CP-690-550 Ointment For Chronic Plaque Psoriasis

Study Overview
=================
Brief Summary
-----------------
The study is being conducted to see whether CP-690,550 ointment has potential as a safe and effective treatment for adult patients with mild to moderate chronic plaque psoriasis.

Official Title
-----------------
A PHASE 2A, MULTI-SITE, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY OF THE PILOT EFFICACY, SAFETY, AND PHARMACOKINETICS OF 2 OINTMENT FORMULATIONS OF CP-690,550 IN SUBJECTS WITH MILD TO MODERATE CHRONIC PLAQUE PSORIASIS

Conditions
-----------------
Psoriasis

Intervention / Treatment
-----------------
* Drug: CP-690,550 Ointment 1
* Drug: Vehicle 1
* Drug: CP-690,550 Ointment 2
* Drug: Vehicle 2


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Mild to moderate chronic plaque psoriasis (psoriasis vulgaris), with the duration of at least 6 months; A target plaque of at least 9 sq. cm. Exclusion Criteria: Demonstrates rebound or flare of chronic plaque psoriasis; Non plaque form of psoriasis; Currently have or history of psoriatic arthritis; Current drug induced psoriasis; Currently on systemic therapy or was on systemic therapy for psoriasis within the previous 6 months; Currently on phototherapy for psoriasis or was on phototherapy within the previous 3 months

