A Study to Evaluate Safety and Efficacy of PF-06826647 For Moderate To Severe Plaque Psoriasis

Study Overview
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Brief Summary
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This multicenter study is being conducted to provide additional PF-06826647 safety and tolerability data, and to further explore the clinical efficacy of PF-06826647 in the treatment of moderate to severe plaque psoriasis. Additionally, the study is intended to enable selection of oral dose and dosing regimen for the future clinical development of PF-06826647.

Official Title
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A PHASE 2, RANDOMIZED, DOUBLE BLIND, PLACEBO-CONTROLLED, STUDY TO EVALUATE THE SAFETY AND EFFICACY OF PF-06826647 IN PARTICIPANTS WITH MODERATE TO SEVERE PLAQUE PSORIASIS

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: PF-06826647 or Placebo
* Drug: PF-06826647


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female between the ages of 18 and 75 years. Participants with a diagnosis of plaque psoriasis (psoriasis vulgaris) for at least 6 months. Have a PASI score of 12 or greater AND a Physician Global Assessment score of 3 (moderate) or 4 (severe). Have plaque-type psoriasis covering at least 10 % of total body surface area (BSA). Exclusion Criteria: Have non-plaque forms of psoriasis. Drug-induced psoriasis. Current active infection. Infected with Mycobacterium tuberculosis (TB). Have any history of malignancies. Require treatment with prohibited concomitant medications(s). Positive for hepatitis B or C, or human immunodeficiency virus (HIV).

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-06826647 Drug Dose Level 1<br>Delivered orally for 16 weeks during the Investigational Treatment Period | Drug: PF-06826647 or Placebo<br>* Delivered orally (tablet) once daily (QD) for 16 weeks during the Investigational Treatment Period<br>|
| Experimental: PF-06826647 Placebo<br>Delivered orally for 16 weeks during the Investigational Treatment Period | Drug: PF-06826647 or Placebo<br>* Delivered orally (tablet) once daily (QD) for 16 weeks during the Investigational Treatment Period<br>|
| Experimental: PF-06826647 Drug Dose Level 2<br>Delivered orally for 16 weeks during the Investigational Treatment Period | Drug: PF-06826647 or Placebo<br>* Delivered orally (tablet) once daily (QD) for 16 weeks during the Investigational Treatment Period<br>|
| Experimental: PF-06826647 Drug Dose Level 3<br>Delivered orally for 16 weeks during the Investigational Treatment Period then 24 weeks in Extension Period. | Drug: PF-06826647 or Placebo<br>* Delivered orally (tablet) once daily (QD) for 16 weeks during the Investigational Treatment Period<br>Drug: PF-06826647<br>* Delivered orally (tablet) once daily (QD) for 24 weeks during the Extension Period<br>|
| Experimental: PF-06826647 Drug Dose Level 4<br>Delivered orally for 16 weeks then for 24 weeks in Extension Period. | Drug: PF-06826647 or Placebo<br>* Delivered orally (tablet) once daily (QD) for 16 weeks during the Investigational Treatment Period<br>Drug: PF-06826647<br>* Delivered orally (tablet) once daily (QD) for 24 weeks during the Extension Period<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Psoriasis Area and Severity Index 90 (PASI 90) Response Up to Week 16 - Investigational Treatment Period | The PASI quantifies the severity of a participant's psoriasis based on both lesion severity and the percentage of body surface area (BSA) affected. PASI is a composite scoring by the investigator of degree of erythema, induration, and scaling (each scored separately) for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin], and lower limbs [including buttocks]), with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. PASI 90 response was defined as at least a 90% reduction in PASI relative to baseline. The statistical analysis was for the data at Week 16. | Baseline up to Week 16 | 
| Number of Participants With Treatment-Emergent Adverse Events (All-Causality), Week 16 to Week 40 - Extension Treatment Period | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious AE (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. In this outcome measure, an AE was considered treatment-emergent if the event started on or after the first dosing day and time/start time but before the last dose plus the lag time. | From Week 16 to Week 40 | 
