Atopic Dermatitis
Conditions
Brief summary
This was a randomized, double blind, placebo controlled, parallel group study in approximately 90 subjects with moderate-severe AD Eczema Area and Severity Index (EASI) ≥12 and ≤ 48 (0-72 scale). Following a run-in subjects were randomized to receive either oral 30 mg ZPL-3893787 once daily (od) or placebo od for 8 weeks (56 days).
Interventions
DRUGZPL-3893787
ZPL-3893787
DRUGPlacebo
Matched Placebo
Sponsors
Ziarco Pharma Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Males and females aged 18-65 years inclusive with physician documented history or diagnosis of atopic dermatitis for at least 12 months prior to screening. Chronic AD should be diagnosed by the Eichenfield revised criteria of Hanifin and Rajka (Eichenfield, 2004) Eczema Area and Severity Index (EASI) of ≥12 and \<48. An Investigator's Global Assessment (IGA) score ≥ 3 at both Screening and Day 0. A mean pruritus score of ≥ 5 on a 0-10 scale over the 7 day Run In (Days -7 to -1) Atopic dermatitis affecting ≥10% BSA
Exclusion criteria
AD of such severity (EASI \>48) that the subject could not comply with the demands of the study and/or the subject is not a suitable candidate for a placebo-controlled study Have concurrent skin disease (e.g. acne) of such severity in the study area that it could interfere with the study evaluation or presence of skin comorbidities that may interfere with study assessments. Have an active skin infection or any other clinically apparent infections. Hypersensitivity to mometasone or to any other ingredients contained by the topical corticosteroid product used as rescue medication in the study. Have received phototherapy (e.g. UVA, UVB), or systemic therapy (e.g. immunosuppressants, cytostatics) known or suspected to have an effect on AD, within 4 weeks of the start of the Run In. Have received systemic corticosteroids (\[CS\] e.g. oral, intravenous, intraarticular, rectal) within 4 weeks of the start of the Run in. Subjects on a stable maintenance dose (over the preceding 3 months) of inhaled or intranasal CS may participate. Were treated with oral antihistamines or topical calcineurin inhibitors or topical steroids within 7 days of starting Run In; intranasal antihistamines for the treatment of allergic rhinitis are acceptable.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Numerical Rating Score (NRS) for Pruritus (Worst Itch) | Baseline to Week 8 | The participant used the Pruritus NRS to rate his or her worst itch in the previous 12 hours. This was assessed twice daily (in the morning soon after rising and the evening prior to retiring) and recorded in the eDiary. The scale ranges from 0 (no itching) to 10 (itching as bad as can be imagined). If only 1 measurement was collected on a particular day, that score was counted as the worst measurement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Eczema Area and Severity Index (EASI) Score | Baseline to Week 8 | The EASI is a validated tool used to measure the severity and extent of atopic eczema over 4 body regions (head and neck, upper limbs, trunk, and lower limbs). The intensity of a representative area of eczema and the approximate percentage affected by eczema are calculated for each region. A representative area of eczema is selected for each body region. The intensity of redness (erythema), thickness (induration, papulation, and edema), scratching (excoriation), and lichenification (lined skin) of eczema is assessed as: 0 - None 1. \- Mild 2. \- Moderate 3. \- Severe The total score incorporates the extent of body regions affected. Scores range from 0 to 72 with higher scores indicating more severe eczema. Total score is calculated by summing the EASI scores of 6 symptoms across 4 body regions |
Countries
Belgium, Germany, Poland, United Kingdom
Participant flow
Recruitment details
The first informed consent was on 18 May 2015. Subjects were randomly assigned 2:1 to receive either 30 mg ZPL-3893787 or matching placebo. The randomization was stratified by baseline worst daily pruritus NRS score (≤ 7.5 and \> 7.5) determined from the mean pruritus score (worst itch over 24 hours) collected during the 7-day Run-in Period.
