Dose Ranging Study To Assess Efficacy, Safety and Tolerability Of PF-06700841 Topical Cream In Psoriasis

Study Overview
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Brief Summary
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This is a Phase 2b, randomized, double blind, vehicle controlled, parallel group, multicenter study in participants with mild to moderate plaque psoriasis. The duration of study participation will be approximately 22 weeks, including up to a 6 week screening period, 12 week treatment period, and approximately 4 week follow up period. Approximately 280 participants are planned to be randomized into the study.

Official Title
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A PHASE 2B, RANDOMIZED, DOUBLE BLIND, VEHICLE CONTROLLED, PARALLEL-GROUP, DOSE RANGING STUDY TO ASSESS EFFICACY, SAFETY, TOLERABILITY AND PHARMACOKINETICS OF PF-06700841 TOPICAL CREAM APPLIED ONCE OR TWICE DAILY FOR 12 WEEKS IN PARTICIPANTS WITH MILD TO MODERATE CHRONIC PLAQUE PSORIASIS

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: PF-06700841
* Drug: Vehicle (Placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: plaque psoriasis for 6 months PGA score mild or moderate body surface area (BSA) 2-15% Exclusion Criteria: other skin conditions that would interfere with the evaluation of psoriasis history of herpes zoster or simplex Infected with Mycobacterium tuberculosis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 |
| --- | --- |
| Placebo Comparator: Vehicle cream QD<br>Vehicle cream applied once daily (QD) | Drug: Vehicle (Placebo)<br>* Vehicle topical cream<br>|
| Experimental: PF-06700841 0.1% cream QD<br>PF-06700841 0.1% cream applied once daily (QD) | Drug: PF-06700841<br>* PF-06700841 topical cream<br>|
| Experimental: PF-06700841 0.3% cream QD<br>PF-06700841 0.3% cream applied once daily (QD) | Drug: PF-06700841<br>* PF-06700841 topical cream<br>|
| Experimental: PF-06700841 1% cream QD<br>PF-06700841 1% cream applied once daily (QD) | Drug: PF-06700841<br>* PF-06700841 topical cream<br>|
| Experimental: PF-06700841 3% cream QD<br>PF-06700841 3% cream applied once daily (QD) | Drug: PF-06700841<br>* PF-06700841 topical cream<br>|
| Experimental: PF-06700841 0.3% cream BID<br>PF-06700841 0.3% cream applied twice daily (BID) | Drug: PF-06700841<br>* PF-06700841 topical cream<br>|
| Experimental: PF-06700841 1% cream BID<br>PF-06700841 1% cream applied twice daily (BID) | Drug: PF-06700841<br>* PF-06700841 topical cream<br>|
| Placebo Comparator: Vehicle cream BID<br>Vehicle cream applied twice daily (BID) | Drug: Vehicle (Placebo)<br>* Vehicle topical cream<br>|
| Experimental: PF-06700841 3% cream BID<br>PF-06700841 3% cream applied twice daily (BID) | Drug: PF-06700841<br>* PF-06700841 topical cream<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Psoriasis Area and Severity Index (PASI) Score at Week 12 | The Psoriasis Area and Severity Index (PASI) score (0-72, with higher score representing greater severity) is a measurement of the severity and extent of psoriasis. The four regions of the body parts are head (10%), arms (20%), trunk (30%) and legs (40%). In each region, the area is expressed as a score of 0 (nothing), 1 (1-9%), 2 (10-29%), 3 (30-49%), 4 (50-69%), 5 (70-89%) or 6 (90-100%). Within each area, the degree of severity for erythema, induration and scaling are estimated between 0 and 4, with 4 being the highest severity. The final score combines disease severity and effected body surface area (BSA) from for four regions using the formula PASI =0.1Ah(Eh + Ih + Sh) + 0.2Au(Eu + Iu + Su) + 0.3At(Et + It + St) + 0.4Al(El + Il + Sl) where A = Area Score; E = erythema; I =induration; S = scaling; h = head; u = upper limbs; t = trunk; l = lower limbs. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Physician Global Assessment (PGA) Score Clear (0) or Almost Clear (1) and Greater Than or Equal to (>=) 2 Points Improvement From Baseline at Week 12 | PGA of psoriasis was scored on a 5-point scale, reflecting a global consideration of the erythema, induration, and scaling across all psoriatic lesions. Average erythema, induration, and scaling were scored separately over the whole body according to a 5-point severity scale (0 [no symptom] to 4 [severe symptom]). The total score was calculated as average of the 3 severity scores and rounded to the nearest whole number score to determine the PGA score and category. Scale for PGA: 0= clear, 1= almost clear, 2= mild, 3= moderate and 4= severe. Higher scores indicate more severity. | Baseline, Week 12 | 
