Tofacitinib Ointment For Chronic Plaque Psoriasis

A Phase 2b, Multi-site, Randomized, Double-blind, Vehicle-controlled, Parallel-group Study Of The Efficacy, Safety, Local Tolerability And Pharmacokinetics Of 2 Dose Strengths And 2 Regimens Of Tofacitinib Ointment In Subjects With Chronic Plaque Psoriasis.

The study is beng done to test if tofacitinib ointment is safe and effective for people with plaque psoriasis. Two dose strengths of tofacitinib ointment (20 mg/g and 10 mg/g) applied once or twice daily are being tested. The safety and effectiveness of tofacitinib ointment used for 12 weeks will be compared to the safety and effectiveness of placebo ointment (vehicle) used for 12 weeks.

Study Overview

• Status: Completed
• Conditions: Psoriasis; Psoriasis Vulgaris
• Intervention / Treatment: Drug: tofacitinib ointment 20 mg/g; Drug: tofacitinib ointment 20 mg/g; Drug: tofacitinib ointment 10 mg/g; Drug: tofacitinib ointment 10 mg/g; Drug: placebo ointment (vehicle); Drug: placebo ointment (vehicle)

• Study Type: Interventional
• Enrollment (Actual): 476
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T5K 1X3
      • Stratica Medical
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3C 1R4
      • Dermadvances Research
  • Ontario
    • Ajax, Ontario, Canada, L1S 7K8
      • CCA Medical Research Corporation
    • Barrie, Ontario, Canada, L4M 6L2
      • Ultranova Skincare
    • Hamilton, Ontario, Canada, L8N 1V6
      • Dermatrials Research
    • London, Ontario, Canada, N6A 3H7
      • The Guenther Dermatology Research Centre
    • Markham, Ontario, Canada, L3P1X2
      • Lynderm Research Inc
    • Peterborough, Ontario, Canada, K9J 1Z2
      • Skin Centre for Dermatology
    • Waterloo, Ontario, Canada, N2J 1C4
      • K. Papp Clinical Research Inc.
    • Windsor, Ontario, Canada, N8W 1E6
      • XLR8 Medical Research
  • Quebec
    • Montreal, Quebec, Canada, H2K 4L5
      • Innovaderm Research Inc
    • Montreal, Quebec, Canada, H3Z 2S6
      • Siena Medical Research
• Denmark
  • Aarhus C, Denmark, 8000
    • Dermatologisk Afdeling S
  • Herning, Denmark, 7400
    • Hudklinikken Herning
• Poland
  • Bialystok, Poland, 15-351
    • ZDROWIE OSTEO-MEDIC s.c. Lidia i Artur Racewicz, Agnieszka i Jerzy Supronik
  • Bialystok, Poland, 15-879
    • NZOZ Centrum Osteoporozy i Chorob Kostno-Stawowych J. Badurski Spolka Jawna
  • Gdansk, Poland, 80-152
    • Pomorskie Centrum Traumatologii im.Mikolaja Kopernika w Gdansku Oddzial Dermatologii
  • Krakow, Poland, 31-501
    • Krakowskie Centrum Medyczne Sp. z o.o.
  • Lublin, Poland, 20-080
    • Maxxmed Centrum Zdrowia i Urody
  • Poznan, Poland, 61-841
    • Gabinet Lekarski RTG USG Dr n. med. Pawel Skrzywanek; Pracownia Radiologiczna
  • Warszawa, Poland, 01-817
    • High-Med. Przychodnia Specjalistyczna
  • Warszawa 44, Poland, 04-141
    • Wojskowy Instytut Medyczny
  • Wroclaw, Poland, 51-318
    • NZOZ multiMedica
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-758
      • Klinika Ambroziak ESTEDERM Sp. z o.o.SKA
