Study to Evaluate PF-04965842 in Patients With Moderate to Severe Psoriasis
- Registration Number
- NCT02201524
- Lead Sponsor
- Pfizer
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 59
- 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).
- Currently have non plaque forms of psoriasis, eg, erythrodermic, guttate, or pustular psoriasis.
-
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 4 Placebo Placebo comparator daily Cohort 2 PF-04965842 400mg of PF-04965842 once daily Cohort 1 PF-04965842 200mg of PF-04965842 twice daily Cohort 3 PF-04965842 200mg of PF-04965842 once daily
- Primary Outcome Measures
Name Time Method Change From Baseline in Psoriasis Area and Severity Index (PASI) Score at Week 4 Baseline, 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).
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in PASI Score at Week 1, 2, 3, 4, 5, 6, and 8 Baseline, Week 1, 2, 3, 4, 5, 6, 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).
Change From Baseline in PASI Score at Week 1, 2, 3, 5, 6 and 8 Baseline, Week 1, 2, 3, 5, 6, 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).
Percentage of Participants Achieving 50 Percent Reduction From Baseline PASI Score at Week 1, 2, 3, 4, 5, 6, and 8 Baseline, Week 1, 2, 3, 4, 5, 6, 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.
Percentage of Participants Achieving 75 Percent Reduction From Baseline PASI Score at Week 1, 2, 3, 4, 5, 6 and 8 Baseline, Week 1, 2, 3, 4, 5, 6, 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.
Percentage of Participants Achieving 90 Percent Reduction From Baseline PASI Score at Week 1, 2, 3, 4, 5, 6, and 8 Baseline, Week 1, 2, 3, 4, 5, 6, 8 (early termination) 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.
Percentage of Participants Achieving Physician Global Assessment (PGA) Response of 'Clear' or 'Almost Clear' at Week 1, 2, 3, 4, 5, 6, and 8 Week 1, 2, 3, 4, 5, 6, 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.
Change From Baseline in Fasting Lipids at Week 2, 4 and 8 Baseline, Week 2, 4, 8 (early termination) 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.
Change From Baseline in Lipid Ratios at Week 2, 4 and 8 Baseline, Week 2, 4, 8 (early termination) The ratio of LDL-C/HDL-C was reported.
Change From Baseline in High Sensitivity C- Reactive Protein (hsCRP) at Week 1, 2, 3, 4, and 8 Baseline, Week 1, 2, 3, 4, 8 (early termination) 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.
Number of Participants Reporting Clinically Significant Change From Baseline in Epstein-Barr Virus (EBV) Values Baseline up to Week 8 (early termination) 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.
Number of Participants Reporting Clinically Significant Change From Baseline in Cytomegalovirus (CMV) Values Baseline up to Week 8 (early termination) 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.
Number of Participants Reporting Clinically Significant Change From Baseline in Herpes Simplex Virus Deoxyribonucleic Acid (HSV DNA) Values Baseline up to Week 8 (early termination) 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.
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 Baseline up to Week 8 (early termination) 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.
Trial Locations
- Locations (45)
Northwest Arkansas Clinical Trials Center, PLLC/Hull Dermatology, PA
🇺🇸Rogers, Arkansas, United States
California Dermatology & Clinical Research Institute
🇺🇸Encinitas, California, United States
Clinical Science Institute
🇺🇸Santa Monica, California, United States
Dermatology Specialists, Inc.
🇺🇸Oceanside, California, United States
Olympian Clinical Research
🇺🇸Clearwater, Florida, United States
Westcoast Radiology Services
🇺🇸Clearwater, Florida, United States
North Florida Dermatology Associates, PA
🇺🇸Jacksonville, Florida, United States
Park Avenue Dermatology, PA
🇺🇸Orange Park, Florida, United States
Advanced Medical Research, Inc
🇺🇸Atlanta, Georgia, United States
Leavitt Medical Associates of Florida d/b/a Ameriderm Research
🇺🇸Ormond Beach, Florida, United States
Columbus Regional Research Institute
🇺🇸Columbus, Georgia, United States
DS Research
🇺🇸Louisville, Kentucky, United States
Dartmouth-Hitchcock Medical Center - Section of Dermatology
🇺🇸Lebanon, New Hampshire, United States
Clinical Pharmacology Study Group
🇺🇸Worcester, Massachusetts, United States
Shondra L Smith, MD
🇺🇸Lake Charles, Louisiana, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
Dermatology Consulting Services
🇺🇸High Point, North Carolina, United States
Clinical Partners, LLC
🇺🇸Johnston, Rhode Island, United States
Total Skin and Beauty Dermatology Center, PC
🇺🇸Birmingham, Alabama, United States
International Dermatology Research, Inc.
🇺🇸Miami, Florida, United States
Dawes Fretzin Clinical Research Group, LLC
🇺🇸Indianapolis, Indiana, United States
Dawes Fretzin Dermatology Group, LLC
🇺🇸Indianapolis, Indiana, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Duke University Medical Center - Shipment Only
🇺🇸Durham, North Carolina, United States
Lynn Health Science Institute
🇺🇸Oklahoma City, Oklahoma, United States
Huntington Medical Foundation/Specialty Office
🇺🇸Pasadena, California, United States
Lynderm Research Inc.
🇨🇦Markham, Ontario, Canada
SKiN Centre for Dermatology
🇨🇦Peterborough, Ontario, Canada
Dundee Dermatology
🇺🇸West Dundee, Illinois, United States
Dermatology Research Associates
🇺🇸Los Angeles, California, United States
Enverus Medical Research
🇨🇦Surrey, British Columbia, Canada
Innovaderm Research Inc.
🇨🇦Montreal, Quebec, Canada
Dermatology Treatment & Research Center, PA
🇺🇸Dallas, Texas, United States
Co-Medica Research Network Inc.
🇨🇦Courtice, Ontario, Canada
Health Concepts
🇺🇸Rapid City, South Dakota, United States
The Centre for Dermatology & Cosmetic
🇨🇦Richmond Hill, Ontario, Canada
Dr Isabelle Delorme Inc.
🇨🇦Drummondville, Quebec, Canada
Q & T Research Sherbrooke Inc.
🇨🇦Sherbrooke, Quebec, Canada
Arlington Research Center, Inc.
🇺🇸Arlington, Texas, United States
Center for Clinical Studies
🇺🇸Houston, Texas, United States
Research by ICLS
🇨🇦Oakville, Ontario, Canada
K.Papp Clinical Research Inc.
🇨🇦Waterloo, Ontario, Canada
Virginia Clinical Research
🇺🇸Norfolk, Virginia, United States
Premier Clinical Research
🇺🇸Spokane, Washington, United States
Columbus Dermatology, P.C.
🇺🇸Columbus, Georgia, United States