Participants by arm
| Arm | Count |
|---|---|
| ZPL-3893787 30 mg ZPL-3893787 orally once daily for 8 weeks. | 65 |
| Placebo 1 capsule orally once daily for 8 weeks. | 33 |
| Total | 98 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Compliance problems | 1 | 0 |
| Overall Study | Consent withdrawn by subject | 4 | 1 |
| Overall Study | Lack of Efficacy | 0 | 7 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Other, unspecified | 1 | 0 |
| Overall Study | Physician Decision | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | ZPL-3893787 |
|---|---|---|---|
| Age, Continuous | 35.5 years STANDARD_DEVIATION 12.52 | 34.3 years STANDARD_DEVIATION 11.64 | 33.7 years STANDARD_DEVIATION 11.22 |
| Fitzpatrick Skin Type Type I | 4 participants | 6 participants | 2 participants |
| Fitzpatrick Skin Type Type II | 11 participants | 35 participants | 24 participants |
| Fitzpatrick Skin Type Type III | 14 participants | 46 participants | 32 participants |
| Fitzpatrick Skin Type Type IV | 2 participants | 5 participants | 3 participants |
| Fitzpatrick Skin Type Type V | 1 participants | 4 participants | 3 participants |
| Fitzpatrick Skin Type Type VI | 1 participants | 2 participants | 1 participants |
| Sex: Female, Male Female | 20 Participants | 56 Participants | 36 Participants |
| Sex: Female, Male Male | 13 Participants | 42 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 65 | 0 / 33 |
| other Total, other adverse events | 15 / 65 | 10 / 33 |
| serious Total, serious adverse events | 0 / 65 | 1 / 33 |
Outcome results
Primary
Change From Baseline in the Numerical Rating Score (NRS) for Pruritus (Worst Itch)
The participant used the Pruritus NRS to rate his or her worst itch in the previous 12 hours. This was assessed twice daily (in the morning soon after rising and the evening prior to retiring) and recorded in the eDiary. The scale ranges from 0 (no itching) to 10 (itching as bad as can be imagined). If only 1 measurement was collected on a particular day, that score was counted as the worst measurement.
Time frame: Baseline to Week 8
Population: Full Analysis Set (FAS): Included all randomized subjects who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ZPL-3893787 | Change From Baseline in the Numerical Rating Score (NRS) for Pruritus (Worst Itch) | Baseline summary | 7.3 score on a scale | Standard Deviation 1.139 |
| ZPL-3893787 | Change From Baseline in the Numerical Rating Score (NRS) for Pruritus (Worst Itch) | Week 8 summary | 4.27 score on a scale | Standard Deviation 2.253 |
| ZPL-3893787 | Change From Baseline in the Numerical Rating Score (NRS) for Pruritus (Worst Itch) | Change from Baseline | -3.03 score on a scale | Standard Deviation 2.186 |
| Placebo | Change From Baseline in the Numerical Rating Score (NRS) for Pruritus (Worst Itch) | Week 8 summary | 4.6 score on a scale | Standard Deviation 1.95 |
| Placebo | Change From Baseline in the Numerical Rating Score (NRS) for Pruritus (Worst Itch) | Baseline summary | 7.26 score on a scale | Standard Deviation 1.054 |
| Placebo | Change From Baseline in the Numerical Rating Score (NRS) for Pruritus (Worst Itch) | Change from Baseline | -2.66 score on a scale | Standard Deviation 2.057 |
Comparison: Change from baselinep-value: =0.24990% CI: [-1.21, 0.51]ANCOVA
Secondary
Change From Baseline in Eczema Area and Severity Index (EASI) Score
The EASI is a validated tool used to measure the severity and extent of atopic eczema over 4 body regions (head and neck, upper limbs, trunk, and lower limbs). The intensity of a representative area of eczema and the approximate percentage affected by eczema are calculated for each region. A representative area of eczema is selected for each body region. The intensity of redness (erythema), thickness (induration, papulation, and edema), scratching (excoriation), and lichenification (lined skin) of eczema is assessed as: 0 - None 1. \- Mild 2. \- Moderate 3. \- Severe The total score incorporates the extent of body regions affected. Scores range from 0 to 72 with higher scores indicating more severe eczema. Total score is calculated by summing the EASI scores of 6 symptoms across 4 body regions
Time frame: Baseline to Week 8
Population: FAS: All randomized subjects who received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ZPL-3893787 | Change From Baseline in Eczema Area and Severity Index (EASI) Score | Baseline | 21.39 score on a scale | Standard Deviation 7.889 |
| ZPL-3893787 | Change From Baseline in Eczema Area and Severity Index (EASI) Score | Week 8 summary | 10.67 score on a scale | Standard Deviation 9.541 |
| ZPL-3893787 | Change From Baseline in Eczema Area and Severity Index (EASI) Score | Week 8 change from baseline | -10.72 score on a scale | Standard Deviation 9.679 |
| Placebo | Change From Baseline in Eczema Area and Severity Index (EASI) Score | Baseline | 20.44 score on a scale | Standard Deviation 6.868 |
| Placebo | Change From Baseline in Eczema Area and Severity Index (EASI) Score | Week 8 summary | 15.06 score on a scale | Standard Deviation 11.159 |
| Placebo | Change From Baseline in Eczema Area and Severity Index (EASI) Score | Week 8 change from baseline | -5.38 score on a scale | Standard Deviation 9.922 |
Comparison: Change from baseline analysisp-value: =0.0190% CI: [-8.66, -1.46]ANCOVA