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

• ClinicalTrials.gov Identifier: NCT02969018
• Recruitment Status: Completed
• First Posted: November 21, 2016
• Results First Posted: March 29, 2019
• Last Update Posted: March 29, 2019
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: November 17, 2016
• First Posted Date: November 21, 2016
• Results First Submitted Date: February 13, 2019
• Results First Posted Date: March 29, 2019
• Last Update Posted Date: March 29, 2019
• Actual Study Start Date: December 2016
• Actual Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 28, 2019)

Change From Baseline in Psoriasis Area and Severity Index (PASI) Score at Week 12 [ Time Frame: Baseline (Day 1 pre-dose), 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.

• Original Primary Outcome Measures (submitted: November 17, 2016): Change from baseline in Psoriasis Area Severity Index (PASI) score at Week 12 [ Time Frame: Baseline, Week 12 ]

Current Secondary Outcome Measures (submitted: March 28, 2019)

• Percentage of Participants Achieving a Psoriasis Area and Severity Index 75 (PASI75) Response at Week 12 [ Time Frame: 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.
• Change From Baseline in PASI Scores at Week 4 by Induction Dose [ Time Frame: Baseline (Day 1 pre-dose), Week 4 ]
  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.
• Percentage of Participants Achieving PASI75 Responses at Weeks 1, 2, 4, 6, 8, 10, 14, 16 [ Time Frame: 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.
• Percentage of Participants Achieving a Psoriasis Area and Severity Index 50 (PASI50) Response at Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 [ Time Frame: 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.
• Percentage of Participants Achieving a Psoriasis Area and Severity Index 90 (PASI90) Response at Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 [ Time Frame: 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.
• Change From Baseline in PASI Scores at Weeks 1, 2, 4, 6, 8, 10, 14, 16 [ Time Frame: Baseline (Day 1 pre-dose), 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.
• Percent Change From Baseline in PASI Scores at Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 [ Time Frame: Baseline (Day 1 pre-dose), 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.
• Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From first dose of study treatment (Day 1) up to Week 20 ]
  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.
• Number of Participants Who Discontinued From the Study Due to Treatment-Emergent AEs [ Time Frame: From first dose of study treatment (Day 1) up to Week 20 ]
  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).
• Change From Baseline in Blood Lipid Level at Weeks 4 and 12 [ Time Frame: Baseline (Day 1 pre-dose), Weeks 4 and 12 ]
  Lipid panel included low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, total cholesterol, and triglycerides.
• Number of Participants With Any Post-Baseline Laboratory Test Abnormalities [ Time Frame: From first dose of study treatment (Day 1) up to Week 16 ]
  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).
• Number of Participants With Post-Baseline Vital Sign Abnormalities [ Time Frame: From first dose of study treatment (Day 1) up to Week 16 ]
  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.
• Number of Participants With Post-Baseline Electrocardiogram (ECG) Abnormalities [ Time Frame: From first dose of study treatment (Day 1) up to Week 16 ]
  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.

Original Secondary Outcome Measures (submitted: November 17, 2016)

• Proportion of subjects achieving PASI 75 response at Week 12 [ Time Frame: Week 12 ]
• Proportion of subjects achieving 50%, 75% and 90% reduction from baseline PASI [ Time Frame: Weeks 1 through 16 ]
• Change from baseline in PASI scores [ Time Frame: Baseline, Weeks 1 through 16 ]
• Change from baseline in PASI score at Week 4 [ Time Frame: Baseline, Week 4 ]
• Change from baseline in clinical chemistry laboratory parameters [ Time Frame: Baseline, Weeks 1 through 16 ]
• Change from baseline in vital signs [ Time Frame: Baseline, Weeks 1 through 12 ]
• Change from baseline in ECG parameters [ Time Frame: Baseline, Week 4, Week 12 ]
• Change from baseline in blood lipid level [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16 ]
  Lipid panel includes: total cholesterol, triglycerides, HDL, LDL
• Change from baseline in clinical hematological laboratory parameters [ Time Frame: Baseline, Weeks 1 through 16 ]
• Percent change from baseline in PASI scores [ Time Frame: Baseline, Weeks 1 through 16 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study To Evaluate Safety And Efficacy Of PF-06700841 In Subjects With Moderate To Severe 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
• Brief Summary: The purpose of this study is to determine whether PF-06700841 is safe and effective in the treatment of chronic plaque psoriasis.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Chronic Plaque Psoriasis

Intervention

• Drug: PF-06700841
• Other: Placebo

Study Arms

• 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
  Intervention: 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
  Intervention: 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
  Intervention: 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
  Intervention: 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
  Intervention: 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
  Intervention: 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
  Intervention: Drug: PF-06700841
• Placebo Comparator: Placebo
  12 weeks once daily placebo
  Intervention: Other: Placebo

Publications *

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 2, 2018): 212
• Original Estimated Enrollment (submitted: November 17, 2016): 200
• Actual Study Completion Date: March 2018
• Actual Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Poland, United States

Administrative Information

• NCT Number: NCT02969018
• Other Study ID Numbers: B7931004; 2016-004049-96 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: March 2019