Dose Ranging Study To Assess Efficacy, Safety and Tolerability Of PF-06700841 Topical Cream In Psoriasis

Psoriasis Clinical Trial

Official title:

A PHASE 2B, RANDOMIZED, DOUBLE BLIND, VEHICLE CONTROLLED, PARALLEL-GROUP, DOSE RANGING STUDY TO ASSESS EFFICACY, SAFETY, TOLERABILITY AND PHARMACOKINETICS OF PF-06700841 TOPICAL CREAM APPLIED ONCE OR TWICE DAILY FOR 12 WEEKS IN PARTICIPANTS WITH MILD TO MODERATE CHRONIC PLAQUE PSORIASIS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03850483
• Other study ID #: B7931023
• Secondary ID: 2018-003051-38
• Status: Completed
• Phase: Phase 2
• Start date: April 8, 2019
• Est. completion date: April 20, 2021

Study information

• Verified date: June 2022
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 2b, randomized, double blind, vehicle controlled, parallel group, multicenter study in participants with mild to moderate plaque psoriasis. The duration of study participation will be approximately 22 weeks, including up to a 6 week screening period, 12 week treatment period, and approximately 4 week follow up period. Approximately 280 participants are planned to be randomized into the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 344
• Est. completion date: April 20, 2021
• Est. primary completion date: April 20, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• plaque psoriasis for 6 months

• PGA score mild or moderate

• body surface area (BSA) 2-15%

Exclusion Criteria:

• other skin conditions that would interfere with the evaluation of psoriasis

• history of herpes zoster or simplex

• Infected with Mycobacterium tuberculosis

Related Conditions & MeSH terms

• Psoriasis

Intervention

Drug:
• PF-06700841
PF-06700841 topical cream
• Vehicle (Placebo)
Vehicle topical cream