| Percentage of Participants With 75% Reduction From Baseline in PASI at Week 1, 2, 4, 6, 8, 10, 12, 14, and 16 | The PASI score (0-72, with higher score representing greater severity) is a measurement of the severity and extent of psoriasis. The four regions of the body parts are head (10%), arms (20%), trunk (30%) and legs (40%). In each region, the area is expressed as a score of 0 (nothing), 1 (1-9%), 2 (10-29%), 3 (30-49%), 4 (50-69%), 5 (70-89%) or 6 (90-100%). Within each area, the degree of severity for erythema, induration and scaling are estimated between 0 and 4, with 4 being the highest severity. The final score combines disease severity and effected BSA from for four regions using the formula PASI =0.1Ah(Eh + Ih + Sh) + 0.2Au(Eu + Iu + Su) + 0.3At(Et + It + St) + 0.4Al(El + Il + Sl) where A = Area Score; E = erythema; I =induration; S = scaling; h = head; u = upper limbs; t = trunk; l = lower limbs. | Baseline, Week 1, 2, 4, 6, 8, 10, 12, 14, and 16 | 
| Change From Baseline in PASI Scores at Week 1, 2, 4, 6, 8, 10 and 12 | The PASI score (0-72, with higher score representing greater severity) is a measurement of the severity and extent of psoriasis. The four regions of the body parts are head (10%), arms (20%), trunk (30%) and legs (40%). In each region, the area is expressed as a score of 0 (nothing), 1 (1-9%), 2 (10-29%), 3 (30-49%), 4 (50-69%), 5 (70-89%) or 6 (90-100%). Within each area, the degree of severity for erythema, induration and scaling are estimated between 0 and 4, with 4 being the highest severity. The final score combines disease severity and effected BSA from for four regions using the formula PASI =0.1Ah(Eh + Ih + Sh) + 0.2Au(Eu + Iu + Su) + 0.3At(Et + It + St) + 0.4Al(El + Il + Sl) where A = Area Score; E = erythema; I =induration; S = scaling; h = head; u = upper limbs; t = trunk; l = lower limbs. | Baseline, Week 1, 2, 4, 6, 8, 10 and 12 | 
| Change From Baseline in PASI Scores at Week 14 and 16 | The PASI score (0-72, with higher score representing greater severity) is a measurement of the severity and extent of psoriasis. The four regions of the body parts are head (10%), arms (20%), trunk (30%) and legs (40%). In each region, the area is expressed as a score of 0 (nothing), 1 (1-9%), 2 (10-29%), 3 (30-49%), 4 (50-69%), 5 (70-89%) or 6 (90-100%). Within each area, the degree of severity for erythema, induration and scaling are estimated between 0 and 4, with 4 being the highest severity. The final score combines disease severity and effected BSA from for four regions using the formula PASI =0.1Ah(Eh + Ih + Sh) + 0.2Au(Eu + Iu + Su) + 0.3At(Et + It + St) + 0.4Al(El + Il + Sl) where A = Area Score; E = erythema; I =induration; S = scaling; h = head; u = upper limbs; t = trunk; l = lower limbs. | Baseline, Week 14 and 16 | 
| Percent Change From Baseline in PASI Scores at Week 1, 2, 4, 6, 8, 10 and 12 | The PASI score (0-72, with higher score representing greater severity) is a measurement of the severity and extent of psoriasis. The four regions of the body parts are head (10%), arms (20%), trunk (30%) and legs (40%). In each region, the area is expressed as a score of 0 (nothing), 1 (1-9%), 2 (10-29%), 3 (30-49%), 4 (50-69%), 5 (70-89%) or 6 (90-100%). Within each area, the degree of severity for erythema, induration and scaling are estimated between 0 and 4, with 4 being the highest severity. The final score combines disease severity and effected BSA from for four regions using the formula PASI =0.1Ah(Eh + Ih + Sh) + 0.2Au(Eu + Iu + Su) + 0.3At(Et + It + St) + 0.4Al(El + Il + Sl) where A = Area Score; E = erythema; I =induration; S = scaling; h = head; u = upper limbs; t = trunk; l = lower limbs. | Baseline, Week 1, 2, 4, 6, 8, 10 and 12 | 