| Number of Participants With Treatment-Emergent Adverse Events (Treatment Related), Week 16 to Week 40 - Extension Treatment Period | Treatment-related adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. Serious AE (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. In this outcome measure, an AE was considered treatment-emergent if the event started on or after the first dosing day and time/start time but before the last dose plus the lag time. Relatedness to investigational product (PF-06826647 or placebo) was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category. | From Week 16 to Week 40 | 
| Number of Participants With Laboratory Test Abnormality - Hematology (Normal Baseline), Week 16 to Week 40 - Extension Treatment Period | Following hematology parameters were analyzed for laboratory examination: hemoglobin (HGB), hematocrit, erythrocytes (Ery.), reticulocytes, Ery. mean corpuscular volume, Ery. mean corpuscular HGB, Ery. mean corpuscular HGB concentration, platelets, reticulocytes/erythrocytes, leukocytes, lymphocytes/leukocytes, neutrophils/leukocytes, basophils, basophils/leukocytes, eosinophils, eosinophils/leukocytes, monocytes, monocytes/leukocytes, activated partial thromboplastin time, prothrombin time, prothrombin international (Intl.) normalized ratio, neutrophils total count, and lymphocytes total count. LLN=lower limit of normal; ULN=upper limit of normal. | From Week 16 to Week 40 | 
| Number of Participants With Laboratory Test Abnormality - Chemistry (Normal Baseline), Week 16 to Week 40 - Extension Treatment Period | Following clinical chemistry parameters were analyzed for laboratory examination: bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, alkaline phosphatase, protein, albumin, blood urea nitrogen, urea, creatinine, urate, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, sodium, potassium, chloride, calcium, bicarbonate, glucose, creatine kinase, and cholesterol. | From Week 16 to Week 40 | 
| Number of Participants With Laboratory Test Abnormality - Urinalysis (Normal Baseline), Week 16 to Week 40 - Extension Treatment Period | Following urinalysis parameters were analyzed for laboratory examination: urine pH, urine glucose, urine ketones, urine protein, urine hemoglobin, urine urobilinogen, urine bilirubin, urine nitrite, urine leukocyte esterase, urine erythrocytes, urine leukocytes, urine hyaline, and urine bacteria. | From Week 16 to Week 40 | 
| Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Criteria, Week 16 to Week 40 - Extension Treatment Period | Criteria for ECG abnormalities: maximum increase PR interval increase from baseline (IFB): percent change (Pctchg) >=25 percent (%) for baseline value of >200 milliseconds (msec) and Pctchg>=50% for baseline value of <=200 msec for PR interval, a maximum IFB: Pctchg>=50%, maximum QTcF interval (Fridericia's Correction) of 450 msec to <=480 msec, 480 msec to <=500 msec and a maximum change of <30 change =<60 or >60 msec from baseline. | From Week 16 to Week 40 | 
| Number of Participants With Vital Sign Data Meeting Pre-defined Criteria, Week 16 to Week 40 - Extension Treatment Period | The vital signs were obtained with participant in the seated position, after having sat calmly for at least 5 minutes. Criteria for vital signs abnormalities: sitting diastolic blood pressure (BP) < 50 millimeter of mercury (mmHg), sitting diastolic BP change >= 20 mmHg increase, sitting diastolic BP change >= 20 mmHg decrease, sitting systolic BP < 90 mmHg, sitting systolic BP change >= 30 mmHg increase, and sitting systolic BP change >= 30 mmHg decrease. | From Week 16 to Week 40 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Psoriasis Area and Severity Index 75 (PASI 75) Response Up to Week 16 - Investigational Treatment Period | The PASI quantifies the severity of a participant's psoriasis based on both, lesion severity and the percent of body surface area (BSA) affected. PASI is a composite scoring by the investigator of degree of erythema, induration, and scaling (each scored separately) for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin], and lower limbs [including buttocks]), with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. PASI 75 response was defined as at least a 75 percent (%) reduction in PASI relative to Baseline. The statistical analysis was for the data at Week 16. | Baseline up to Week 16 | 
| Percentage of Participants With Physician Global Assessment (PGA) of Psoriasis Score of Clear or Almost Clear and >=2 Points Improvement Up to Week 16 - Investigational Treatment Period | The PGA of psoriasis is 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 are 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 (0=clear; 1=almost clear; 2=mild; 3=moderate; and 4=severe). The statistical analysis was for the data at Week 16. | Baseline up to Week 16 | 
