Study Of The Mechanism Of Action Of CP-690,550 In The Skin Of Subjects With Moderate To Severe Chronic Plaque Psoriasis

Study Overview
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Brief Summary
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There are cells in the skin and blood of humans with chronic moderate to severe plaque psoriasis with specific activities that may determine the effectiveness of treatment. These activities may be described by obtaining samples of skin and blood and analyzing them using a variety of tests.

Detailed Description
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The final subject in Cohort 1 completed the study on 19-Nov-2013 (LSLV date). Because the study analyses were novel and exploratory, they required extensive analyses by study team and external experts. As a result of this analysis it was determined on 21-July-2014 that the data from Cohort 1 were sufficiently definitive and that enrollment of Cohort 2 would not be justified. Since this decision resulted in the LSLV for Cohort 1 becoming the LSLV for the study, the full data analysis and reporting is not projected to be complete within 12 Months of LSLV. The final analysis and final reporting is planned to be completed on 18-Feb-2015. Results for this data are anticipated to be released in April 2015.

Official Title
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An Exploratory Phase 2a, Randomized, Double-blind, Placebo-controlled, Multicenter Study To Assess Mechanism Of Action (Moa) Of Cp-690,550 In The Skin When Administered Orally At 10 Mg Twice Daily (Bid) For 12 Weeks In Subjects With Moderate To Severe Chronic Plaque Psoriasis

Conditions
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Plaque Psoriasis

Intervention / Treatment
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* Drug: (CP-6890,550) Tofacitinib
* Drug: Placebo
* Drug: (CP-690,550) Tofacitinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults over 18 years of age with a diagnosis of chronic moderate to severe plaque psoriasis for at least 12 months; in generally good health; on stable dose of non-prohibited medications; able to stop current psoriasis therapy (systemic or topical) for several weeks prior to and during study participation. Exclusion Criteria: Serious underlying disease including viral disorders such as hepatitis or HIV or skin condition that would interfere with skin biopsies or evaluation of psoriasis; conditions that could interfere with drug absorption after oral administration; history of malignancy or auto-immune disease. Use of oral or injected corticosteroids (steroids).