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland, 60-539
      • NZOZ Solumed
• United States
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Burke Pharmaceutical Research
  • California
    • Bakersfield, California, United States, 93304
      • Bakersfield Dermatology and Skin Cancer Medical Center
    • Irvine, California, United States, 92697
      • UC Irvine Dermatology Research
    • Los Angeles, California, United States, 90045
      • Dermatology Research Associates
  • Florida
    • Orange Park, Florida, United States, 32073
      • Park Avenue Dermatology, PA
    • Tampa, Florida, United States, 33609
      • Olympian Clinical Research
  • Georgia
    • Alpharetta, Georgia, United States, 30022
      • Atlanta Dermatology, Vein & Research Center
    • Atlanta, Georgia, United States, 30342
      • Advanced Medical Research, Inc
    • Newnan, Georgia, United States, 30263
      • MedaPhase Inc.
  • Illinois
    • West Dundee, Illinois, United States, 60118
      • Dundee Dermatology
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital - Clinical Unit for Research Trials in Skin (CURTIS)
  • Michigan
    • Clinton Township, Michigan, United States, 48038
      • Michigan Center for Skin Care Research
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • Dermatology Consulting Services
    • Winston-Salem, North Carolina, United States, 27104
      • Wake Forest University Health Sciences
  • Ohio
    • Cincinnati, Ohio, United States, 45249
      • Radiant Research, Inc.
  • Oregon
    • Portland, Oregon, United States, 97210
      • Oregon Dermatology and Research Center
    • Portland, Oregon, United States, 97223
      • Oregon Medical Research Center, Pc
  • Rhode Island
    • Johnston, Rhode Island, United States, 02919
      • Clinical Partners, LLC
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Greer, South Carolina, United States, 29650
      • Radiant Research, Inc.
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Health Concepts
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Dermatology Research Associates
  • Texas
    • Arlington, Texas, United States, 76011
      • Arlington Research Center Inc.
    • Dallas, Texas, United States, 75246
      • Menter Dermatology Research Institute
    • Dallas, Texas, United States, 75230
      • Dermatology Treatment and Research Center
    • Houston, Texas, United States, 77056
      • Suzanne Bruce and Associates, PA
    • San Antonio, Texas, United States, 78229
      • Progressive Clinical Research
    • San Antonio, Texas, United States, 78229
      • Lee Medical Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have mild, moderate or severe plaque psoriasis (psoriasis vulgaris) for at least 6 months prior to Baseline
• At Baseline, have plaque psoriasis covering 2% to 20% of total body surface area (BSA) on the trunk and limbs (excluding palms, soles, and nails)
• If received certain treatments, should be off treatment for a minimum period of time (washout)