Locations

Country	Name	City	State
Australia	Emeritus Research	Camberwell	Victoria
Australia	Sinclair Dermatology	East Melbourne	Victoria
Australia	Cabrini Hospital	Malvern	Victoria
Australia	Veracity Clinical Research Pty Ltd	Woolloongabba	Queensland
Bulgaria	Center for Skin and Venereal Diseases EOOD - Sofia	Sofia
Bulgaria	DCC Alexandrovska	Sofia
Bulgaria	Dermatological Clinic Sofia	Sofia
Bulgaria	Diagnostic Consultative Center - Fokus-5 - Medical Establishment for Outpatient Care OOD	Sofia
Canada	SKiN Health	Cobourg	Ontario
Canada	Innovaderm Research Inc.	Montreal	Quebec
Canada	Diex Recherche Sherbrooke Inc.	Sherbrooke	Quebec
Canada	Wiseman Dermatology Research Inc.	Winnipeg	Manitoba
Denmark	Gentofte Hospital	Hellerup
Germany	Fachklinik Bad Bentheim	Bad Bentheim
Germany	Emovis GmbH	Berlin
Germany	ISA - Interdisciplinary Study Association GmbH	Berlin
Germany	Rothhaar Studien GmbH	Berlin
Germany	Klinikum Bielefeld gem.GmbH	Bielefeld
Germany	Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden	Dresden
Germany	MENSINGDERMA research GmbH	Hamburg
Germany	MVZ Alstermed GmbH	Hamburg
Germany	Dermatologische Gemeinschaftspraxis	Mahlow
Germany	Klinische Forschung Schwerin GmbH	Schwerin
Hungary	Semmelweis Egyetem Altalanos Orvostudomanyi Kar	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen
Hungary	Bacs-Kiskun Megyei Korhaz Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar Oktato Korhaza	Kecskemet
Hungary	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont	Szeged
Japan	Nakatsuhifuka Clinic	Kita-ku, Osaka-shi	Osaka
Japan	Parkside Hiroo Ladies Clinic	Minato-ku	Tokyo
Japan	Tanpopo Skin Clinic	Ota Ku	Tokyo
Japan	Kitago Dermatology Clinic	Sapporo-shi	Hokkaido
Japan	Samoncho Dermatological Clinic	Shinjuku-ku	Tokyo
Japan	Medical Corporation Jitai-kai Tachikawa Dermatology Clinic	Tachikawa	Tokyo
Latvia	Aesthetic dermatology clinic of Prof. J. Kisis	Riga
Latvia	Health and Aesthetics Ltd	Riga
Latvia	Riga 1st Hospital	Riga
Latvia	Outpatient Clinic of Ventspils	Ventspils
Poland	Zdrowie Osteo-Medic s.c. LiA Racewicz, AiJ Supronik	Bialystok
Poland	Nasz Lekarz Przychodnie Medyczne	Torun
Poland	MTZ Clinical Research Sp. z o.o	Warszawa
Poland	WroMedica I. Bielicka, A. Strzalkowska s.c.	Wroclaw
United States	Anaheim Clinical Trials, LLC	Anaheim	California
United States	California Skin Institute	Anaheim	California
United States	Austin Institute for Clinical Research, Inc.	Austin	Texas
United States	Meridian Clinical Research, LLC	Baton Rouge	Louisiana
United States	Bayside Dermatology Center	Bayside	New York
United States	Hassman Research Institute	Berlin	New Jersey
United States	New England Research Associates, LLC	Bridgeport	Connecticut
United States	Ds Research	Clarksville	Indiana
United States	Olympian Clinical Research	Clearwater	Florida
United States	studies in Dermatology, LLC	Cypress	Texas
United States	Accel Research Sites - DeLand Clinical Research Unit	DeLand	Florida
United States	Psoriasis Treatment Center of Central New Jersey	East Windsor	New Jersey
United States	California Dermatology & Clinical Research Institute	Encinitas	California
United States	First OC Dermatology	Fountain Valley	California
United States	Summit Clinical Research, LLC	Franklin	Virginia
United States	Rivergate Dermatology Clinical Research	Goodlettsville	Tennessee
United States	Dermatology Consulting Services, PLLC	High Point	North Carolina
United States	Burke Pharmaceutical Research	Hot Springs	Arkansas
United States	Center for Clinical Studies, LTD. LLP	Houston	Texas
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	DS Research	Louisville	Kentucky
United States	Virginia Dermatology and Skin Cancer Center	Norfolk	Virginia
United States	MidState Skin Institute	Ocala	Florida
United States	Renstar Medical Research	Ocala	Florida
United States	Renstar Medical Research	Ocala	Florida
United States	Park Avenue Dermatology, PA	Orange Park	Florida
United States	M3 Wake Research, Inc.	Raleigh	North Carolina
United States	Health Concepts	Rapid City	South Dakota
United States	MediSearch Clinical Trials	Saint Joseph	Missouri
United States	Texas Dermatology and Laser Specialists	San Antonio	Texas
United States	Clinical Science Institute	Santa Monica	California
United States	Center for Dermatology and Plastic Surgery	Scottsdale	Arizona
United States	Center for Dermatology and Plastic Surgery/CCT	Scottsdale	Arizona
United States	Dermatology Physicians of Connecticut	Shelton	Connecticut
United States	Center for Clinical Studies	Tampa	Florida
United States	Vital Prospects Clinical Research Institute, PC	Tulsa	Oklahoma
United States	Center for Clinical Studies	Webster	Texas