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br> | Drug: (CP-6890,550) Tofacitinib<br>* 2 x 5 mg oral capsules taken twice daily (every 12 hours) for 12 consecutive weeks<br>Drug: Placebo<br>* 2 matching oral capsules taken twice daily (every 12 hours) for 12 consecutive weeks<br>|
| Experimental: Cohort 2<br> | Drug: (CP-690,550) Tofacitinib<br>* 2 x 5 mg oral capsules taken twice daily (every 12 hours) for 12 weeks<br>Drug: Placebo<br>* 2 matching oral capsules taken twice daily (every 12 hours) for 12 consecutive weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving a 75% Reduction in the Psoriasis Area and Severity Index (PASI75) at Week 12 | Combined assessment of lesion severity and area affected into single score; range equals (=) 0 (no disease) to 72 (maximal disease). Body divided into 4 sections=head, upper/lower limbs, trunk; each area scored by itself and scores combined for final PASI. For each section percent area of skin involved was estimated: 0 (0%) to 6 (90-100%) and severity estimated by clinical signs of erythema, induration, scaling; ranged 0-4: 0=none, 1=slight, 2=moderate, 3=marked, 4=very marked. Final PASI=sum of severity parameters for each section*area score*weighing factor (head=0.1, upper limbs=0.2, trunk=0.3, lower limbs=0.4) summed over all sections. | Week 12 | 
| Percentage of Participants Achieving a Physician's Global Assessment (PGA) Response of Clear or Almost Clear at Week 12 | PGA psoriasis is scored on a 5-point scale, reflecting a global consideration of the erythema, induration and scaling across all psoriatic lesions. PGA of Psoriasis scale ranges from 0 (no psoriasis) to 4 (severe disease). â€˜Clearâ€™ and â€œAlmost clearâ€™ includes all participants who were scored as a 0 or 1. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psoriasis Area and Severity Index (PASI) Score by Visit | Combined assessment of lesion severity and area affected into single score. Body was divided into 4 sections: head, arms, trunk, legs. For each section, percent area of skin involved was estimated: 0=0% to 6=90â€100%. Severity was estimated by clinical signs: erythema, induration, desquamation; scale: 0= none to 4= maximum. Final PASI = sum of severity parameters for each section*area score*weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4) summed over all sections; total possible score range: 0= no disease to 72= maximal disease. | Baseline and Weeks 1, 2, 4, and 12 | 
| Change From Baseline in PASI by Visit | Combined assessment of lesion severity and area affected into single score. Body was divided into 4 sections: head, arms, trunk, legs. For each section, percent area of skin involved was estimated: 0=0% to 6=90â€100%. Severity was estimated by clinical signs: erythema, induration, desquamation; scale: 0= none to 4= maximum. Final PASI = sum of severity parameters for each section*area score*weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4) summed over all sections; total possible score range: 0= no disease to 72= maximal disease. | Weeks 1, 2, 4 and 12 | 
| Percent Change From Baseline in PASI by Visit | Combined assessment of lesion severity and area affected into single score. Body was divided into 4 sections: head, arms, trunk, legs. For each section, percent area of skin involved was estimated: 0= 0% to 6= 90â€100%. Severity was estimated by clinical signs: erythema, induration, desquamation; scale: 0= none to 4= maximum. Final PASI = sum of severity parameters for each section*area score*weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4) summed over all sections; total possible score range: 0= no disease to 72= maximal disease. | Weeks 1, 2, 4, and 12 | 
| Percentage of Participants Achieving a PASI75 Response at Weeks 1, 2, and 4 | Combined assessment of lesion severity and area affected into single score; range=0 (no disease) to 72 (maximal disease). Body divided into 4 sections=head, upper/lower limbs, trunk; each area scored by itself and scores combined for final PASI. For each section percent area of skin involved was estimated: 0 (0%) to 6 (90-100%) and severity estimated by clinical signs of erythema, induration, scaling; ranged 0-4: 0=none, 1=slight, 2=moderate, 3=marked, 4=very marked. Final PASI=sum of severity parameters for each section*area score*weighing factor (head=0.1, upper limbs=0.2, trunk=0.3, lower limbs=0.4) summed over all sections. | Weeks 1, 2, and 4 | 
| Change From Baseline in PGA Score by Visit | PGA psoriasis is scored on a 5-point scale, reflecting a global consideration of the erythema, induration, and scaling across all psoriatic lesions. PGA of Psoriasis scale ranges from 0 (no psoriasis) to 4 (severe disease). The severity scores of 3 components (erythema, induration, and scaling) are averaged and rounded to the nearest whole number to determine the PGA score. | Weeks 1, 2, 4, and 12 | 
| Percentage of Participants in Each PGA Category at Various Timepoints by Baseline Category |  | Baseline and Weeks 1, 2, 4, and 12 | 
| Percentage of Participants by PGA Response Category and Timepoint | PGA psoriasis is scored on a 5-point scale, reflecting a global consideration of the erythema, induration and scaling across all psoriatic lesions. PGA of Psoriasis scale ranges from 0 (no psoriasis) to 4 (severe disease). Response category scores: 0=clear; 1=almost clear; 2=mild; 3=moderate; and 4=severe. The severity scores of 3 components (erythema, induration, and scaling) are averaged and rounded to the nearest whole number to determine the PGA score. | Baseline and Weeks 1, 2, 4, and 12 | 
