United States, 78229
  • Virginia
    • Norfolk, Virginia, United States, 23507
  • Washington
    • Spokane, Washington, United States, 99204

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants 10-70 years of age
• Diagnosis of AD
• History of AD for at least 3 years
• AD affecting greater than or equal to 5% and less than or equal to 40% of total body surface area (BSA) at Baseline
• Investigator's Global Assessment of Disease Severity score of 2 (mild) or 3 (moderate) in the selected treatment area(s)

Exclusion Criteria:

• Contact or atopic dermatitis flare within 28 days of the Baseline (Day 1) visit.
• Concurrent diseases/conditions and history of other diseases/conditions in the selected treatment area(s) that may have an impact on the study assessments.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.3% OPA-15406; OPA-15406 0.3% ointment was applied topically twice daily (BID) to the selected treatment area(s) at approximately 12-hour intervals for 8 weeks.	Drug: OPA-15406; OPA-15406 topical ointment
Experimental: 1% OPA-15406; OPA-15406 1% ointment was applied topically BID to the selected treatment area(s) at approximately 12-hour intervals for 8 weeks.	Drug: OPA-15406; OPA-15406 topical ointment
Placebo Comparator: Vehicle Ointment; OPA-15406 1%-matching placebo (vehicle ointment) was applied topically BID to the selected treatment area(s) at approximately 12-hour intervals for 8 weeks.	Drug: Vehicle ointment; OPA-15406 1%-matching placebo topical ointment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Success in the Overall Investigator's Global Assessment of Disease Severity (IGA) Score at Week 4 [Using Non-responder Imputation or Last Observation Carried Forward (LOCF)]	The IGA evaluation was performed by a certified rater. The IGA score, used to assess the overall disease severity, consists of a 6-point severity scale from clear to very severe disease (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe disease, and 5 = very severe disease). The IGA uses clinical characteristics of erythema, infiltration, papulation, oozing, and crusting as guidelines for the overall severity assessment. The IGA assessment was performed for the overall selected treatment area(s): overall percentage body surface area to be treated and additionally for the target lesion. Success was defined as a score of 0 or 1 with at least a 2-grade reduction from Baseline. Participants without IGA score at Week 4 were treated as non-responders. In the sensitivity analysis, missing IGA score at Week 4 was imputed using LOCF method first and the success was defined based on the imputed IGA score.	Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Overall IGA Score at Week 4 [Using Mixed Model Repeated Measures (MMRM) Analysis]	The IGA evaluation was performed by a certified rater. The IGA allows for an assessment of overall disease severity at a given time point, and it consists of a 6-point severity scale from clear to very severe disease (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe disease, and 5 = very severe disease). The IGA uses clinical characteristics of erythema, infiltration, papulation, oozing, and crusting as guidelines for the overall severity assessment. The IGA assessment was performed for the overall selected treatment area(s): overall percentage body surface area to be treated and additionally for the target lesion. A negative change from Baseline indicates improvement in overall IGA score.	Baseline, Week 4
Change From Baseline in Overall IGA Score at Week 4 [Using Last Observation Carried Forward (LOCF) Analysis]	The IGA allows for an assessment of overall disease severity at a given time point, and it consists of a 6-point severity scale from clear to very severe disease (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe disease, and 5 = very severe disease). The IGA uses clinical characteristics of erythema, infiltration, papulation, oozing, and crusting as guidelines for the overall severity assessment. Missing overall IGA scores at Week 4 were imputed using LOCF method. A negative change from Baseline indicates improvement in overall IGA score.	Baseline, Week 4
Percentage of Participants With Adverse Events (AEs)	An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An serious adverse event (SAE) was defined as any event which resulted in death, was life-threatening, was a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, required in-patient hospitalization or prolonged hospitalization, was a congenital anomaly/birth defect, or was another medically significant event.	From signing of informed consent through Week 8

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Success in the Overall IGA Score at Week 8 (Using Non-responder Imputation or LOCF Imputation)	IGA evaluation was performed by a certified rater. The IGA consists of a 6-point severity scale from clear to very severe disease (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe disease, and 5 = very severe disease). The IGA uses clinical characteristics of erythema, infiltration, papulation, oozing, and crusting as guidelines for the overall severity assessment. The IGA assessment was performed for the overall selected treatment area(s): overall percentage body surface area to be treated and additionally for the target lesion. Success was defined as a score of 0 or 1 with at least a 2-grade reduction from Baseline. In the primary analysis, participants without IGA score available at Week 8 were treated as non-responders. In the sensitivity analysis, the missing IGA score at Week 8 was imputed using LOCF method first and the success was defined based on the imputed IGA score.	Week 8
Change From Baseline in Eczema Area and Severity Index (EASI) Score (Using MMRM Analysis)	The EASI evaluation assesses the extent of disease at 4 body sites and measures 4 clinical signs: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each on a scale from 0 (no disease) to 3 (very severe). The EASI scale allows for a maximum score of 72. The EASI assessment was performed on overall body. A negative change from Baseline indicates improvement in EASI score.	Baseline, Weeks 4 and 8
Change From Baseline in EASI Score (Using LOCF Analysis)	The EASI evaluation assesses the extent of disease at 4 body sites and measures 4 clinical signs: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each on a scale from 0 (no disease) to 3 (very severe). The EASI scale allows for a maximum score of 72. The EASI assessment was performed on overall body. A negative change from Baseline indicates improvement in EASI score.	Baseline, Weeks 4 and 8
Change From Baseline in Visual Analog Scale (VAS) Score for Pruritus (Using MMRM Analysis)	At each evaluation, the participants were asked to record their current pruritus intensity over their body overall, not just within the selected treatment areas[s] (i.e., intensity over the last 24 hours) on a horizontal 100-mm line marked as "No itch" on the left end and "Worst imaginable itch" on the right end. The VAS assessment was performed on the overall impression of itch on the body and not just for the selected treatment area(s) or for the target lesion. A negative change from Baseline indicates improvement in VAS score.	Baseline, Weeks 4 and 8
Change From Baseline in VAS for Pruritus (Using LOCF Analysis)	At each evaluation, the participants were asked to record their current pruritus intensity over their body overall, not just within the selected treatment areas[s] (i.e., intensity over the last 24 hours) on a horizontal 100-mm line marked as "No itch" on the left end and "Worst imaginable itch" on the right end. The VAS assessment was performed on the overall impression of itch on the body and not just for the selected treatment area(s) or for the target lesion. A negative change from Baseline indicates improvement in VAS score.	Baseline, Weeks 4 and 8

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2014
• Primary Completion (Actual): January 28, 2015
• Study Completion (Actual): February 3, 2015

Study Registration Dates

• First Submitted: February 19, 2014
• First Submitted That Met QC Criteria: February 20, 2014
• First Posted (Estimate): February 21, 2014

Study Record Updates

• Last Update Posted (Actual): November 23, 2021
• Last Update Submitted That Met QC Criteria: October 25, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Atopic Dermatitis, Eczema
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: 271-12-205; 2013-003899-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
• IPD Sharing Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
• IPD Sharing Access Criteria: Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No