Study to Evaluate PF-04965842 in Patients With Moderate to Severe Psoriasis

Study Overview
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Brief Summary
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Study B7451005 is a Phase 2 study which will assess the efficacy and safety of PF-04965842 in patients with moderate to severe psoriasis. The study will include three PF-04965842 groups (200 mg daily, 400 mg daily and 200 mg twice daily) and a placebo group. The treatment period will be 4 weeks in duration and will be followed up by a 4 week follow up period.

Official Title
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A Phase 2, Randomized, Double-blind, Placebo-controlled Study To Evaluate Safety And Efficacy Of Pf-04965842 In Subjects With Moderate To Severe Psoriasis

Conditions
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Plaque Psoriasis

Intervention / Treatment
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* Drug: PF-04965842
* Drug: PF-04965842
* Drug: PF-04965842
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of plaque psoriasis for at least 6 months prior to first study dose. Have plaque type psoriasis covering at least 15% of total BSA at Day 1 (at the time of the first study dose). Have a PASI score of 12 or greater at Day 1 (at the time of the first study dose). Be a candidate for phototherapy or systemic treatment of psoriasis (either naïve or history of previous treatment). Exclusion Criteria: Currently have non plaque forms of psoriasis, eg, erythrodermic, guttate, or pustular psoriasis. 3. Have current drug induced psoriasis, eg, a new onset of psoriasis or an exacerbation of psoriasis from beta blockers, calcium channel blockers, antimalarial drugs or lithium. Have received any of the following treatment regimens specified in the timeframes outlined below: Within 9 months of first dose of study drug: • Ustekinumab (Stelara). Within 12 weeks of first dose of study drug: • Any experimental therapy for psoriasis or rheumatoid arthritis. Within 4 8 weeks of first dose of study drug: Biologic therapies for psoriasis have discontinuation periods determined from approximately 5x half life of the respective biologic: 4 weeks: etanercept (Enbrel). 8 weeks: infliximab (Remicade), adalimumab (Humira). Within 4 weeks of first dose of study drug: Systemic treatments other than biologics that could affect psoriasis (eg, oral or injectable corticosteroids, retinoids, methotrexate, cyclosporine, fumaric acid derivatives, sulfasalazine, hydroxycarbamide (hydroxyurea), azathioprine). Phototherapy and psoralen plus ultraviolet A therapy (PUVA). Other - intramuscular gold, immunization with any live virus vaccination (eg, FluMist), herbal medications. Within 2 weeks of first dose of study drug: Topical treatments that could affect psoriasis (eg, corticosteroids, tars, keratolytics, anthralin, vitamin D analogs, and retinoids). Phototherapy with ultraviolet B (UVB) (narrowband or broadband).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>200mg of PF-04965842 twice daily | Drug: PF-04965842<br>* Subjects will receive 200 mg PF 04965842 twice daily for 4 weeks<br>* Other names: JAK1 inhibitor;|
| Experimental: Cohort 2<br>400mg of PF-04965842 once daily | Drug: PF-04965842<br>* Subjects will receive 400 mg PF 04965842 daily for 4 weeks<br>* Other names: JAK1 inhibitor;|
| Experimental: Cohort 3<br>200mg of PF-04965842 once daily | Drug: PF-04965842<br>* Subjects will receive 200 mg PF 04965842 daily for 4 weeks<br>* Other names: JAK1 inhibitor;|
| Placebo Comparator: Cohort 4<br>Placebo comparator daily | Other: Placebo<br>* Subjects will receive placebo for 4 weeks<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 4 | PASI score is the combined assessment of lesion severity and area affected into single score range: 0 (no disease) to 72 (maximal disease), with higher scores representing greater severity of psoriasis. Body divided into 4 sections (head and neck [h], arms [u], trunk [t], legs [l]); each area scored by itself and scores combined for final PASI score. For each section, percent body surface area (A) of skin involved was estimated: 0 (no involvement) to 6 (90-100 percent involvement), severity estimated by clinical signs: erythema (E), induration (I), scaling (S); 5 point scale: 0 (no involvement) to 4 (very marked involvement). Final PASI score = 0.1Ah (Eh + Ih + Sh) + 0.2Au (Eu + Iu + Su) + 0.3At (Et + It + St) + 0.4Al (El + Il + Sl), where head: 0.1; upper limbs: 0.2; trunk: 0.3; lower limbs: 0.4). | Baseline, Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in PASI Score at Week 1, 2, 3, 4, 5, 6, and 8 | PASI score is the combined assessment of lesion severity and area affected into single score range: 0 (no disease) to 72 (maximal disease), with higher scores representing greater severity of psoriasis. Body divided into 4 sections (head and neck [h], arms [u], trunk [t], legs [l]); each area scored by itself and scores combined for final PASI score. For each section, percent body surface area (A) of skin involved was estimated: 0 (no involvement) to 6 (90-100 percent involvement), severity estimated by clinical signs: erythema (E), induration (I), scaling (S); 5 point scale: 0 (no involvement) to 4 (very marked involvement). Final PASI score = 0.1Ah (Eh + Ih + Sh) + 0.2Au (Eu + Iu + Su) + 0.3At (Et + It + St) + 0.4Al (El + Il + Sl), where head: 0.1; upper limbs: 0.2; trunk: 0.3; lower limbs: 0.4). | Baseline, Week 1, 2, 3, 4, 5, 6, 8 | 
