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

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

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

Study Overview

• Status: Completed
• Conditions: Chronic Plaque Psoriasis
• Intervention / Treatment: Other: Placebo; Drug: PF-06700841

• Study Type: Interventional
• Enrollment (Actual): 212
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V4X7
    • Centre de Recherche Dermatologique du Quebec metropolitain (CRDQ)
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3M 3Z4
      • Wiseman Dermatology Research Inc.
  • Ontario
    • Markham, Ontario, Canada, L3P 1X2
      • Lynderm Research Inc
    • Oakville, Ontario, Canada, L6J 7W5
      • Research by ICLS
    • Peterborough, Ontario, Canada, K9J 5K2
      • SKiN Centre for Dermatology
    • Richmond Hill, Ontario, Canada, L4B 1A5
      • The Centre for Dermatology
    • Waterloo, Ontario, Canada, N2J 1C4
      • K.Papp Clinical Research Inc.
  • Quebec
    • Sherbrooke, Quebec, Canada, J1L 0H8
      • Diex Research Sherbrooke Inc.
• Poland
  • Gdansk, Poland, 80-546
    • Centrum Badan Klinicznych PI-House sp. z o.o.
  • Gdansk, Poland, 80-266
    • Centrum Medyczne Enel-Med Przychodnia Grunwaldzka
  • Lodz, Poland, 90-436
    • Dermoklinika Centrum Medyczne s.c. M.Kierstan, J. Narbutt, A. Lesiak
  • Torun, Poland, 87-100
    • NZOZ "Nasz Lekarz" - Praktyka Grupowa Lekarzy Rodzinnych z Przychodnia Specjalistyczna
  • Warszawa, Poland, 02-106
    • MTZ Clinical Research Sp. z o.o.
  • Wroclaw, Poland, 51-685
    • Wromedica s.c.
• United States
  • Arkansas
    • Rogers, Arkansas, United States, 72758
      • Northwest Arkansas Clinical Trials Center, PLLC/Hull Dermatology, PA
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC
    • Encinitas, California, United States, 92024
      • California Dermatology & Clinical Research Institute
    • Sacramento, California, United States, 95819
      • Emil A. Tanghetti, MD dba Center for Dermatology and Laser Surgery
    • Santa Ana, California, United States, 92701
      • Southern California Dermatology
    • Santa Monica, California, United States, 90404
      • Clinical Science Institute
    • Santa Monica, California, United States, 90403
      • Tower Saint John's Imaging
  • Florida
    • Orange Park, Florida, United States, 32073
      • Park Avenue Dermatology
    • Orange Park, Florida, United States, 32073
      • Park Avenue Dermatology Administrative Annex
    • Tampa, Florida, United States, 33609
      • Olympian Clinical Research
    • Tampa, Florida, United States, 33624
      • Forward Clinical Trials, Inc
    • Tampa, Florida, United States, 33609
      • Rose Radiology
  • Illinois
    • West Dundee, Illinois, United States, 60118
      • Dundee Dermatology
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Dawes Fretzin Clinical Research Group, LLC
    • Indianapolis, Indiana, United States, 46256
      • Dawes Fretzin Dermatology Group, LLC
  • New Jersey
    • East Windsor, New Jersey, United States, 08520
      • Psoriasis Treatment Center of Central New Jersey
  • New York
    • New York, New York, United States, 10065
      • The Rockefeller University
    • Rochester, New York, United States, 14623
      • Skin Search of Rochester, Inc.
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27516
      • UNC Dermatology and Skin Cancer Center
    • Chapel Hill, North Carolina, United States, 27514
      • Investigational Drug Services, UNC Hospitals
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Clinical and Translation Research Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
    • Tulsa, Oklahoma, United States, 74136
      • Vital Prospects Clinical Research Institute, P.C
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Health Concepts
  • Texas
    • Houston, Texas, United States, 77004
      • Center for Clinical Studies
    • San Antonio, Texas, United States, 78213
      • Lee Medical Associates, PA
    • San Antonio, Texas, United States, 78213
      • Progressive Clinical Research, PA
    • San Antonio, Texas, United States, 78218
      • Texas Dermatology and Laser Specialists
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Clinical Research, Inc.
  • Washington
    • Spokane, Washington, United States, 99202
      • Premier Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: PF-06700841 60 mg followed by 30 mg once daily; 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
EXPERIMENTAL: PF-06700841 60 mg followed by 10 mg once daily; 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
EXPERIMENTAL: PF-06700841 60mg once daily followed by 100mg once weekly; 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
EXPERIMENTAL: PF-06700841 60mg once daily followed by placebo once daily; 4 week induction with 60 mg PF-06700841 once daily, followed by 8 week chronic administration of placebo once daily	Drug: PF-06700841
EXPERIMENTAL: PF-06700841 30mg once daily; 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
EXPERIMENTAL: PF-06700841 30mg once daily followed by 10mg once daily; 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
EXPERIMENTAL: PF-06700841 30mg once daily followed by 100mg once weekly; 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
PLACEBO_COMPARATOR: Placebo; 12 weeks once daily placebo	Other: Placebo

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Hughes JH, Qiu R, Banfield C, Dowty ME, Nicholas T. Population Pharmacokinetics of Oral Brepocitinib in Healthy Volunteers and Patients. Clin Pharmacol Drug Dev. 2022 Dec;11(12):1447-1456. doi: 10.1002/cpdd.1163. Epub 2022 Aug 31.
• Forman SB, Pariser DM, Poulin Y, Vincent MS, Gilbert SA, Kieras EM, Qiu R, Yu D, Papacharalambous J, Tehlirian C, Peeva E. TYK2/JAK1 Inhibitor PF-06700841 in Patients with Plaque Psoriasis: Phase IIa, Randomized, Double-Blind, Placebo-Controlled Trial. J Invest Dermatol. 2020 Dec;140(12):2359-2370.e5. doi: 10.1016/j.jid.2020.03.962. Epub 2020 Apr 18.
• Fensome A, Ambler CM, Arnold E, Banker ME, Brown MF, Chrencik J, Clark JD, Dowty ME, Efremov IV, Flick A, Gerstenberger BS, Gopalsamy A, Hayward MM, Hegen M, Hollingshead BD, Jussif J, Knafels JD, Limburg DC, Lin D, Lin TH, Pierce BS, Saiah E, Sharma R, Symanowicz PT, Telliez JB, Trujillo JI, Vajdos FF, Vincent F, Wan ZK, Xing L, Yang X, Yang X, Zhang L. Dual Inhibition of TYK2 and JAK1 for the Treatment of Autoimmune Diseases: Discovery of (( S)-2,2-Difluorocyclopropyl)((1 R,5 S)-3-(2-((1-methyl-1 H-pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone (PF-06700841). J Med Chem. 2018 Oct 11;61(19):8597-8612. doi: 10.1021/acs.jmedchem.8b00917. Epub 2018 Aug 16.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2016
• Primary Completion (ACTUAL): March 1, 2018
• Study Completion (ACTUAL): March 1, 2018

Study Registration Dates

• First Submitted: November 17, 2016
• First Submitted That Met QC Criteria: November 17, 2016
• First Posted (ESTIMATE): November 21, 2016

Study Record Updates

• Last Update Posted (ACTUAL): March 29, 2019
• Last Update Submitted That Met QC Criteria: March 28, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: plaque psoriasis
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; PF-06700841
• Other Study ID Numbers: B7931004; 2016-004049-96 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.