Tofacitinib Ointment For Chronic Plaque Psoriasis

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Psoriasis Vulgaris, Psoriasis

Intervention / Treatment
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* Drug: tofacitinib ointment 20 mg/g
* Drug: tofacitinib ointment 10 mg/g
* Drug: placebo ointment (vehicle)
* Drug: tofacitinib ointment 20 mg/g
* Drug: tofacitinib ointment 10 mg/g
* Drug: placebo ointment (vehicle)


Participation Criteria
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Eligibility Criteria
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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

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: Quadruple


Arms and Interventions

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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plaque psoriasis, vulgaris, topical treatment, skin diseases, papulosquamous, Tofacitinib, CP-690550, Xeljanz, psoriasis, moderate, severe, itch, nail psoriasis