United States	Dundee Dermatology	West Dundee	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  Denmark,  Germany,  Hungary,  Japan,  Latvia,  Poland, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Psoriasis Area and Severity Index (PASI) Score at Week 12	The Psoriasis Area and Severity Index (PASI) score (0-72, with higher score representing greater severity) is a measurement of the severity and extent of psoriasis. The four regions of the body parts are head (10%), arms (20%), trunk (30%) and legs (40%). In each region, the area is expressed as a score of 0 (nothing), 1 (1-9%), 2 (10-29%), 3 (30-49%), 4 (50-69%), 5 (70-89%) or 6 (90-100%). Within each area, the degree of severity for erythema, induration and scaling are estimated between 0 and 4, with 4 being the highest severity. The final score combines disease severity and effected body surface area (BSA) from for four regions using the formula PASI =0.1Ah(Eh + Ih + Sh) + 0.2Au(Eu + Iu + Su) + 0.3At(Et + It + St) + 0.4Al(El + Il + Sl) where A = Area Score; E = erythema; I =induration; S = scaling; h = head; u = upper limbs; t = trunk; l = lower limbs.	Baseline, Week 12
Secondary	Percentage of Participants With Physician Global Assessment (PGA) Score Clear (0) or Almost Clear (1) and Greater Than or Equal to (>=) 2 Points Improvement From Baseline at Week 12	PGA of psoriasis was scored on a 5-point scale, reflecting a global consideration of the erythema, induration, and scaling across all psoriatic lesions. Average erythema, induration, and scaling were scored separately over the whole body according to a 5-point severity scale (0 [no symptom] to 4 [severe symptom]). The total score was calculated as average of the 3 severity scores and rounded to the nearest whole number score to determine the PGA score and category. Scale for PGA: 0= clear, 1= almost clear, 2= mild, 3= moderate and 4= severe. Higher scores indicate more severity.	Baseline, Week 12
Secondary	Percentage of Participants With 75% Reduction From Baseline in PASI at Week 1, 2, 4, 6, 8, 10, 12, 14, and 16	The PASI score (0-72, with higher score representing greater severity) is a measurement of the severity and extent of psoriasis. The four regions of the body parts are head (10%), arms (20%), trunk (30%) and legs (40%). In each region, the area is expressed as a score of 0 (nothing), 1 (1-9%), 2 (10-29%), 3 (30-49%), 4 (50-69%), 5 (70-89%) or 6 (90-100%). Within each area, the degree of severity for erythema, induration and scaling are estimated between 0 and 4, with 4 being the highest severity. The final score combines disease severity and effected BSA from for four regions using the formula PASI =0.1Ah(Eh + Ih + Sh) + 0.2Au(Eu + Iu + Su) + 0.3At(Et + It + St) + 0.4Al(El + Il + Sl) where A = Area Score; E = erythema; I =induration; S = scaling; h = head; u = upper limbs; t = trunk; l = lower limbs.	Baseline, Week 1, 2, 4, 6, 8, 10, 12, 14, and 16
Secondary	Change From Baseline in PASI Scores at Week 1, 2, 4, 6, 8, 10 and 12	The PASI score (0-72, with higher score representing greater severity) is a measurement of the severity and extent of psoriasis. The four regions of the body parts are head (10%), arms (20%), trunk (30%) and legs (40%). In each region, the area is expressed as a score of 0 (nothing), 1 (1-9%), 2 (10-29%), 3 (30-49%), 4 (50-69%), 5 (70-89%) or 6 (90-100%). Within each area, the degree of severity for erythema, induration and scaling are estimated between 0 and 4, with 4 being the highest severity. The final score combines disease severity and effected BSA from for four regions using the formula PASI =0.1Ah(Eh + Ih + Sh) + 0.2Au(Eu + Iu + Su) + 0.3At(Et + It + St) + 0.4Al(El + Il + Sl) where A = Area Score; E = erythema; I =induration; S = scaling; h = head; u = upper limbs; t = trunk; l = lower limbs.	Baseline, Week 1, 2, 4, 6, 8, 10 and 12
Secondary	Change From Baseline in PASI Scores at Week 14 and 16	The PASI score (0-72, with higher score representing greater severity) is a measurement of the severity and extent of psoriasis. The four regions of the body parts are head (10%), arms (20%), trunk (30%) and legs (40%). In each region, the area is expressed as a score of 0 (nothing), 1 (1-9%), 2 (10-29%), 3 (30-49%), 4 (50-69%), 5 (70-89%) or 6 (90-100%). Within each area, the degree of severity for erythema, induration and scaling are estimated between 0 and 4, with 4 being the highest severity. The final score combines disease severity and effected BSA from for four regions using the formula PASI =0.1Ah(Eh + Ih + Sh) + 0.2Au(Eu + Iu + Su) + 0.3At(Et + It + St) + 0.4Al(El + Il + Sl) where A = Area Score; E = erythema; I =induration; S = scaling; h = head; u = upper limbs; t = trunk; l = lower limbs.	Baseline, Week 14 and 16