Exclusion Criteria:

• Currently have non-plaque forms of psoriasis or drug-induced psoriasis
• Require treatment with or cannot stop medication(s) prohibited during the study
• Have certain laboratory abnormalities at Baseline
• Current or history of certain infections
• Females who are pregnant, breastfeeding, or are of childbearing potential not using highly effective contraception

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group A	Drug: tofacitinib ointment 20 mg/g; tofacitinib ointment 20 mg/g BID (twice daily) for 12 weeks; Drug: tofacitinib ointment 20 mg/g; tofacitinib ointment 20 mg/g QD (once daily) for 12 weeks
Experimental: Treatment Group B	Drug: tofacitinib ointment 10 mg/g; tofacitinib ointment 10 mg/g BID (twice daily) for 12 weeks; Drug: tofacitinib ointment 10 mg/g; tofacitinib ointment 10 mg/g QD (once daily) for 12 weeks
Placebo Comparator: Treatment Group C	Drug: placebo ointment (vehicle); placebo ointment (vehicle) BID (twice daily) for 12 weeks; Drug: placebo ointment (vehicle); placebo ointment (vehicle) QD (once daily) for 12 weeks
Experimental: Treatment Group D	Drug: tofacitinib ointment 20 mg/g; tofacitinib ointment 20 mg/g BID (twice daily) for 12 weeks; Drug: tofacitinib ointment 20 mg/g; tofacitinib ointment 20 mg/g QD (once daily) for 12 weeks
Experimental: Treatment Group E	Drug: tofacitinib ointment 10 mg/g; tofacitinib ointment 10 mg/g BID (twice daily) for 12 weeks; Drug: tofacitinib ointment 10 mg/g; tofacitinib ointment 10 mg/g QD (once daily) for 12 weeks
Placebo Comparator: Treatment Group F	Drug: placebo ointment (vehicle); placebo ointment (vehicle) BID (twice daily) for 12 weeks; Drug: placebo ointment (vehicle); placebo ointment (vehicle) QD (once daily) for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving a PGA-C Response of Clear (0) or Almost Clear (1) and Greater Than or Equal to (≥) 2 Grade/Point Improvement From Baseline at Week 12	Clinical signs of plaque psoriasis (erythema [E], induration [I], and scaling [S]) were scored separately according to a 5-point severity scale (0 to 4) to provide PGA subscores, which described the overall severity of each clinical sign. The PGA-C was a static assessment; i.e., without regard to a previous assessment. The PGA subscores are then summed and averaged after which the total average was rounded to the nearest whole number to determine the PGA-C score and category. A higher score indicated a higher level of severity. 0 is equal to (=) cleared except for any residual discoloration and 1=almost clear, majority of lesions had individual scores for E+I+S that when summed, averaged, and rounded equaled 1.	Baseline, Week 12
Percentage of Participants Achieving a PGA-C Response of Clear (0) or Almost Clear (1) and ≥2 Grade/Point Improvement From Baseline at Week 8	Clinical signs of plaque psoriasis (E, I, and S) were scored separately according to a 5-point severity scale (0 to 4) to provide PGA subscores, which described the overall severity of each clinical sign. The PGA-C was a static assessment; i.e., without regard to a previous assessment. The PGA subscores are then summed and averaged after which the total average was rounded to the nearest whole number to determine the PGA-C score and category. A higher score indicated a higher level of severity. 0 is equal to (=) cleared except for any residual discoloration and 1=almost clear, majority of lesions had individual scores for E+I+S that when summed, averaged, and rounded equaled 1.	Baseline, Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving a PGA-C Response of Clear (0) or Almost Clear (1) at Week 12	Clinical signs of plaque psoriasis (E, I, and S) were scored separately according to a 5-point severity scale (0 to 4) to provide PGA subscores, which described the overall severity of each clinical sign. The PGA-C was a static assessment; i.e., without regard to a previous assessment. The PGA subscores are then summed and averaged after which the total average was rounded to the nearest whole number to determine the PGA-C score and category. A higher score indicated a higher level of severity. 0 is equal to (=) cleared except for any residual discoloration and 1=almost clear, majority of lesions had individual scores for E+I+S that when summed, averaged, and rounded equaled 1.	Week 12
Percentage of Participants Achieving a PGA-C Response of Clear (0) or Almost Clear (1) at Week 8	Clinical signs of plaque psoriasis (E, I, and S) were scored separately according to a 5-point severity scale (0 to 4) to provide PGA subscores, which described the overall severity of each clinical sign. The PGA-C was a static assessment; i.e., without regard to a previous assessment. The PGA subscores are then summed and averaged after which the total average was rounded to the nearest whole number to determine the PGA-C score and category. A higher score indicated a higher level of severity. 0 is equal to (=) cleared except for any residual discoloration and 1=almost clear, majority of lesions had individual scores for E+I+S that when summed, averaged, and rounded equaled 1.	Week 8
