Study To Evaluate Safety And Efficacy Of PF-06700841 In Subjects With Moderate To Severe Plaque Psoriasis

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether PF-06700841 is safe and effective in the treatment of chronic plaque psoriasis.

Official Title
-----------------
A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE SAFETY AND EFFICACY OF PF-06700841 IN SUBJECTS WITH MODERATE TO SEVERE PLAQUE PSORIASIS

Conditions
-----------------
Chronic Plaque Psoriasis

Intervention / Treatment
-----------------
* Drug: PF-06700841
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have had a diagnosis of plaque psoriasis (psoriasis vulgaris) for at least 6 months prior to Baseline/Day 1 (prior to first dose of study drug) Have a PASI score of 12 or greater AND a PGA score of 3 (moderate) or 4 (severe) at Baseline/Day 1 (prior to first dose of study drug) Have plaque-type psoriasis covering at least 10% of total body surface area (BSA) at Baseline/Day 1 (prior to first dose of study drug) Considered by dermatologist investigator to be a candidate for systemic therapy or phototherapy of psoriasis (either naïve or history of previous treatment) Exclusion Criteria: Currently have non-plaque forms of psoriasis, eg, erythrodermic, guttate, or pustular psoriasis, with the exception of nail psoriasis which is allowed Have evidence of skin conditions (eg, eczema) at the time of screening or baseline visit that would interfere with the evaluation of psoriasis Cannot discontinue systemic therapies and/or topical therapies for the treatment of psoriasis and cannot discontinue phototherapy (UVB or PUVA) Have previously been treated with Secukinumab (Cosentyx), and Ixekizumab (Taltz). Have taken Apremilast (Otezla) within 3 months of first dose of study drug. Have undergone treatment with tofacitinib within 3 months of first dose.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-06700841 60 mg followed by 30 mg once daily<br>4 week induction with 60 mg PF-06700841 once daily, followed by 8 week chronic administration of 30 mg PF-06700841 once daily | Drug: PF-06700841<br> <br> |
| Experimental: PF-06700841 60 mg followed by 10 mg once daily<br>4 week induction with 60 mg PF-06700841 once daily, followed by 8 week chronic administration of 10 mg PF-06700841 once daily | Drug: PF-06700841<br> <br> |
| Experimental: PF-06700841 60mg once daily followed by 100mg once weekly<br>4 week induction with 60 mg PF-06700841 once daily, followed by 8 week chronic administration of 100 mg PF-06700841 once weekly | Drug: PF-06700841<br> <br> |
| Experimental: PF-06700841 60mg once daily followed by placebo once daily<br>4 week induction with 60 mg PF-06700841 once daily, followed by 8 week chronic administration of placebo once daily | Drug: PF-06700841<br> <br> |
| Experimental: PF-06700841 30mg once daily<br>4 week induction with 30 mg PF-06700841 once daily followed by 8 week chronic administration of 30 mg PF-06700841 once daily | Drug: PF-06700841<br> <br> |
| Experimental: PF-06700841 30mg once daily followed by 10mg once daily<br>4 week induction with 30 mg PF-06700841 once daily, followed by 8 week chronic administration of 10 mg PF-06700841 once daily | Drug: PF-06700841<br> <br> |
| Experimental: PF-06700841 30mg once daily followed by 100mg once weekly<br>4 week induction with 30 mg PF-06700841 once daily, followed by 8 week chronic administration of 100 mg PF-06700841 once weekly | Drug: PF-06700841<br> <br> |
| Placebo Comparator: Placebo<br>12 weeks once daily placebo | Other: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Psoriasis Area and Severity Index (PASI) Score at Week 12 | The PASI quantifies the severity of a participant's psoriasis based on both lesion severity and the percentage of body surface area (BSA) affected. In each area, the sum of the severity rating scores for erythema, induration and scaling is multiplied by the score representing the percentage of this area involved by psoriasis, multiplied by a weighting factor (head 0.1; upper limbs 0.2; trunk 0.3; lower limbs 0.4). The sum of the numbers obtained for each of the four body areas is the PASI. The PASI score can vary in increments of 0.1 units from 0.0 to 72.0, with higher scores representing increasing severity of psoriasis. | Baseline (Day 1 pre-dose), Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving a Psoriasis Area and Severity Index 75 (PASI75) Response at Week 12 | A PASI75 response is a 75% or greater reduction from baseline in PASI score. The PASI score can vary in increments of 0.1 units from 0.0 to 72.0, with higher scores representing increasing severity of psoriasis. | Week 12 | 
| Change From Baseline in PASI Scores at Week 4 by Induction Dose | Change from baseline in PASI scores at Week 4 was presented by induction dose (ie, PF-06700841 60 mg QD, 30 mg QD, and placebo). The PASI score can vary in increments of 0.1 units from 0.0 to 72.0, with higher scores representing increasing severity of psoriasis. | Baseline (Day 1 pre-dose), Week 4 | 