| Percentage of Participants With Physician Global Assessment (PGA) of Psoriasis Score of Clear or Almost Clear, Up to Week 16 - Investigational Treatment Period | The PGA of psoriasis is 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 are 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 (0=clear; 1=almost clear; 2=mild; 3=moderate; and 4=severe). PGA response was defined as 0 (clear) or 1 (almost clear). The statistical analysis was for the data at Week 16. | Baseline up to Week 16 | 
| Percentage of Participants With a Psoriasis Area and Severity Index 50 (PASI 50) Response Up to Week 16 - Investigational Treatment Period | The PASI quantifies the severity of a participant's psoriasis based on both, lesion severity and percent of BSA affected. PASI is a composite scoring by the investigator of degree of erythema, induration, and scaling (each scored separately) for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin], and lower limbs [including buttocks]), with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. PASI 50 response was defined as at least 50% reduction in PASI relative to Baseline. | Baseline up to Week 16 | 
| Percentage of Participants With a Psoriasis Area and Severity Index 100 (PASI 100) Response Up to Week 16 - Investigational Treatment Period | The PASI quantifies the severity of a participant's psoriasis based on both, lesion severity and the percent of body surface area (BSA) affected. PASI is a composite scoring by the investigator of degree of erythema, induration, and scaling (each scored separately) for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin], and lower limbs [including buttocks]), with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. PASI 100 response was defined as at least a 100 percent (%) reduction in PASI relative to Baseline. | Baseline up to Week 16 | 
| Change From Baseline in Psoriasis Area and Severity Index (PASI) Scores, Up to Week 16 - Investigational Treatment Period | 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= 90-100%. 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); total possible score range: 0= no disease to 72= maximal disease. The statistical analysis was for the data at Week 16. | Baseline up to Week 16 | 
| Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Scores, Up to Week 16 - Investigational Treatment Period | 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= 90-100%. 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); total possible score range: 0= no disease to 72= maximal disease. The statistical analysis was for the data at Week 16. | Baseline up to Week 16 | 
| Change From Baseline in Peak-Pruritus Numerical Rating Scale (PP-NRS) Scores, Up to Week 16 - Investigational Treatment Period | The intensity of pruritus was assessed by a PP-NRS, an 11-category numeric rating scale from 0 to 10, which was participant reported. Participants were asked to assess their itch over the past 24 hours, anchored by the terms no itch (0) and worst itch imaginable (10) at the ends. The statistical analysis was for the data at Week 16. | Baseline up to Week 16 | 
| Percentage of Participants Achieving Psoriasis Symptom Inventory (PSI) Response of Not at All or Mild on Every Item, Up to Week 16 - Investigational Treatment Period | The Psoriasis Symptom Inventory (PSI) is a self administered 8-item questionnaire that measures the severity of psoriasis symptoms over the past 24 hours and the past 7 days. The measure includes concepts of itch, pain, burning, stinging, cracking, scaling, flaking, and redness. Participants were asked to respond to each item using a 5-point Likert response scale: 0: not all severe, 1: mild, 2: moderate, 3: severe and 4: very severe. The statistical analysis was for the data at Week 16. | Baseline up to Week 16 | 
| Change From Baseline in Psoriasis Symptom Inventory (PSI) Up to Week 16 - Investigational Treatment Period | The Psoriasis Symptom Inventory (PSI) is a self administered 8-item questionnaire that measures the severity of psoriasis symptoms over the past 24 hours and the past 7 days. The measure includes concepts of itch, pain, burning, stinging, cracking, scaling, flaking, and redness. Participants were asked to respond to each item using a 5-point Likert response scale: 0: not all severe, 1: mild, 2: moderate, 3: severe and 4: very severe. The outcome of PSI is the sum of the scores for the 8 items. The total score range of PSI is 0-32. A negative change from baseline means a better outcome and the bigger score decrease means a better outcome. The statistical analysis was for the data at Week 16. | Baseline up to Week 16 | 
