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

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

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.

Study Overview

• Status: Completed
• Conditions: Plaque Psoriasis
• Intervention / Treatment: Drug: (CP-6890,550) Tofacitinib; Drug: Placebo; Drug: (CP-690,550) Tofacitinib

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90045
      • Dermatology Research Associates
  • Florida
    • Tampa, Florida, United States, 33609
      • Olympian Clinical Research
  • Texas
    • Dallas, Texas, United States, 75246
      • Menter Dermatology Research Institute
    • Houston, Texas, United States, 77004
      • Center For Clinical Studies
    • Houston, Texas, United States, 77030
      • Center For Clinical Studies

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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). ‘Clear’ and “Almost clear’ 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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Panaccione R, Isaacs JD, Chen LA, Wang W, Marren A, Kwok K, Wang L, Chan G, Su C. Characterization of Creatine Kinase Levels in Tofacitinib-Treated Patients with Ulcerative Colitis: Results from Clinical Trials. Dig Dis Sci. 2021 Aug;66(8):2732-2743. doi: 10.1007/s10620-020-06560-4. Epub 2020 Aug 20. Erratum In: Dig Dis Sci. 2020 Oct 10;:
• Krueger J, Clark JD, Suarez-Farinas M, Fuentes-Duculan J, Cueto I, Wang CQ, Tan H, Wolk R, Rottinghaus ST, Whitley MZ, Valdez H, von Schack D, O'Neil SP, Reddy PS, Tatulych S; A3921147 Study Investigators. Tofacitinib attenuates pathologic immune pathways in patients with psoriasis: A randomized phase 2 study. J Allergy Clin Immunol. 2016 Apr;137(4):1079-1090. doi: 10.1016/j.jaci.2015.12.1318.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (ACTUAL): November 1, 2013
• Study Completion (ACTUAL): November 1, 2013

Study Registration Dates

• First Submitted: October 16, 2012
• First Submitted That Met QC Criteria: October 16, 2012
• First Posted (ESTIMATE): October 18, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): April 13, 2015
• Last Update Submitted That Met QC Criteria: March 30, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: tofacitinib; biopsy; plaque psoriasis; psoriasis vulgaris; Janus Kinase; randomized placebo controlled clinical trial
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tofacitinib
• Other Study ID Numbers: A3921147