| Percentage of Participants Achieving PASI75 Responses at Weeks 1, 2, 4, 6, 8, 10, 14, 16 | A PASI75 response is a 75% or greater reduction from baseline in PASI score. The PASI score can vary in increments of 0.1 units from 0.0 to 72.0, with higher scores representing increasing severity of psoriasis. | Weeks 1, 2, 4, 6, 8, 10, 14, 16 | 
| Percentage of Participants Achieving a Psoriasis Area and Severity Index 50 (PASI50) Response at Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 | A PASI50 response is a 50% or greater reduction from baseline in PASI score. The PASI score can vary in increments of 0.1 units from 0.0 to 72.0, with higher scores representing increasing severity of psoriasis. | Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 | 
| Percentage of Participants Achieving a Psoriasis Area and Severity Index 90 (PASI90) Response at Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 | A PASI90 response is a 90% or greater reduction from baseline in PASI score. The PASI score can vary in increments of 0.1 units from 0.0 to 72.0, with higher scores representing increasing severity of psoriasis. | Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 | 
| Change From Baseline in PASI Scores at Weeks 1, 2, 4, 6, 8, 10, 14, 16 | The PASI score can vary in increments of 0.1 units from 0.0 to 72.0, with higher scores representing increasing severity of psoriasis. | Baseline (Day 1 pre-dose), Weeks 1, 2, 4, 6, 8, 10, 14, 16 | 
| Percent Change From Baseline in PASI Scores at Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 | The PASI score can vary in increments of 0.1 units from 0.0 to 72.0, with higher scores representing increasing severity of psoriasis. | Baseline (Day 1 pre-dose), Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 | 
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE (non-serious and serious) was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or an important medical event. Any such events with initial onset or increasing in severity after the first dose of study treatment were counted as treatment-emergent. | From first dose of study treatment (Day 1) up to Week 20 | 
| Number of Participants Who Discontinued From the Study Due to Treatment-Emergent AEs | The number of participants who discontinued from the study due to treatment-emergent AEs is presented. Note for data reported under this Outcome Measure: Per sponsor reporting standard, pregnancy was counted as AE for AE data tables while it was counted separately in the disposition data table (Participant Flow Module). | From first dose of study treatment (Day 1) up to Week 20 | 
| Change From Baseline in Blood Lipid Level at Weeks 4 and 12 | Lipid panel included low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, total cholesterol, and triglycerides. | Baseline (Day 1 pre-dose), Weeks 4 and 12 | 
| Number of Participants With Any Post-Baseline Laboratory Test Abnormalities | Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology (hemoglobin, hematocrit, erythrocytes, reticulocytes, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time, prothrombin time [PT], PT/international normalized ratio; chemistry (total bilirubin, direct bilirubin, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase, protein, albumin, urea nitrogen, creatinine, urate, total cholesterol, LDL and HDL cholesterol, triglycerides, calcium, sodium, potassium, chloride, bicarbonate, glucose, creatine kinase, Cystatin C, glomerular filtration rate; urinalysis (pH, urine glucose, ketones, urine protein, urine hemoglobin, nitrites, leukocyte esterase, urine erythrocytes, urine leukocytes, hyaline casts, bacteria, choriogonadotropin beta). | From first dose of study treatment (Day 1) up to Week 16 | 
| Number of Participants With Post-Baseline Vital Sign Abnormalities | Vital signs categorical summarization criteria: 1) sitting systolic blood pressure (SBP) <90 millimeters of mercury (mmHg); 2) sitting diastolic blood pressure (DBP) <50 mmHg; 3) sitting pulse rate <40 or >120 beats per minute (bpm); 4) change from baseline (increase or decrease) in sitting DBP greater than or equal to (>=) 20 mmHg; 5) change from baseline (increase or decrease) in sitting SBP >=30 mmHg. | From first dose of study treatment (Day 1) up to Week 16 | 
| Number of Participants With Post-Baseline Electrocardiogram (ECG) Abnormalities | ECG categorical summarization criteria: 1) QRS duration (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): >=140 milliseconds (msec), >=50% change from baseline; 2) PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): >=300 msec, >=25% change when baseline is > 200 msec or >=50% change when baseline is less than or equal to (<=) 200 msec; 3) QT interval (time from ECG Q wave to the end of the T wave corresponding to electrical systole): absolute value of >=500 msec; 4) QTc interval (QT corrected for heart rate): absolute value of 450 to <480 msec, 480 to <500 msec, >=500 msec; a change from baseline of 30 to <60 msec or >=60 msec. | From first dose of study treatment (Day 1) up to Week 16 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
plaque psoriasis