| Change From Baseline in PASI Score at Week 1, 2, 3, 5, 6 and 8 | PASI score is the combined assessment of lesion severity and area affected into single score range: 0 (no disease) to 72 (maximal disease), with higher scores representing greater severity of psoriasis. Body divided into 4 sections (head and neck [h], arms [u], trunk [t], legs [l]); each area scored by itself and scores combined for final PASI score. For each section, percent body surface area (A) of skin involved was estimated: 0 (no involvement) to 6 (90-100 percent involvement), severity estimated by clinical signs: erythema (E), induration (I), scaling (S); 5 point scale: 0 (no involvement) to 4 (very marked involvement). Final PASI score = 0.1Ah (Eh + Ih + Sh) + 0.2Au (Eu + Iu + Su) + 0.3At (Et + It + St) + 0.4Al (El + Il + Sl), where head: 0.1; upper limbs: 0.2; trunk: 0.3; lower limbs: 0.4). | Baseline, Week 1, 2, 3, 5, 6, 8 | 
| Percentage of Participants Achieving 50 Percent Reduction From Baseline PASI Score at Week 1, 2, 3, 4, 5, 6, and 8 | PASI score is combined assessment of lesion severity and area affected into single score range:0 (no disease) to 72 (maximal disease), with higher scores representing greater severity of psoriasis. Body divided into 4 sections (head and neck [h], arms [u], trunk [t], legs [l]); each area scored by itself and scores combined for final PASI score. For each section, percent body surface area (A) of skin involved was estimated:0 (no involvement) to 6 (90-100 percent involvement), severity estimated by clinical signs: erythema (E), induration (I), scaling (S); 5 point scale: 0 (no involvement) to 4 (very marked involvement). Final PASI score = 0.1Ah (Eh + Ih + Sh) + 0.2Au (Eu + Iu + Su) + 0.3At (Et + It + St) + 0.4Al (El + Il + Sl), where head: 0.1; upper limbs: 0.2; trunk: 0.3; lower limbs: 0.4). Participants who had at least 50 percent reduction in PASI score relative to baseline PASI Score are reported. 90 percent confidence intervals are calculated using clopper-pearson (exact) method. | Baseline, Week 1, 2, 3, 4, 5, 6, 8 | 
| Percentage of Participants Achieving 75 Percent Reduction From Baseline PASI Score at Week 1, 2, 3, 4, 5, 6 and 8 | PASI score is combined assessment of lesion severity and area affected into single score range:0 (no disease) to 72 (maximal disease), with higher scores representing greater severity of psoriasis. Body divided into 4 sections (head and neck [h], arms [u], trunk [t], legs [l]); each area scored by itself and scores combined for final PASI score. For each section, percent body surface area (A) of skin involved was estimated:0 (no involvement) to 6 (90-100 percent involvement), severity estimated by clinical signs: erythema (E), induration (I), scaling (S); 5 point scale: 0 (no involvement) to 4 (very marked involvement). Final PASI score = 0.1Ah (Eh + Ih + Sh) + 0.2Au (Eu + Iu + Su) + 0.3At (Et + It + St) + 0.4Al (El + Il + Sl), where head: 0.1; upper limbs: 0.2; trunk: 0.3; lower limbs: 0.4). Participants who had at least 75 percent reduction in PASI score relative to baseline PASI Score are reported. 90 percent confidence intervals are calculated using clopper-pearson (exact) method. | Baseline, Week 1, 2, 3, 4, 5, 6, 8 | 
| Percentage of Participants Achieving 90 Percent Reduction From Baseline PASI Score at Week 1, 2, 3, 4, 5, 6, and 8 | PASI score is combined assessment of lesion severity and area affected into single score range:0 (no disease) to 72 (maximal disease), with higher scores representing greater severity of psoriasis. Body divided into 4 sections (head and neck [h], arms [u], trunk [t], legs [l]); each area scored by itself and scores combined for final PASI score. For each section, percent body surface area (A) of skin involved was estimated:0 (no involvement) to 6 (90-100 percent involvement), severity estimated by clinical signs: erythema (E), induration (I), scaling (S); 5 point scale: 0 (no involvement) to 4 (very marked involvement). Final PASI score = 0.1Ah (Eh + Ih + Sh) + 0.2Au (Eu + Iu + Su) + 0.3At (Et + It + St) + 0.4Al (El + Il + Sl), where head: 0.1; upper limbs: 0.2; trunk: 0.3; lower limbs: 0.4). Participants who had at least 90 percent reduction in PASI score relative to baseline PASI Score are reported. 90 percent confidence intervals are calculated using clopper-pearson (exact) method. | Baseline, Week 1, 2, 3, 4, 5, 6, 8 (early termination) | 