| Body Surface Area (BSA) | Assessment of BSA with psoriasis was performed separately for 4 body regions: head and neck, upper limbs, trunk (including axillae and groin), and lower limbs (including buttocks). The percent surface area with psoriasis was estimated by means of the handprint method, where the full palmar hand of the participant (ie, the participant's fully extended palm, fingers and thumb together) represents approximately 1% of the total BSA. The number of handprints of psoriatic skin in a body region can be used to determine the extent (%) to which a body regions is involved with psoriasis. In each body region, the percent body region surface area with psoriasis is multiplied by the Body Region Weighting (head and neck=10%, upper limbs=5%, trunk [including axillae and groin]=3.33% and lower limbs [including buttocks]=2.5%). BSA (%)=0.1Sh + 0.2Sh+0.3St+0.4Sl, where S=body region suface area with psoriasis: h=head; u=upper limbs; t=trunk; l=lower limbs. | Baseline and Weeks 1, 2, 4, and 12 | 
| Change From Baseline in BSA | Assessment of BSA with psoriasis was performed separately for 4 body regions: head and neck, upper limbs, trunk (including axillae and groin), and lower limbs (including buttocks). The percent surface area with psoriasis was estimated by means of the handprint method, where the full palmar hand of the participant (ie, the participant's fully extended palm, fingers and thumb together) represents approximately 1% of the total BSA. The number of handprints of psoriatic skin in a body region can be used to determine the extent (%) to which a body regions is involved with psoriasis. In each body region, the percent body region surface area with psoriasis is multiplied by the Body Region Weighting (head and neck=10%, upper limbs=5%, trunk [including axillae and groin]=3.33% and lower limbs [including buttocks]=2.5%). BSA (%)=0.1Sh + 0.2Sh+0.3St+0.4Sl, where S=body region suface area with psoriasis: h=head; u=upper limbs; t=trunk; l=lower limbs. | Weeks 1, 2, 4, and 12 | 
| Percent Change From Baseline in BSA | Assessment of BSA with psoriasis was performed separately for 4 body regions: head and neck, upper limbs, trunk (including axillae and groin), and lower limbs (including buttocks). The percent surface area with psoriasis was estimated by means of the handprint method, where the full palmar hand of the participant (ie, the participant's fully extended palm, fingers and thumb together) represents approximately 1% of the total BSA. The number of handprints of psoriatic skin in a body region can be used to determine the extent (%) to which a body regions is involved with psoriasis. In each body region, the percent body region surface area with psoriasis is multiplied by the Body Region Weighting (head and neck=10%, upper limbs=5%, trunk [including axillae and groin]=3.33% and lower limbs [including buttocks]=2.5%). BSA (%)=0.1Sh + 0.2Sh+0.3St+0.4Sl, where S=body region suface area with psoriasis: h=head; u=upper limbs; t=trunk; l=lower limbs. | Weeks 1, 2, 4, and 12 | 
| Itch Severity Item (ISI) Score by Visit | The severity of itch (pruritus) due to psoriasis was assessed using the ISI, a single-item, horizontal numeric rating scale. Participants were asked to rate your worst itching due to psoriasis over the past 24 hours on a numeric rating scale anchored by the terms No itching (0) and Worst possible itching (10) at the ends. the baseline is defined as the average of all available diary entries before Baseline/Day 1 and the in-clinic measurement on Baseline/day 1. Week 1 is the mean of daily values of study days 2 to 8 and Week 2 is the mean of daily values of study days 9 to 15. | Baseline and Weeks 1, 2, 4, and 12 | 
| Change From Baseline in ISI by Visit | ISI, a single-item, horizontal numeric rating scale. Participants were asked to rate your worst itching due to psoriasis over the past 24 hours on a numeric rating scale anchored by the terms No itching (0) and Worst possible itching (10) at the ends. The baseline is defined as the average of all available diary entries before Baseline/Day 1 and the in-clinic measurement on Baseline/Day 1. Week 1 is the mean of daily values of study days 2 to 8 and Week 2 is the mean of daily values of study days 9 to 15. A negative value indicates an improvement. | Weeks 1, 2, 4 and 12 | 
| Target Plaque Severity Score (TPSS) by Visit | Target lesions were selected at baseline and followed for the duration of the study. Each target lesion was scored by the investigator on severity of erythema, induration, and scaling according to a 5-point (0 to 4) severity scale with a maximum sum score for a plaque of 12. The TPSS was calculated as the sum of the scores for erythema, induration, and scaling; the score can vary in increments of 1 unit from 0 to 12. | Baseline and Weeks 1, 2, 4, and 12 | 
| Percent Change From Baseline in TPSS by Visit | Target lesions were selected at baseline and followed for the duration of the study. Each target lesion was scored by the investigator on severity of erythema, induration, and scaling according to a 5-point (0 to 4) severity scale with a maximum sum score for a plaque of 12. The TPSS was calculated as the sum of the scores for erythema, induration, and scaling; the score can vary in increments of 1 unit from 0 to 12. A negative value indicated improvment. | Weeks 1, 2, 4, and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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plaque psoriasis, tofacitinib, biopsy, Janus Kinase, randomized placebo controlled clinical trial, psoriasis vulgaris