Dermatitis, Atopic
Conditions
Keywords
Atopic Dermatitis, Atopic Eczema, Eczema, topical treatment, skin diseases, tofacitinib, CP-690, 550, Janus Kinase inhibitor
Brief summary
The study is being conducted to evaluate the efficacy, safety and tolerability of 2% tofacitinib ointment (20 mg/g) BID (twice daily) in subjects with mild to moderate atopic dermatitis compared to placebo (vehicle) BID for 4 weeks.
Interventions
DRUGTofacitinib ointment 20mg/g
Tofacitinib ointment 20mg/g twice daily (BID) for 4 weeks
Placebo ointment (vehicle) twice daily (BID) for 4 weeks
Sponsors
Pfizer
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 60 Years
Healthy volunteers
No
Inclusion criteria
* Have a clinical diagnosis of atopic dermatitis (also known as atopic eczema) for at least 6 months prior to Day 1 that has been clinically stable for at least 1 month prior to Day 1 and is confirmed to be atopic dermatitis according to the criteria of Hanifin and Rajka. * Have a PGA score of 2 (mild) or 3 (moderate) at Day 1. * Have atopic dermatitis on the head (including face, but excluding hair bearing scalp), neck, trunk (excluding groin and genitals), or limbs including palms and soles covering at least 2% of total body surface area (BSA) and up to and including 20% of total BSA at Day 1. At least 2% of the total BSA will need to be on the head (including face, but excluding hair bearing scalp), neck, trunk (excluding groin and genitals), or limbs (excluding palms and soles).
Exclusion criteria
* Evidence of certain skin conditions/infections at baseline * Currently have atopic dermatitis on groin, genitals, palm or soles * Have certain laboratory abnormalities at baseline * Females who are pregnant, breastfeeding, or are of childbearing potential not using highly effective contraception
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 4 | Baseline (pre-dose on Day 1) and Week 4 | The EASI quantifies the severity of a participant's atopic dermatitis based on both lesion severity and the percent of BSA affected. The EASI is a composite scoring by the atopic dermatitis clinical evaluator of the degree of erythema, induration/papulation, excoriation, and lichenification (each scored separately) for each of 4 body regions, with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of atopic dermatitis. What is reported is the percent change from baseline in EASI scores. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Achieving Physician's Global Assessment (PGA) Response of Clear or Almost Clear at Week 4 | Week 4 | The PGA score assesses the overall severity of atopic dermatitis. Scores range from 0 to 4 and correspond to a category (clear, almost clear, mild, moderate, and severe, respectively) based on morphological descriptors. |
| Proportion of Participants With Response of Clear or Almost Clear and Greater Than or Equal to (>=) 2 Grade/Point Improvement From Baseline at Week 4 | Baseline (pre-dose on Day 1) and Week 4 | The PGA score assesses the overall severity of atopic dermatitis. Scores range from 0 to 4 and correspond to a category (clear, almost clear, mild, moderate, and severe, respectively) based on morphological descriptors. |
| Percent Change From Baseline in Body Surface Area (BSA) Efficacy at Week 4 | Baseline (pre-dose on Day 1) and Week 4 | The percent BSA with atopic dermatitis in a body region was determined by the number of handprints of atopic dermatitis skin in that region: head and neck, upper limbs, trunk including axillae, lower limbs including buttocks. In the handprint method, the full palmar hand of the participant (i.e., the participant's fully extended palm, fingers and thumb together) represented approximately 1% of the total BSA. What is reported is the percent change from baseline in BSA affected. |
| Change From Baseline in the EASI Clinical Signs Severity Sum Score at Week 4 | Baseline (pre-dose on Day 1) and Week 4 | The EASI Clinical Signs Severity Sum Score was derived from the EASI. The Clinical Signs Severity Scores on the 4-point scale for dermatitis lesions were summed in each EASI body region. The sum of the Clinical Signs Severity Score in each EASI body region was then totaled across the 4 EASI body regions to provide an EASI Clinical Signs Severity Sum Score, which ranged from 0 to 48, with higher scores representing greater severity of atopic dermatitis. |
Countries
Canada
Participant flow
Recruitment details
Eligibility included male or female participants, 18 to 60 years of age (inclusive), who had a clinical diagnosis of atopic dermatitis for at least 6 months and clinically stable for \>=1 month.
Pre-assignment details
During the screening/washout period, participants' current therapies (topical, systemic, and phototherapy) for atopic dermatitis were discontinued and only non-medicated study emollient, sunscreen topical products, and specific shampoos (for atopic dermatitis on hair-bearing scalp) were permitted.
Participants by arm
| Arm | Count |
|---|---|
| Tofacitinib 20 mg/g BID Participants received tofacitinib (20 milligrams per gram \[mg/g, 2%\]) topical ointment to the treatment area twice a day (BID) for 4 weeks. | 35 |
| Vehicle BID Participants received placebo topical ointment vehicle to the treatment area BID for 4 weeks. | 34 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Tofacitinib 20 mg/g BID | Vehicle BID | Total |
|---|---|---|---|
| Age, Continuous | 32.4 years STANDARD_DEVIATION 9.8 | 30.4 years STANDARD_DEVIATION 10.4 | 31.4 years STANDARD_DEVIATION 10.1 |
| Sex: Female, Male Female | 19 Participants | 18 Participants | 37 Participants |
| Sex: Female, Male Male | 16 Participants | 16 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 35 | 19 / 34 |
| serious Total, serious adverse events | 0 / 35 | 0 / 34 |
Outcome results
Primary
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 4
The EASI quantifies the severity of a participant's atopic dermatitis based on both lesion severity and the percent of BSA affected. The EASI is a composite scoring by the atopic dermatitis clinical evaluator of the degree of erythema, induration/papulation, excoriation, and lichenification (each scored separately) for each of 4 body regions, with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of atopic dermatitis. What is reported is the percent change from baseline in EASI scores.