| Percentage of Participants Achieving Physician Global Assessment (PGA) Response of 'Clear' or 'Almost Clear' at Week 1, 2, 3, 4, 5, 6, and 8 | The PGA of psoriasis was scored on a 5-point scale, reflecting a global consideration of the erythema (E), induration (I), and scaling (S) across all psoriatic lesions. The severity rating scores (erythema: 0= no evidence of erythema to 4= dark, deep red; Induration: 0= no evidence of plaque elevation to 4= marked plaque elevation, hard/sharp borders; Scaling: 0= no evidence of scaling to 4= thick, coarse scale predominates) were summed (E + I + S= total) and the average (total/3) was taken. The total average was rounded to the nearest whole number score to determine the PGA. The 5-point scale for PGA was: 0= clear; 1= almost clear; 2= mild; 3= moderate; 4= severe, where higher score indicating more severity. Participants with response of clear and almost clear were reported. 90 percent confidence intervals were calculated using clopper-pearson (exact) method. | Week 1, 2, 3, 4, 5, 6, 8 | 
| Change From Baseline in Fasting Lipids at Week 2, 4 and 8 | Participants were required to fast 9 hours prior to sampling for lipid profile which included following parameters: low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), cholesterol, triglycerides. | Baseline, Week 2, 4, 8 (early termination) | 
| Change From Baseline in Lipid Ratios at Week 2, 4 and 8 | The ratio of LDL-C/HDL-C was reported. | Baseline, Week 2, 4, 8 (early termination) | 
| Change From Baseline in High Sensitivity C- Reactive Protein (hsCRP) at Week 1, 2, 3, 4, and 8 | The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. Reference range for measurements is 0-0.5 mg/dL and lower limit of detection is less than (<) 0.015 mg/dL. Any value <0.015 mg/dL is imputed as 0.0075 mg/dL. | Baseline, Week 1, 2, 3, 4, 8 (early termination) | 
| Number of Participants Reporting Clinically Significant Change From Baseline in Epstein-Barr Virus (EBV) Values | EBV samples were collected and changes from baseline were evaluated by the principal investigator (PI) for clinical significance. Clinical significance is levels outside of the normal range (abnormal levels) with clinically apparent viral disease, or that resulted in adverse event (AEs) or required follow-up. | Baseline up to Week 8 (early termination) | 
| Number of Participants Reporting Clinically Significant Change From Baseline in Cytomegalovirus (CMV) Values | CMV samples were collected and changes from baseline were evaluated by the PI for clinical significance. Clinical significance is levels outside of the normal range (abnormal levels) with clinically apparent viral disease, or that resulted in AEs or required follow-up. | Baseline up to Week 8 (early termination) | 
| Number of Participants Reporting Clinically Significant Change From Baseline in Herpes Simplex Virus Deoxyribonucleic Acid (HSV DNA) Values | HSV DNA samples were collected and changes from baseline were evaluated by the PI for clinical significance. Clinical significance is levels outside of the normal range (abnormal levels) with clinically apparent viral disease, or that resulted in AEs or required follow-up. | Baseline up to Week 8 (early termination) | 
| Change From Baseline in Blood Pressure (BP) at Week 1, 2, 3, 4, 5, 6, and 8 |  | Baseline, Week 1, 2, 3, 4, 5, 6, 8 (early termination) | 
| Change From Baseline in Pulse Rate at Week 1, 2, 3, 4, 5, 6, and 8 |  | Baseline, Week 1, 2, 3, 4, 5, 6, 8 (early termination) | 
| Change From Baseline in Respiratory Rate at Week 1, 2, 3, 4, 5, 6, and 8 |  | Baseline, Week 1, 2, 3, 4, 5, 6, 8 (early termination) | 
| Change From Baseline in Body Temperature at Week 1, 2, 3, 4, 5, 6, and 8 |  | Baseline, Week 1, 2, 3, 4, 5, 6, 8 (early termination) | 
| Number of Participants Reporting Clinically Significant Change From Baseline in Heart Rate |  | Baseline up to Week 8 (early termination) | 
| Number of Participants Reporting Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters | ECG change data was reported as qualitative results, as per change in planned analysis. It was categorized as: normal; abnormal, not clinically significant or abnormal, clinically significant. | Baseline up to Week 8 (early termination) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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JAK, Phase 2, randomized, double-blind, placebo, plaque, psoriasis, safety, efficacy, janus kinase, moderate, severe