Trial Outcomes & Findings for Phase 2 Study of OPA-15406 Ointment in Pediatric Patients With Atopic Dermatitis (NCT NCT03018691)

NCT ID: NCT03018691

Last Updated: 2020-07-23

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 73 participants
• Primary outcome timeframe: Week 0-4
• Results posted on: 2020-07-23

Participant Flow

Participant milestones

Measure	0.3% OPA-15406 Ointments Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406	1% OPA-15406 Ointments Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406	Placebo Ointments Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos
Overall Study STARTED	24	25	24
Overall Study COMPLETED	22	24	17
Overall Study NOT COMPLETED	2	1	7

Reasons for withdrawal

Measure	0.3% OPA-15406 Ointments Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406	1% OPA-15406 Ointments Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406	Placebo Ointments Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos
Overall Study Adverse Event	1	1	4
Overall Study Lack of Efficacy	0	0	1
Overall Study Withdrawal by Subject	0	0	1
Overall Study Withdrawal by parent/guardian	1	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	0.3% OPA-15406 Ointments n=24 Participants Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406	1% OPA-15406 Ointments n=25 Participants Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406	Placebo Ointments n=24 Participants Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos	Total n=73 Participants Total of all reporting groups
Age, Categorical <=18 years	24 Participants n=5 Participants	25 Participants n=7 Participants	24 Participants n=5 Participants	73 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	8.5 years STANDARD_DEVIATION 3.8 • n=5 Participants	7.9 years STANDARD_DEVIATION 3.5 • n=7 Participants	8.5 years STANDARD_DEVIATION 3.1 • n=5 Participants	8.3 years STANDARD_DEVIATION 3.4 • n=4 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	10 Participants n=7 Participants	5 Participants n=5 Participants	21 Participants n=4 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	15 Participants n=7 Participants	19 Participants n=5 Participants	52 Participants n=4 Participants
Race/Ethnicity, Customized Japanese Subjects	24 participants n=5 Participants	25 participants n=7 Participants	24 participants n=5 Participants	73 participants n=4 Participants
Region of Enrollment Japan	24 Participants n=5 Participants	25 Participants n=7 Participants	24 Participants n=5 Participants	73 Participants n=4 Participants

PRIMARY outcome

Timeframe: Week 0-4

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.

Outcome measures

Measure	0.3% OPA-15406 Ointments n=24 Participants Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406	1% OPA-15406 Ointments n=25 Participants Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406	Placebo Ointments n=24 Participants Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos
The Number of Subjects Experiencing AEs	11 participants	14 participants	12 participants

SECONDARY outcome

Timeframe: Baseline and Week 4

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.

Outcome measures

Measure	0.3% OPA-15406 Ointments n=24 Participants Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406	1% OPA-15406 Ointments n=25 Participants Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406	Placebo Ointments n=24 Participants Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos
Responder Rate of Investigator's Global Assessment(IGA) of Disease Severity at Week4	37.50 Percentage of participants Interval 18.8 to 59.41	40.00 Percentage of participants Interval 21.13 to 61.33	8.33 Percentage of participants Interval 1.03 to 27.0

SECONDARY outcome

Timeframe: Baseline, Week 4

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.

Outcome measures

Measure	0.3% OPA-15406 Ointments n=23 Participants Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406	1% OPA-15406 Ointments n=24 Participants Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406	Placebo Ointments n=18 Participants Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos
Change From Baseline in Eczema Area and Severity Index (EASI) Score	-5.33 score on a scale Standard Error 1.28	-5.52 score on a scale Standard Error 1.26	0.56 score on a scale Standard Error 1.36

SECONDARY outcome

Timeframe: Baseline, Week 4

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.

Outcome measures

Measure	0.3% OPA-15406 Ointments n=16 Participants Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406	1% OPA-15406 Ointments n=16 Participants Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406	Placebo Ointments n=14 Participants Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos
Change From Baseline in Visual Analogue Scale(VAS) for Pruritus Score	-18.00 mm Standard Error 7.27	-17.21 mm Standard Error 7.29	8.19 mm Standard Error 7.58

SECONDARY outcome

Timeframe: Baseline, Hour 156

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

1. : Mild

2. : Moderate

3. : Severe For subjects aged 2 to 6 years, this would not be evaluated. The negative value showed the degree of improvement.