Secondary	Percent Change From Baseline in PASI Scores at Week 1, 2, 4, 6, 8, 10 and 12	The PASI score (0-72, with higher score representing greater severity) is a measurement of the severity and extent of psoriasis. The four regions of the body parts are head (10%), arms (20%), trunk (30%) and legs (40%). In each region, the area is expressed as a score of 0 (nothing), 1 (1-9%), 2 (10-29%), 3 (30-49%), 4 (50-69%), 5 (70-89%) or 6 (90-100%). Within each area, the degree of severity for erythema, induration and scaling are estimated between 0 and 4, with 4 being the highest severity. The final score combines disease severity and effected BSA from for four regions using the formula PASI =0.1Ah(Eh + Ih + Sh) + 0.2Au(Eu + Iu + Su) + 0.3At(Et + It + St) + 0.4Al(El + Il + Sl) where A = Area Score; E = erythema; I =induration; S = scaling; h = head; u = upper limbs; t = trunk; l = lower limbs.	Baseline, Week 1, 2, 4, 6, 8, 10 and 12
Secondary	Percent Change From Baseline in PASI Scores at Week 14 and 16	The PASI score (0-72, with higher score representing greater severity) is a measurement of the severity and extent of psoriasis. The four regions of the body parts are head (10%), arms (20%), trunk (30%) and legs (40%). In each region, the area is expressed as a score of 0 (nothing), 1 (1-9%), 2 (10-29%), 3 (30-49%), 4 (50-69%), 5 (70-89%) or 6 (90-100%). Within each area, the degree of severity for erythema, induration and scaling are estimated between 0 and 4, with 4 being the highest severity. The final score combines disease severity and effected BSA from for four regions using the formula PASI =0.1Ah(Eh + Ih + Sh) + 0.2Au(Eu + Iu + Su) + 0.3At(Et + It + St) + 0.4Al(El + Il + Sl) where A = Area Score; E = erythema; I =induration; S = scaling; h = head; u = upper limbs; t = trunk; l = lower limbs.	Baseline, Week 14 and 16
Secondary	Absolute Peak-Pruritus Numerical Rating Scale (PP-NRS) Score at Baseline, Week 1, 2, 4, 6, 8, 10 and 12	Participants were asked to assess their itch intensity over the past 24 hours, on a scale from 0 (no itching) to 10 (worst possible itching). Higher scores indicated worse itch.	Baseline, Week 1, 2, 4, 6, 8, 10 and 12
Secondary	Absolute PP-NRS Score at Week 14 and 16	Participants were asked to assess their itch intensity over the past 24 hours, on a scale from 0 (no itching) to 10 (worst possible itching). Higher scores indicated worse itch.	Week 14 and 16
Secondary	Change From Baseline in PP-NRS Score at Week 1, 2, 4, 6, 8, 10 and 12	Participants were asked to assess their itch intensity over the past 24 hours, on a scale from 0 (no itching) to 10 (worst possible itching). Higher scores indicated worse itch.	Baseline, Week 1, 2, 4, 6, 8, 10 and 12
Secondary	Change From Baseline in PP-NRS Score at Week 14 and 16	Participants were asked to assess their itch intensity over the past 24 hours, on a scale from 0 (no itching) to 10 (worst possible itching). Higher scores indicated worse itch.	Baseline, Week 14 and 16
Secondary	Absolute Psoriasis Symptom Inventory (PSI) Score at Baseline, Week 1, 2, 4, 6, 8, 10, 12, 14 and 16, Early Termination (ET), ET Follow-up Visit 1 and 2	PSI was a self-administered 8-item questionnaire that measured the severity of psoriasis symptoms over the past 24 hours and the past 7 days. PSI included following 8 items: itch, pain, burning, stinging, cracking, scaling, flaking, and redness. Each item was rated on a scale from 0 to 4, where 0= not at all severe, 1= mild, 2= moderate, 3= severe and 4= very severe. Scores from all items were summed to give PSI score range from 0 (no severity) to 32 (maximum severity), higher PSI score indicated greater severity.	Baseline, Week 1, 2, 4, 6, 8, 10, 12, 14 and 16, ET (Prior to Week 12), ET Follow-up Visit 1 (2 weeks post ET) and 2 (4 weeks post ET)
Secondary	Change From Baseline in PSI Score at Week 1, 2, 4, 6, 8, 10, 12, 14 and 16, ET, ET Follow-up Visit 1 and 2	PSI was a self-administered 8-item questionnaire that measured the severity of psoriasis symptoms over the past 24 hours and the past 7 days. PSI included following 8 items: itch, pain, burning, stinging, cracking, scaling, flaking, and redness. Each item was rated on a scale from 0 to 4, where 0= not at all severe, 1= mild, 2= moderate, 3= severe and 4= very severe. Scores from all items were summed to give PSI score range from 0 (no severity) to 32 (maximum severity), higher PSI score indicated greater severity.	Baseline, Week 1, 2, 4, 6, 8, 10, 12, 14 and 16, ET (Prior to Week 12), ET Follow-up Visit 1 (2 weeks post ET) and 2 (4 weeks post ET)
Secondary	Percentage of Participants With PGA Score Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Week 1, 2, 4, 6, 8, 10, 14, and 16	PGA of psoriasis was scored on a 5-point scale, reflecting a global consideration of the erythema, induration, and scaling across all psoriatic lesions. Average erythema, induration, and scaling were scored separately over the whole body according to a 5-point severity scale (0 [no symptom] to 4 [severe symptom]). The total score was calculated as average of the 3 severity scores and rounded to the nearest whole number score to determine the PGA score and category. Scale for PGA: 0= clear, 1= almost clear, 2= mild, 3= moderate and 4= severe. Higher scores indicate more severity.	Baseline, Week 1, 2, 4, 6, 8, 10, 14, and 16