| Number of Participants With Treatment-Emergent Adverse Events (All-Causality), Up to Week 16 - Investigational Treatment Period | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious AE (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. In this outcome measure, an AE was considered treatment-emergent if the event started on or after the first dosing day and time/start time but before the last dose plus the lag time. | Baseline up to Week 16 | 
| Number of Participants With Treatment-Emergent Adverse Events (Treatment Related), Up to Week 16 - Investigational Treatment Period | Treatment-related adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug ((PF-06826647 or placebo). Serious adverse event (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. In this outcome measure, an AE was considered treatment-emergent if the event started on or after the first dosing day and time/start time but before the last dose plus the lag time. Relatedness to investigational product (PF-06826647 or placebo) was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category. | Baseline up to Week 16 | 
| Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Criteria, Up to Week 16 - Investigational Treatment Period | Criteria for ECG abnormalities: Criteria for ECG abnormalities: maximum PR interval >=300 milliseconds (msec) and maximum increase PR interval increase from baseline (IFB): percent change (Pctchg) >=25 percent (%) for baseline value of >200 msec and Pctchg>=50% for baseline value of <=200 msec for PR interval, maximum QRS interval >=140 msec and a maximum IFB: Pctchg>=50%, maximum QTcF interval (Fridericia's Correction) of 450 msec to <=480 msec, 480 msec to <=500 msec and a maximum change of <30change<=60 or >60 msec from baseline. | Baseline up to Week 16 | 
| Number of Participants With Vital Sign Data Meeting Pre-defined Criteria, Up to Week 16 - Investigational Treatment Period | The vital signs were obtained with participant in the seated position, after having sat calmly for at least 5 minutes. Criteria for vital signs abnormalities: pulse rate >120 beats per minute (BPM), sitting diastolic blood pressure (BP) change >=20 millimeter of mercury (mmHg) increase, sitting diastolic BP change >=20 mmHg decrease, sitting systolic BP <90 mmHg, sitting systolic BP change >=30 mmHg increase, and sitting systolic BP change >=30 mmHg decrease. | Baseline up to Week 16 | 
| Number of Participants With Laboratory Test Abnormality - Hematology (Normal Baseline), Up to Week 16 - Investigational Treatment Period | Following hematology parameters were analyzed for laboratory examination: hemoglobin (HGB), hematocrit, erythrocytes (Ery.), reticulocytes, Ery. mean corpuscular volume, Ery. mean corpuscular HGB, Ery. mean corpuscular HGB concentration, platelets, reticulocytes/erythrocytes, leukocytes, lymphocytes/leukocytes, neutrophils/leukocytes, basophils, basophils/leukocytes, eosinophils, eosinophils/leukocytes, monocytes, monocytes/leukocytes, activated partial thromboplastin time, prothrombin time, neutrophils total count, and lymphocytes total count. LLN=lower limit of normal; ULN=upper limit of normal. | Baseline up to Week 16 | 
| Number of Participants With Laboratory Test Abnormality - Chemistry (Normal Baseline), Up to Week 16 - Investigational Treatment Period | Following clinical chemistry parameters were analyzed for laboratory examination: bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, alkaline phosphatase, protein, albumin, blood urea nitrogen, urea, creatinine, urate, high-density lipoprotein (HDL) cholesterol, triglycerides, sodium, potassium, chloride, calcium, bicarbonate, glucose, creatine kinase, and cholesterol. LLN=lower limit of normal; ULN=upper limit of normal. | Baseline up to Week 16. | 
| Number of Participants With Laboratory Test Abnormality - Urinalysis (Normal Baseline), Up to Week 16 - Investigational Treatment Period | Following urinalysis parameters were analyzed for laboratory examination: urine pH, urine glucose, urine ketones, urine protein, urine hemoglobin, urine urobilinogen, urine bilirubin, urine nitrite, urine leukocyte esterase, urine erythrocytes, urine leukocytes, urine hyaline, and urine bacteria. | Baseline up to Week 16 |