Phase 2 Study of OPA-15406 Ointment in Pediatric Patients With Atopic Dermatitis

Study Overview
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Brief Summary
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To evaluate the safety, efficacy (dose response) and pharmacokinetics of 0.3% and 1% OPA-15406 when applied twice daily for 4 weeks in pediatric patients with atopic dermatitis.

Official Title
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A Multicenter, Randomized, Double-blind, Vehicle-controlled, Parallel-group Trial to Assess the Safety and Efficacy of 0.3% and 1% OPA-15406 Ointments When Administered for 4 Weeks in Pediatric Patients With Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: OPA-15406
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of atopic dermatitis based on the criteria of Hanifin and Rajka Exclusion Criteria: Subjects who have an atopic dermatitis or contact dermatitis flare-up defined as a sudden intensification of atopic dermatitis. Subjects who have an active viral skin infection. Subjects with a current or history of malignancy.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.3% OPA-15406 Ointments<br>Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. | Drug: OPA-15406<br> <br> |
| Experimental: 1% OPA-15406 Ointments<br>Subjects were treated with assigned 1% OPA-15406 ointment twice daily. | Drug: OPA-15406<br> <br> |
| Placebo Comparator: Placebo Ointments<br>Subjects were treated with assigned 0% OPA-15406 ointment twice daily. | Drug: Placebos<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Subjects Experiencing AEs | The number of subjects experiencing AEs will be calculated for each treatment group. Treatment-emergent adverse events (TEAEs) occurring after the start of IMP administration are summarized. The number of subjects with events, the number of events is obtained for all the TEAEs reported. | Week 0-4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder Rate of Investigator's Global Assessment(IGA) of Disease Severity at Week4 | The investigator or subinvestigator assessed the skin symptoms using IGA. The investigator or subinvestigator scored the severity (0 = clear, 1 = almost clear, 2 =mild, 3 = moderate, 4 = severe/very severe) of the overall symptoms of the treatment area (erythema, infiltration, papules, effusion and scab formation) from baseline to Week4. Incidence of success in IGA was defined as the rate of subjects whose IGA score was 0 (clear) or 1 (almost clear) and had improved by at least 2 grades (responders) from baseline. | Baseline and Week 4 | 
| Change From Baseline in Eczema Area and Severity Index (EASI) Score | The investigator or sub investigator assessed the symptoms of AD using EASI. EASI's minimum and maximum scores are 0 and 72 scores respectively. The higher the EASI score is, the more severe the symptoms of AD, and a negative change from the baseline means improvement and a positive change means worsening. The investigator or sub investigator scored the severity (0-3 points) and affected BSA (%) based on the 4 symptoms (erythema, infiltration/papules, excoriation, and lichenification) on the 4 body regions (face, neck and head ; upper limbs ;; and lower limbs). Number of participants analyzed represents number of participants with data at both Baseline and Week4. Participants who have no data were excluded. | Baseline, Week 4 | 
| Change From Baseline in Visual Analogue Scale(VAS) for Pruritus Score | The investigator or subinvestigator evaluated the level of pruritus based on VAS. The subjects aged 7 to 14 years old marked the point of pruritus intensity during the last 24 hours on a 0 to 100mm VAS, with 0 being no pruritis to 100 being very severe pruritis.For subjects aged 2 to 6 years, this would not be evaluated. The negative value showed the degree of improvement. | Baseline, Week 4 | 
| Change From Baseline in Verbal Rating Scale(VRS) for Pruritus Score | The investigator or subinvestigator evaluated the pruritus intensity based on VRS. The subjects aged 7 to 14 years old evaluated the pruritus intensity according to the following criteria. The subjects recorded the level of pruritus and the time and date of evaluation in a pruritus diary. 0 : None : Mild : Moderate : Severe For subjects aged 2 to 6 years, this would not be evaluated. The negative value showed the degree of improvement. | Baseline, Hour 156 | 
| Change From Baseline in Patient-Oriented Eczema Measure(POEM) Score | The investigator or sub investigator evaluated eczema according to the POEM. The subjects answered 7 questions about their eczema by 0-4 points per question. The POEMS's minimum and maximum scores are 0 and 28 scores respectively. The higher the POEM score is, the more severe the symptoms are, and a negative change from the baseline means improvement and a positive change means worsening. If it is difficult for subjects to answer the questions, their parents answered them instead. Number of participants analyzed represents number of participants with data at both Baseline and Week4. Participants who have no data were excluded. | Baseline, Week 4 | 
| Change From Baseline in Percentage Affected Body Surface Area | The investigator or subinvestigator drew the affected BSA (range of skin eruption at the time of examination) on the human body drawing to determine the affected areas (%) on the respective 4 body regions (face, neck, and head; upper limbs; trunk; and lower limbs). One palm of the subject corresponds to 1% BSA. The negative value showed the degree of improvement. | Baseline, Week 8, 16, 24 | 
| Mean (SD) OPA-15406 Plasma Trough Concentrations at week1 | The plasma concentration of OPA-15406 was measured at Week 1. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration. | Week 1 | 
| Mean (SD) OPA-15406 Plasma Trough Concentrations at week4 | The plasma concentration of OPA-15406 was measured at Week 4. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration. | week4 | 
| Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA at week1 | The plasma concentration of OPA-15406 was measured at Week 1. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.Each plasma concentration was normalized by dose. | week1 | 
| Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA at week4 | The plasma concentration of OPA-15406 was measured at Week 4. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.Each plasma concentration was normalized by dose. | week4 |