Percentage of Participants Achieving a Gestalt Physician's Global Assessment (PGA-G) Response of Clear (0) or Almost Clear (1) and ≥2 Grade/Point Improvement From Baseline at Week 12	Clinical signs of plaque psoriasis (E, I and S) were scored separately according to a 5-point severity scale (0 to 4) to provide PGA subscores, which described the overall severity of each clinical sign. After scoring each of the PGA subscores, a clinical evaluator of psoriasis performed an assessment of the overall severity of psoriasis and assigned a PGA-G score and category. 0=Clear, except for any residual discoloration (post-inflammatory hyperpigmentation and/or hypopigmentation) and 1=almost clear, the psoriasis is not entirely cleared and remaining plaques are light pink (not including post inflammatory hyperpigmentation), and/or have barely palpable elevation and/or have occasional fine scale. The PGA-G was a static assessment; i.e., without regard to a previous assessment.	Baseline, Week 12
Percentage of Participants Achieving a PGA-G Response of Clear (0) or Almost Clear (1) and ≥2 Grade/Point Improvement From Baseline at Week 8	Clinical signs of plaque psoriasis (E, I and S) were scored separately according to a 5-point severity scale (0 to 4) to provide PGA subscores, which described the overall severity of each clinical sign. After scoring each of the PGA subscores, a clinical evaluator of psoriasis performed an assessment of the overall severity of psoriasis and assigned a PGA-G score and category. 0=Clear, except for any residual discoloration (post-inflammatory hyperpigmentation and/or hypopigmentation) and 1=almost clear, the psoriasis is not entirely cleared and remaining plaques are light pink (not including post inflammatory hyperpigmentation), and/or have barely palpable elevation and/or have occasional fine scale. The PGA-G was a static assessment; i.e., without regard to a previous assessment.	Baseline, Week 8
Percent Change From Baseline to Week 12 in Psoriasis Area and Severity Index (PASI)	Combined assessment of lesion severity and area affected into single score. Body was divided into 4 regions: head, arms, trunk, legs. For each region, percent (%) area of skin involved was estimated: 0=0% to 6=90-100%. Severity was estimated by clinical signs: erythema, induration, scaling; scale: 0=none to 4=maximum. Final PASI = sum of severity parameters for each region*area score*weight of region (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4); total possible score range: 0=no disease to 72=maximal disease. The maximum PASI score was <72 since the PASI assessment excluded scalp, palms, finger nails, soles, and toe nails.	Baseline, Week 12
Percent Change From Baseline to Week 8 in PASI	Combined assessment of lesion severity and area affected into single score. Body was divided into 4 regions: head, arms, trunk, legs. For each region, percent area of skin involved was estimated: 0=0% to 6=90-100%. Severity was estimated by clinical signs: erythema, induration, scaling; scale: 0=none to 4=maximum. Final PASI = sum of severity parameters for each region*area score*weight of region (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4); total possible score range: 0=no disease to 72=maximal disease. The maximum PASI score was <72 since the PASI assessment excluded scalp, palms, finger nails, soles, and toe nails.	Baseline, Week 8
Percentage of Participants Achieving at Least a 75% Reduction in PASI Response (PASI75), Relative to Baseline at Week 12	Combined assessment of lesion severity and area affected into single score. Body was divided into 4 regions: head, arms, trunk, legs. For each region, percent area of skin involved was estimated: 0=0% to 6=90-100%. Severity was estimated by clinical signs: erythema, induration, scaling; scale: 0=none to 4=maximum. Final PASI = sum of severity parameters for each region*area score*weight of region (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4); total possible score range: 0=no disease to 72=maximal disease. The maximum PASI score was <72 since the PASI assessment excluded scalp, palms, finger nails, soles, and toe nails.	Baseline, Week 12