Time frame: Baseline (pre-dose on Day 1) and Week 4
Population: The full analysis set (FAS) included all participants who were randomized and received at least 1 dose of study drug. Missing data was not imputed. N=number of participants who were in FAS and had a baseline value and an observation at Week 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tofacitinib 20 mg/g BID | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 4 | -81.7 percent change | Standard Error 6.31 |
| Vehicle BID | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 4 | -29.9 percent change | Standard Error 6.46 |
p-value: <0.000180% CI: [-62.8, -40.8]Mixed Models Analysis
Secondary
Change From Baseline in the EASI Clinical Signs Severity Sum Score at Week 4
The EASI Clinical Signs Severity Sum Score was derived from the EASI. The Clinical Signs Severity Scores on the 4-point scale for dermatitis lesions were summed in each EASI body region. The sum of the Clinical Signs Severity Score in each EASI body region was then totaled across the 4 EASI body regions to provide an EASI Clinical Signs Severity Sum Score, which ranged from 0 to 48, with higher scores representing greater severity of atopic dermatitis.
Time frame: Baseline (pre-dose on Day 1) and Week 4
Population: The FAS included all participants who were randomized and received at least 1 dose of study drug. Missing data was not imputed. N=number of participants who were in FAS and had a baseline value and an observation at Week 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tofacitinib 20 mg/g BID | Change From Baseline in the EASI Clinical Signs Severity Sum Score at Week 4 | -11.4 units on a scale | Standard Deviation 5.3 |
| Vehicle BID | Change From Baseline in the EASI Clinical Signs Severity Sum Score at Week 4 | -4.1 units on a scale | Standard Deviation 4.5 |
Secondary
Percent Change From Baseline in Body Surface Area (BSA) Efficacy at Week 4
The percent BSA with atopic dermatitis in a body region was determined by the number of handprints of atopic dermatitis skin in that region: head and neck, upper limbs, trunk including axillae, lower limbs including buttocks. In the handprint method, the full palmar hand of the participant (i.e., the participant's fully extended palm, fingers and thumb together) represented approximately 1% of the total BSA. What is reported is the percent change from baseline in BSA affected.
Time frame: Baseline (pre-dose on Day 1) and Week 4
Population: The FAS included all participants who were randomized and received at least 1 dose of study drug. Missing data was not imputed. N=number of participants who were in FAS and had a baseline value and an observation at Week 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tofacitinib 20 mg/g BID | Percent Change From Baseline in Body Surface Area (BSA) Efficacy at Week 4 | -72.7 percent change | Standard Deviation 34.1 |
| Vehicle BID | Percent Change From Baseline in Body Surface Area (BSA) Efficacy at Week 4 | -30.2 percent change | Standard Deviation 39.4 |
Secondary
Proportion of Participants Achieving Physician's Global Assessment (PGA) Response of Clear or Almost Clear at Week 4
The PGA score assesses the overall severity of atopic dermatitis. Scores range from 0 to 4 and correspond to a category (clear, almost clear, mild, moderate, and severe, respectively) based on morphological descriptors.
Time frame: Week 4
Population: The FAS included all participants who were randomized and received at least 1 dose of study drug. Participants who were in FAS and had a baseline PGA score of 2 or 3 were included in the analysis. Participants with missing data at Week 4 were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tofacitinib 20 mg/g BID | Proportion of Participants Achieving Physician's Global Assessment (PGA) Response of Clear or Almost Clear at Week 4 | 71.4 percentage of participants |
| Vehicle BID | Proportion of Participants Achieving Physician's Global Assessment (PGA) Response of Clear or Almost Clear at Week 4 | 20.6 percentage of participants |
Secondary
Proportion of Participants With Response of Clear or Almost Clear and Greater Than or Equal to (>=) 2 Grade/Point Improvement From Baseline at Week 4
The PGA score assesses the overall severity of atopic dermatitis. Scores range from 0 to 4 and correspond to a category (clear, almost clear, mild, moderate, and severe, respectively) based on morphological descriptors.
Time frame: Baseline (pre-dose on Day 1) and Week 4
Population: The FAS included all participants who were randomized and received at least 1 dose of study drug. Participants who were in FAS and had a baseline PGA score of 2 or 3 were included in the analysis. Participants with missing data at Week 4 were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tofacitinib 20 mg/g BID | Proportion of Participants With Response of Clear or Almost Clear and Greater Than or Equal to (>=) 2 Grade/Point Improvement From Baseline at Week 4 | 65.7 percentage of participants |
| Vehicle BID | Proportion of Participants With Response of Clear or Almost Clear and Greater Than or Equal to (>=) 2 Grade/Point Improvement From Baseline at Week 4 | 11.8 percentage of participants |