| Percent Change From Baseline in PASI Scores at Week 14 and 16 | The PASI score (0-72, with higher score representing greater severity) is a measurement of the severity and extent of psoriasis. The four regions of the body parts are head (10%), arms (20%), trunk (30%) and legs (40%). In each region, the area is expressed as a score of 0 (nothing), 1 (1-9%), 2 (10-29%), 3 (30-49%), 4 (50-69%), 5 (70-89%) or 6 (90-100%). Within each area, the degree of severity for erythema, induration and scaling are estimated between 0 and 4, with 4 being the highest severity. The final score combines disease severity and effected BSA from for four regions using the formula PASI =0.1Ah(Eh + Ih + Sh) + 0.2Au(Eu + Iu + Su) + 0.3At(Et + It + St) + 0.4Al(El + Il + Sl) where A = Area Score; E = erythema; I =induration; S = scaling; h = head; u = upper limbs; t = trunk; l = lower limbs. | Baseline, Week 14 and 16 | 
| Absolute Peak-Pruritus Numerical Rating Scale (PP-NRS) Score at Baseline, Week 1, 2, 4, 6, 8, 10 and 12 | Participants were asked to assess their itch intensity over the past 24 hours, on a scale from 0 (no itching) to 10 (worst possible itching). Higher scores indicated worse itch. | Baseline, Week 1, 2, 4, 6, 8, 10 and 12 | 
| Absolute PP-NRS Score at Week 14 and 16 | Participants were asked to assess their itch intensity over the past 24 hours, on a scale from 0 (no itching) to 10 (worst possible itching). Higher scores indicated worse itch. | Week 14 and 16 | 
| Change From Baseline in PP-NRS Score at Week 1, 2, 4, 6, 8, 10 and 12 | Participants were asked to assess their itch intensity over the past 24 hours, on a scale from 0 (no itching) to 10 (worst possible itching). Higher scores indicated worse itch. | Baseline, Week 1, 2, 4, 6, 8, 10 and 12 | 
| Change From Baseline in PP-NRS Score at Week 14 and 16 | Participants were asked to assess their itch intensity over the past 24 hours, on a scale from 0 (no itching) to 10 (worst possible itching). Higher scores indicated worse itch. | Baseline, Week 14 and 16 | 
| Absolute Psoriasis Symptom Inventory (PSI) Score at Baseline, Week 1, 2, 4, 6, 8, 10, 12, 14 and 16, Early Termination (ET), ET Follow-up Visit 1 and 2 | PSI was a self-administered 8-item questionnaire that measured the severity of psoriasis symptoms over the past 24 hours and the past 7 days. PSI included following 8 items: itch, pain, burning, stinging, cracking, scaling, flaking, and redness. Each item was rated on a scale from 0 to 4, where 0= not at all severe, 1= mild, 2= moderate, 3= severe and 4= very severe. Scores from all items were summed to give PSI score range from 0 (no severity) to 32 (maximum severity), higher PSI score indicated greater severity. | Baseline, Week 1, 2, 4, 6, 8, 10, 12, 14 and 16, ET (Prior to Week 12), ET Follow-up Visit 1 (2 weeks post ET) and 2 (4 weeks post ET) | 
| Change From Baseline in PSI Score at Week 1, 2, 4, 6, 8, 10, 12, 14 and 16, ET, ET Follow-up Visit 1 and 2 | PSI was a self-administered 8-item questionnaire that measured the severity of psoriasis symptoms over the past 24 hours and the past 7 days. PSI included following 8 items: itch, pain, burning, stinging, cracking, scaling, flaking, and redness. Each item was rated on a scale from 0 to 4, where 0= not at all severe, 1= mild, 2= moderate, 3= severe and 4= very severe. Scores from all items were summed to give PSI score range from 0 (no severity) to 32 (maximum severity), higher PSI score indicated greater severity. | Baseline, Week 1, 2, 4, 6, 8, 10, 12, 14 and 16, ET (Prior to Week 12), ET Follow-up Visit 1 (2 weeks post ET) and 2 (4 weeks post ET) | 
| Percentage of Participants With PGA Score Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Week 1, 2, 4, 6, 8, 10, 14, and 16 | PGA of psoriasis was scored on a 5-point scale, reflecting a global consideration of the erythema, induration, and scaling across all psoriatic lesions. Average erythema, induration, and scaling were scored separately over the whole body according to a 5-point severity scale (0 [no symptom] to 4 [severe symptom]). The total score was calculated as average of the 3 severity scores and rounded to the nearest whole number score to determine the PGA score and category. Scale for PGA: 0= clear, 1= almost clear, 2= mild, 3= moderate and 4= severe. Higher scores indicate more severity. | Baseline, Week 1, 2, 4, 6, 8, 10, 14, and 16 | 