Percentage of Participants Achieving PASI75, Relative to Baseline at Week 8	Combined assessment of lesion severity and area affected into single score. Body was divided into 4 regions: head, arms, trunk, legs. For each region, percent area of skin involved was estimated: 0=0% to 6=90-100%. Severity was estimated by clinical signs: erythema, induration, scaling; scale: 0=none to 4=maximum. Final PASI = sum of severity parameters for each region*area score*weight of region (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4); total possible score range: 0=no disease to 72=maximal disease. The maximum PASI score was <72 since the PASI assessment excluded scalp, palms, finger nails, soles, and toe nails.	Baseline, Week 8
Percent Change From Baseline to Week 12 in Body Surface Area (BSA) Affected With Psoriasis	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 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. BSA (%)=the sum of the BSAs of the 4 body regions. BSA assessment excluded head and neck, palms, finger nails, soles and toe nails.	Baseline, Week 12
Percent Change From Baseline to Week 8 in BSA Affected With Psoriasis	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 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. BSA (%)=the sum of the BSAs of the 4 body regions. BSA assessment excluded head and neck, palms, finger nails, soles and toe nails.	Baseline, Week 8
Change From Baseline to Week 12 in Clinic-Based Itch Severity Item (ISI) Scores	The severity of itch (pruritus) due to psoriasis was assessed using the ISI. Participants were asked to assess their "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. Participants completed the ISI assessments at the clinic (i.e., clinic-based).	Baseline, Week 12
Change From Baseline to Week 8 in Clinic-Based ISI Scores	The severity of itch (pruritus) due to psoriasis was assessed using the ISI. Participants were asked to assess their "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. Participants completed the ISI assessments at the clinic (i.e., clinic-based).	Baseline, Week 8
Change From Baseline to Week 12 in the Dermatology Life Quality Index (DLQI) Total Score	DLQI is the dermatology-specific quality of life measure used for psoriatic population. The 10-item questionnaire assesses participant health-related quality of life (daily activities, personal relationships, symptoms and feelings, leisure, work and school, and treatment). The DLQI questions are rated by the participant as 0 (not at all/not relevant) to 3 (very much) with a total score range of 0 (best) to 30 (worst); higher scores indicate poor quality of life.	Baseline, Week 12
Change From Baseline to Week 8 in the DLQI Total Score	DLQI is the dermatology-specific quality of life measure used for psoriatic population. The 10-item questionnaire assesses participant health-related quality of life (daily activities, personal relationships, symptoms and feelings, leisure, work and school, and treatment). The DLQI questions are rated by the participant as 0 (not at all/not relevant) to 3 (very much) with a total score range of 0 (best) to 30 (worst); higher scores indicate poor quality of life.	Baseline, Week 8
Percentage of Participants Achieving a Patient's Global Assessment (PtGA) Response of Clear (0) or Almost Clear (1) and ≥2 Grade/Point Improvement From Baseline at Week 12 for Participants With a PtGA Score ≥2 at Baseline	The PtGA asks the participant to evaluate the overall cutaneous disease at that point in time on a single item, 5-point scale (0=clear; 1=almost clear; 2=mild; 3=moderate; 4=severe).	Baseline, Week 12
Percentage of Participants Achieving a PtGA Response of Clear (0) or Almost Clear (1) and ≥2 Grade/Point Improvement From Baseline at Week 8 for Participants With a PtGA Score ≥2 at Baseline	The PtGA asks the participant to evaluate the overall cutaneous disease at that point in time on a single item, 5-point scale (0=clear; 1=almost clear; 2=mild; 3=moderate; 4=severe).	Baseline, Week 8

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Papp KA, Bissonnette R, Gooderham M, Feldman SR, Iversen L, Soung J, Draelos Z, Mamolo C, Purohit V, Wang C, Ports WC. Treatment of plaque psoriasis with an ointment formulation of the Janus kinase inhibitor, tofacitinib: a Phase 2b randomized clinical trial. BMC Dermatol. 2016 Oct 3;16(1):15. doi: 10.1186/s12895-016-0051-4.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: March 28, 2013
• First Submitted That Met QC Criteria: April 10, 2013
• First Posted (Estimate): April 15, 2013

Study Record Updates

• Last Update Posted (Estimate): November 25, 2015
• Last Update Submitted That Met QC Criteria: October 26, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: topical treatment; skin diseases; psoriasis; Xeljanz; severe; moderate; Tofacitinib; CP-690550; itch; plaque psoriasis; nail psoriasis; vulgaris; papulosquamous
• 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: A3921082; 2012-005645-20 (EudraCT Number)