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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.