| Percentage of Participants Who Achieved PSI Score of 0 (Not at All) or 1 (Mild) on All Items at Week 1, 2, 4, 6, 8, 10, 12, 14, and 16 | PSI was a self-administered 8-item questionnaire that measured the severity of psoriasis symptoms over the past 24 hours and the past 7 days. PSI included following 8 items: itch, pain, burning, stinging, cracking, scaling, flaking, and redness. Each item was rated on a scale from 0 to 4, where 0= not at all severe, 1= mild, 2= moderate, 3= severe and 4= very severe. Scores from all items were summed to give PSI score range from 0 (no severity) to 32 (maximum severity), higher PSI score indicated greater severity. | Week 1, 2, 4, 6, 8, 10, 12, 14, and 16 | 
| Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment Related AEs and SAEs | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and all non-SAEs. Treatment emergent AEs (TEAEs) were events that occurred between first dose of study drug and up to 4 weeks after last dose that were absent before treatment or that worsened relative to pretreatment state. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator. | Day 1 of study drug dose to maximum of 4 weeks post last dose (maximum up to 16 weeks) | 
| Number of Participants With TEAEs by Severity | An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. AE was assessed according to severity; mild (not causing any significant problem, dose adjustment not required), moderate (caused problem that does not interfere significantly with usual activities or the clinical status, dose adjustment needed due to adverse event) and severe (caused problem that interfered significantly with usual activities or the clinical status, study drug stopped due to adverse event). | Day 1 of study drug dose to maximum of 4 weeks post last dose (maximum up to 16 weeks) | 
| Number of Participants Who Discontinued From Study Due to Adverse Events | An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. | Day 1 of study drug dose to maximum of 4 weeks post last dose (maximum up to 16 weeks) | 
| Number of Participants With Laboratory Abnormalities Meeting Specified Criteria | Bilirubin: greater than (>) 1.5* upper limit normal (ULN); aspartate aminotransferase, alanine aminotransferase: >2.5*ULN; creatinine, cystatin C: >1.3*ULN; creatine kinase: >2.0*ULN; glomerular filtration rate (GFR) CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) Equat: less than (<) 60 milliliter (mL)/minute (min)/1.73 meter(m)^2, greater than or equal to (>=) 30% decrease from baseline; GFR: <60 mL/min/1.73m^2. | Day 1 of study drug dose to maximum of 4 weeks post last dose (maximum up to 16 weeks) | 
| Number of Participants With Categorical Summary of Post-Baseline Electrocardiogram (ECG) Data | Following were ECG criteria used for categorical summary:1) PR interval: percentage change >=25/50%, QRS interval: value >140 msec, and QT interval corrected using the Fridericia's formula (QTcF): 450 msec < value less than equal to (<=) 480 and 30 < change <=60. | Post-baseline to Week 6, Post-baseline to Week 12 | 
| Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Following were the vital signs criteria: 1) Pulse rate: value <40 beats per min (bpm), value >120 bpm; 2) Sitting diastolic blood pressure (DBP): value <50 mmHg; change >=20 mmHg increase; change >=20 mmHg decrease; 3) Sitting systolic blood pressure (SBP): value <90 mmHg, change >=30 mmHg increase, change >=30 mmHg decrease; 4) Supine DBP: value <50 mmHg, change >=20 mmHg increase, change >=20 mmHg decrease; 5) Supine SBP: value <90 mmHg, change >=30 mmHg increase, change >=30 mmHg decrease. | Post-baseline to Week 12 | 
| Number of Participants Classified Per Skin Tolerability Assessment Severity Grades on Day 1, Week 1, 2, 4, 6, 8, 10, 12, 14, 16 | At the site of study drug application, skin tolerability was assessed for non-lesional skin surrounding the plaques on a scale from 0 to 4. Grade 0= none (no evidence of local intolerance), Grade 1= mild (minimal erythema and/or edema, slight glazed appearance), Grade 2= moderate (definite erythema and/or oedema with peeling and/or cracking but needs no adaptation of posology), Grade 3= severe, reported as AE (erythema, oedema glazing with fissures, few vesicles or papules: consider removing topical agent [if still in place]), Grade 4= very severe, reported as AE (strong reaction spreading beyond the treated area, bullous reaction, erosions: removal of topical agent [if still in place]). | Day 1, Week 1, 2, 4, 6, 8, 10, 12, 14, 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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psoriasis, topical