Secondary	Percentage of Participants Who Achieved PSI Score of 0 (Not at All) or 1 (Mild) on All Items at Week 1, 2, 4, 6, 8, 10, 12, 14, and 16	PSI was a self-administered 8-item questionnaire that measured the severity of psoriasis symptoms over the past 24 hours and the past 7 days. PSI included following 8 items: itch, pain, burning, stinging, cracking, scaling, flaking, and redness. Each item was rated on a scale from 0 to 4, where 0= not at all severe, 1= mild, 2= moderate, 3= severe and 4= very severe. Scores from all items were summed to give PSI score range from 0 (no severity) to 32 (maximum severity), higher PSI score indicated greater severity.	Week 1, 2, 4, 6, 8, 10, 12, 14, and 16
Secondary	Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment Related AEs and SAEs	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and all non-SAEs. Treatment emergent AEs (TEAEs) were events that occurred between first dose of study drug and up to 4 weeks after last dose that were absent before treatment or that worsened relative to pretreatment state. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator.	Day 1 of study drug dose to maximum of 4 weeks post last dose (maximum up to 16 weeks)
Secondary	Number of Participants With TEAEs by Severity	An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. AE was assessed according to severity; mild (not causing any significant problem, dose adjustment not required), moderate (caused problem that does not interfere significantly with usual activities or the clinical status, dose adjustment needed due to adverse event) and severe (caused problem that interfered significantly with usual activities or the clinical status, study drug stopped due to adverse event).	Day 1 of study drug dose to maximum of 4 weeks post last dose (maximum up to 16 weeks)
Secondary	Number of Participants Who Discontinued From Study Due to Adverse Events	An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship.	Day 1 of study drug dose to maximum of 4 weeks post last dose (maximum up to 16 weeks)
Secondary	Number of Participants With Laboratory Abnormalities Meeting Specified Criteria	Bilirubin: greater than (>) 1.5* upper limit normal (ULN); aspartate aminotransferase, alanine aminotransferase: >2.5*ULN; creatinine, cystatin C: >1.3*ULN; creatine kinase: >2.0*ULN; glomerular filtration rate (GFR) CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) Equat: less than (<) 60 milliliter (mL)/minute (min)/1.73 meter(m)^2, greater than or equal to (>=) 30% decrease from baseline; GFR: <60 mL/min/1.73m^2.	Day 1 of study drug dose to maximum of 4 weeks post last dose (maximum up to 16 weeks)
Secondary	Number of Participants With Categorical Summary of Post-Baseline Electrocardiogram (ECG) Data	Following were ECG criteria used for categorical summary:1) PR interval: percentage change >=25/50%, QRS interval: value >140 msec, and QT interval corrected using the Fridericia's formula (QTcF): 450 msec < value less than equal to (<=) 480 and 30 < change <=60.	Post-baseline to Week 6, Post-baseline to Week 12
Secondary	Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data	Following were the vital signs criteria: 1) Pulse rate: value <40 beats per min (bpm), value >120 bpm; 2) Sitting diastolic blood pressure (DBP): value <50 mmHg; change >=20 mmHg increase; change >=20 mmHg decrease; 3) Sitting systolic blood pressure (SBP): value <90 mmHg, change >=30 mmHg increase, change >=30 mmHg decrease; 4) Supine DBP: value <50 mmHg, change >=20 mmHg increase, change >=20 mmHg decrease; 5) Supine SBP: value <90 mmHg, change >=30 mmHg increase, change >=30 mmHg decrease.	Post-baseline to Week 12
Secondary	Number of Participants Classified Per Skin Tolerability Assessment Severity Grades on Day 1, Week 1, 2, 4, 6, 8, 10, 12, 14, 16	At the site of study drug application, skin tolerability was assessed for non-lesional skin surrounding the plaques on a scale from 0 to 4. Grade 0= none (no evidence of local intolerance), Grade 1= mild (minimal erythema and/or edema, slight glazed appearance), Grade 2= moderate (definite erythema and/or oedema with peeling and/or cracking but needs no adaptation of posology), Grade 3= severe, reported as AE (erythema, oedema glazing with fissures, few vesicles or papules: consider removing topical agent [if still in place]), Grade 4= very severe, reported as AE (strong reaction spreading beyond the treated area, bullous reaction, erosions: removal of topical agent [if still in place]).	Day 1, Week 1, 2, 4, 6, 8, 10, 12, 14, 16

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