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group A<br> | Drug: CP-690,550 Ointment 1<br>* 2% CP-690,550 Ointment 1 twice daily for 4 weeks<br>|
| Placebo Comparator: Treatment Group B<br> | Drug: Vehicle 1<br>* Vehicle 1 twice daily for 4 weeks<br>|
| Experimental: Treatment Group C<br> | Drug: CP-690,550 Ointment 2<br>* 2% CP-690,550 Ointment 2 twice daily for 4 weeks<br>|
| Placebo Comparator: Treatment Group D<br> | Drug: Vehicle 2<br>* Vehicle 2 twice daily for 4 weeks<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Target Plaque Severity Score (TPSS) at Week 4 | Target plaque was evaluated individually for signs of induration, scaling and erythema. Each of the 3 signs was rated on 5-point severity scale ranged from 0 to 4: 0=none, 1=slight, 2=moderate, 3=marked, 4=very marked. The individual signs severity sub scores were summed to calculate TPSS. The total score varied in increments of 1 and ranged from 1 to 12, with higher scores representing greater severity of psoriasis. | Baseline, Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Target Plaque Severity Score (TPSS) at Weeks 1, 2 and 3 | Target plaque was evaluated individually for signs of induration, scaling and erythema. Each of the 3 signs was rated on 5-point severity scale ranged from 0 to 4: 0=none, 1=slight, 2=moderate, 3=marked, 4=very marked. The individual signs severity sub scores were summed to calculate TPSS. The total score varied in increments of 1 and ranged from 1 to 12, with higher scores representing greater severity of psoriasis. | Baseline, Weeks 1, 2, 3 | 
| Change From Baseline in Target Plaque Severity Score (TPSS) of Erythema, Induration and Scaling at Weeks 1, 2, 3 and 4 | Target plaque severity was evaluated individually for signs of induration, scaling and erythema. Each of the 3 signs was rated on 5-point severity scale ranged from 0 to 4: 0=none, 1=slight, 2=moderate, 3=marked, 4=very marked. | Baseline, Weeks 1, 2, 3, 4 | 
| Percentage of Participants With Treatment Area Overall Severity of Psoriasis Response of Clear (0) or Almost Clear (1) | Treatment area overall severity of psoriasis is global consideration of the erythema, induration and scaling across all psoriatic lesions, rated separately over the treatment area according to a 5-point severity scale ranged from 0 to 4: 0=none, 1=slight, 2=moderate, 3=marked, 4=very marked. The severity scores are summed and averaged after which the total average is rounded to the nearest whole number score to determine the treatment area overall severity of psoriasis score and category. Total possible score range: 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe. | Week 1, 2, 3, 4 | 
| Percentage of Participants Achieving Decrease From Baseline of Greater Than or Equal to 2 Points in Treatment Area Overall Severity of Psoriasis Score | Treatment area overall severity of psoriasis is global consideration of the erythema, induration and scaling across all psoriatic lesions, rated separately over the treatment area according to a 5-point severity scale ranged from 0 to 4: 0=none, 1=slight, 2=moderate, 3=marked, 4=very marked. The severity scores are summed and averaged after which the total average is rounded to the nearest whole number score to determine the treatment area overall severity of psoriasis score and category. Total possible score: 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe. | Week 1, 2, 3, 4 | 
| Percent Change From Baseline in Target Plaque Area at Week 1, 2, 3 and 4 | A tracing of the target plaque on transparent film was used to quantify the target plaque area. The target plaque area was calculated by image analysis (planimetry). At baseline, target plaque area was determined prior to randomization to confirm the target plaque size of at least 9 cm^2. | Baseline, Week 1, 2, 3, 4 | 
| Itch Severity Item (ISI) | The severity of itch was assessed using a single-item Patient Reported Outcome (PRO). Participants were asked to assess their worst itching due to psoriasis at the treatment area over the past 24 hours on a numeric rating scale ranging from of 0-10 where, 0=no itching and 10=worst possible itching. | Baseline, Week 1, 2, 3, 4 | 
| Change From Baseline in the Treatment Area Itch Severity Item (ISI) at Week 1, 2, 3 and 4 | The severity of itch was assessed using a single-item PRO. Participants were asked to assess their worst itching due to psoriasis at the treatment area over the past 24 hours on a numeric rating scale ranging from of 0-10 where, 0=no itching and 10=worst possible itching. | Baseline, Week 1, 2, 3, 4 | 
| Percentage of Participants in Each Patient Satisfaction With Study Medication (PSSM) Response Category | The PSSM evaluates overall participants satisfaction with the study treatment. Participants response evaluation was based on single 7-point item: 1=very satisfied, 2=somewhat satisfied, 3=slightly satisfied, 4=neither satisfied nor dissatisfied, 5=slightly dissatisfied, 6=somewhat dissatisfied, and 7=very dissatisfied. | Week 4 | 
| Number of Participants With Administration Site Adverse Events | An adverse event was any untoward medical occurrence attributed to study drug in a participant who received study drug. Application site adverse event included documentation of any clinically significant local reaction, e.g erosion, vesicles or scabbing. | Baseline up to follow up visit (Day 36-39 after last dose of study treatment) (up to maximum of 9.5 weeks) | 
| Number of Participants With Burning/Stinging of Psoriatic or Perilesional Skin in The Treatment Area | Burning/stinging symptoms at the treatment area including target plaque, additional plaque/s within the treatment area (if any) and treated perilesional skin (if any) were queried from the participants and scored by the investigator using a 4-point scale: 0=none; 1=Mild; 2=Moderate; 3=Severe. Except at baseline pre-dosing, burning/stinging was assessed for 2 time periods based on the maximum burning or stinging that the participant has experienced: Immediate (within 5 minutes after application); Persistent (beyond 5 minutes after application). | Baseline, Week 1, 2, 3, 4 | 
| Number of Participants With Draize Score of Perilesional Skin in The Treatment Area | Draize scoring evaluated perilesional skin within treatment area for erythema and presence/absence of other signs and symptoms. Erythema score ranged from 0 to 4 as: 0(no reaction visible), 1(trace reactions- barely perceptible pinkness), 2(mild reaction- readily visible pinkness), 3(moderate reaction- definite redness), 4 (Strong to severe reaction- very intense redness). Letter grade defined as: J(Burning, stinging, itching), E(Edema), P(Papules), V(Vesicles), B(Bulla reaction), S(Spreading), W(Weeping), I(Induration), XC(Additional comments). Superficial observations defined as: G(Glazing), Y(Peeling), C(Scab), D(Hyperpigmentation), H(Hypopigmentation), F(Fissuring), R(Erosion), U(Ulceration), K(Scaling). Erythema and other signs/symptoms with at least 1 participant with Draize Score of Perilesional Skin in the treatment area were reported in this outcome measure. | Baseline, Week 1, 2, 3, 4 | 
| Change From Baseline in Systolic and Diastolic Blood Pressure at Week 1, 2, 3, 4 | Blood pressure (BP) was measured in duplicate (approximately 5 minutes apart) using a standard calibrated BP measuring device. BP defined as pressure exerted by circulating blood upon walls of blood vessels. Diastolic BP is minimum pressure in arteries, near beginning of cardiac cycle when ventricles are filled with blood. Systolic BP is peak pressure in arteries, near end of the cardiac cycle when ventricles are contracting. Normal blood pressure is less than 120 millimeters of mercury (mmHg) systolic and less than 80 mmHg diastolic. Change=value at week 1, 2, 3, 4 minus value at baseline. | Baseline, Week 1, 2, 3, 4 | 
| Change From Baseline in Heart Rate at Week 1, 2, 3, 4 | Heart (pulse) rate was measured in duplicate (approximately 5 minutes apart) for a minimum of 30 seconds. Heart rate is the number of heartbeats per unit of time, usually per minute. The heart rate is based on the number of contractions of the ventricles (the lower chambers of the heart). Change=value at week 1, 2, 3, 4 minus value at baseline. | Baseline, Week 1, 2, 3, 4 | 
| Change From Baseline in Electrocardiogram (ECG) Findings at Week 4 | A single standard supine 12-lead Electrocardiogram (ECG) was performed after the participant had rested quietly for at least 10 minutes. ECG parameters included RR interval, PR interval, QRS complex, QT interval, QTcB (corrected for heart rate using Bazett's formula) interval, and QTcF (corrected for heart rate using Fridericia's formula) interval. | Baseline, Week 4 | 
| Change From Baseline in Hemoglobin Level at Week 2, 4 |  | Baseline, Week 2, 4 | 
| Change From Baseline in Platelet and Neutrophil Count at Week 2, 4 |  | Baseline, Week 2, 4 | 
| Change From Baseline in Creatinine Level at Week 2, 4 |  | Baseline, Week 2, 4 | 
| Change From Baseline in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Creatine Kinase (CK) Level at Week 2, 4 |  | Baseline, Week 2, 4 | 
| Plasma Concentration of CP-690,550 | Summary statistics were calculated by setting concentration values below the lower limit of quantification (lower limit of quantification=0.1 nanogram per milliliter [ng/mL]) to zero. Summary statistics were not presented if number of observations above lower limit of quantification (NALQ) = 0. | 0 (predose), 1, 2 and 4-9 hours postdose on Day 29 or early termination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Multi Site, Randomized, Placebo Controlled, Double Blind, Parallel Group, chronic plaque psoriasis, topical treatment, skin diseases, papulosquamous