Outcome measures

Measure	0.3% OPA-15406 Ointments n=15 Participants Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406	1% OPA-15406 Ointments n=17 Participants Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406	Placebo Ointments n=14 Participants Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos
Change From Baseline in Verbal Rating Scale(VRS) for Pruritus Score	-0.83 score on a scale Standard Error 0.18	-0.73 score on a scale Standard Error 0.19	0.30 score on a scale Standard Error 0.11

SECONDARY outcome

Timeframe: Baseline, Week 4

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.

Outcome measures

Measure	0.3% OPA-15406 Ointments n=23 Participants Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406	1% OPA-15406 Ointments n=24 Participants Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406	Placebo Ointments n=18 Participants Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos
Change From Baseline in Patient-Oriented Eczema Measure(POEM) Score	-4.33 score on a scale Standard Error 1.16	-4.37 score on a scale Standard Error 1.14	2.26 score on a scale Standard Error 1.24

SECONDARY outcome

Timeframe: Baseline, Week 8, 16, 24

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.

Outcome measures

Measure	0.3% OPA-15406 Ointments n=23 Participants Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406	1% OPA-15406 Ointments n=24 Participants Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406	Placebo Ointments n=18 Participants Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos
Change From Baseline in Percentage Affected Body Surface Area	-6.06 percentage of Affected Body Surface Area Standard Error 2.36	-8.21 percentage of Affected Body Surface Area Standard Error 2.32	1.78 percentage of Affected Body Surface Area Standard Error 2.53

SECONDARY outcome

Timeframe: Week 1

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.

Outcome measures

Measure	0.3% OPA-15406 Ointments n=18 Participants Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406	1% OPA-15406 Ointments n=21 Participants Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406	Placebo Ointments Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos
Mean (SD) OPA-15406 Plasma Trough Concentrations at week1	0.842 ng/mL Standard Deviation 0.577	2.90 ng/mL Standard Deviation 2.74	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	0.3% OPA-15406 Ointments n=20 Participants Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406	1% OPA-15406 Ointments n=22 Participants Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406	Placebo Ointments Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos
Mean (SD) OPA-15406 Plasma Trough Concentrations at week4	0.946 ng/mL Standard Deviation 1.16	2.21 ng/mL Standard Deviation 1.81	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	0.3% OPA-15406 Ointments n=18 Participants Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406	1% OPA-15406 Ointments n=21 Participants Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406	Placebo Ointments Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos
Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA at week1	0.196 ng/mL/mg Standard Deviation 0.201	0.210 ng/mL/mg Standard Deviation 0.174	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	0.3% OPA-15406 Ointments n=20 Participants Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406	1% OPA-15406 Ointments n=22 Participants Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406	Placebo Ointments Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos
Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA at week4	0.150 ng/mL/mg Standard Deviation 0.111	0.166 ng/mL/mg Standard Deviation 0.148	—

Adverse Events

0.3% OPA-15406 Ointments

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

1% OPA-15406 Ointments

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Placebo Ointments

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	0.3% OPA-15406 Ointments n=24 participants at risk Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406	1% OPA-15406 Ointments n=25 participants at risk Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406	Placebo Ointments n=24 participants at risk Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos
Infections and infestations Influenza	8.3% 2/24 • Treatment period	4.0% 1/25 • Treatment period	0.00% 0/24 • Treatment period
Infections and infestations Viral upper respiratory tract infection	4.2% 1/24 • Treatment period	0.00% 0/25 • Treatment period	8.3% 2/24 • Treatment period
Investigations Blood alkaline phosphatase increased	0.00% 0/24 • Treatment period	8.0% 2/25 • Treatment period	0.00% 0/24 • Treatment period
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	4.2% 1/24 • Treatment period	24.0% 6/25 • Treatment period	8.3% 2/24 • Treatment period
Skin and subcutaneous tissue disorders Dermatitis atopic	8.3% 2/24 • Treatment period	4.0% 1/25 • Treatment period	16.7% 4/24 • Treatment period

Additional Information

Director of Clinical Trials

Otsuka Pharmaceutical Co., LTD.

Phone: +81-3-6361-7366

Email: CL_OPCJ_RDA_Team@otsuka.jp

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place