Safety, Tolerability And Efficacy Study Of Topical PF-06763809 In Subjects With Mild To Moderate Chronic Plaque Psoriasis

A PHASE 1, RANDOMIZED, DOUBLE-BLIND, VEHICLE AND ACTIVE COMPARATOR-CONTROLLED, PSORIASIS PLAQUE TEST STUDY TO ASSESS SAFETY, TOLERABILITY, AND PSORIATIC SKIN INFILTRATE THICKNESS FOLLOWING REPEATED, TOPICAL DOSES OF PF-06763809 SOLUTION IN SUBJECTS WITH MILD TO MODERATE CHRONIC PLAQUE PSORIASIS

The study is a randomized, double blinded, vehicle and active comparator controlled, multiple dose study in subjects with chronic plaque psoriasis. The study will have approximately 15 completers. Each subjects will receive three different topical doses of PF 06763809, PF 06763809 vehicle, and two active comparators. These will be applied to six different treatment fields for 18 days. The total duration of participation in the study will be approximately 7 weeks (minimum) to approximately 11 weeks (maximum), including the interval from Screening to the Follow up phone call visit.

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: Drug: PF-06763809; Other: Vehicle; Drug: Calcipotriene/calcipotriol; Drug: Betamethasone

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10783
    • Rothaar Studien GmbH
  • Hamburg, Germany, 20095
    • Bioskin GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Psoriasis vulgaris in a chronic stable phase and with a plaque area of mild to moderate severity sufficient for six treatment fields located in up to three plaque areas
• Target lesion(s) should be on the trunk or extremities (excluding palms/soles).

Exclusion Criteria:

• History of skin sensitivity to topical prescription or non prescription products such as creams, lotions and cosmetics
• Psoriasis guttata, psoriasis punctata, psoriasis erythrodermatica, and pustular psoriasis
• Treatment with any biologics within 3 months prior to Day 1 of the study and during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: All subjects; All subjects will receive all six interventions/treatments applied to six different treatment fields.	Drug: PF-06763809; Three different concentrations will be administered to three different treatment fields: 2.3%, 0.8% and 0.23%; Other: Vehicle; Vehicle matching PF-06763809.; Drug: Calcipotriene/calcipotriol; Calcipotriene/calcipotriol 50 ug/mL solution; Drug: Betamethasone; Betamethasone 1 mg/g solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Psoriatic Skin Infiltrate Thickness	Baseline was defined to be the measurement on Day 1. MMRM analysis of changes in psoriatic skin in psoriatic skin infiltrate thickness/echo poor band (EPB) in response to PF-06763809 2.3%, 0.8% and 0.23% applied topically for 18 consecutive days as compared to the vehicle control. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.	Baseline, Days 7, 13 and 19
Number of Participants With Treatment-emergent Adverse Events (AEs)	Baseline was defined to be the measurement on Day 1. An AE was any untoward medical occurrence in a clinical investigation patient administered a product or medical device. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of investigational product.	Day 1 to Day 49
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)	Baseline was defined to be the measurement on Day 1. The safety laboratory tests including Hematology, Clinical Chemistry and Urinalysis were performed. Hematology evaluation included: hemoglobin (HGB) (gram per decilitre=g/dL), hematocrit, erythrocytes (Ery.), Ery. Mean Corpuscular Volume, Ery. Mean Corpuscular Hemoglobin, Ery. Mean Corpuscular HGB Concentration (picograms per cell=pg/cell), platelets, leukocytes, lymphocytes, and neutrophils. Clinical chemistry evaluation included: bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, protein, albumin, urea nitrogen, urea, creatinine, urate, sodium, potassium, chloride, calcium, bicarbonate, creatine kinase, and glucose. Urinalysis evaluation included: pH, urine glucose, ketones, urine protein, urine hemoglobin, urobilinogen, urine bilirubin, nitrite, and leukocyte esterase. LLN=lower limit of normal, ULN=upper limit of normal.	Day 1 to Day 49
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria	Baseline was defined to be the measurement on Day 1. ECG categorical summarization criteria: 1) PR interval (Value>=300 milliseconds [msec], %Change [Chg]>=25/50%); 2) QRS interval (Value>=140 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. The corrected QT interval by Fredericia=QTcF Interval.	Day 1 to Day 49
Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria	Baseline was defined to be the measurement on Day 1. Vital Signs including diastolic blood pressure (DBP), pulse rate, and systolic blood pressure (SBP) were measured.	Day 1 to Day 49

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve of the Psoriatic Skin Infiltrate Thickness	Baseline was defined to be the measurement on Day 1. To evaluate the Area Under the Curve (AUC) of psoriatic skin infiltrate thickness/EPB for PF 06763809 compared to vehicle by mixed model analysis. The AUC of the psoriatic skin infiltrate thickness/EPB from Day 1 to Day 19 was determined using the linear trapezoidal rule. The log AUC was performed by the natural logarithm of the AUC of the psoriatic skin infiltrate thickness/EPB. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.	Day 1 to Day 19
Change From Baseline in Skin Infiltrate Thickness in Response to PF-06763809 Compared to Calcipotriene/Calcipotriol Solution.	The effect of PF-06763809 compared to calcipotriene/calcipotriol solution in the change of psoriatic skin infiltrate thickness/EPB both within and following 18 days of treatment. Baseline was defined to be the measurement on Day 1. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.	Baseline, Days 7, 13 and 19
Change From Baseline in Skin Infiltrate Thickness in Response to PF-06763809 Compared to Betamethasone Solution.	The effect of PF-06763809 compared to betamethasone solution in the change of psoriatic skin infiltrate thickness/EPB both within and following 18 days of treatment. Baseline was defined to be the measurement on Day 1. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.	Baseline, Days 7, 13 and 19

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Berstein G, Zhang Y, Berger Z, Kieras E, Li G, Samuel A, Yeoh T, Dowty H, Beaumont K, Wigger-Alberti W, von Mackensen Y, Kroencke U, Hamscho R, Garcet S, Krueger JG, Banfield C, Oemar B. A phase I, randomized, double-blind study to assess the safety, tolerability and efficacy of the topical RORC2 inverse agonist PF-06763809 in participants with mild-to-moderate plaque psoriasis. Clin Exp Dermatol. 2021 Jan;46(1):122-129. doi: 10.1111/ced.14412. Epub 2020 Sep 14.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2018
• Primary Completion (Actual): March 20, 2019
• Study Completion (Actual): March 20, 2019

Study Registration Dates

• First Submitted: March 13, 2018
• First Submitted That Met QC Criteria: March 13, 2018
• First Posted (Actual): March 19, 2018

Study Record Updates

• Last Update Posted (Actual): June 25, 2020
• Last Update Submitted That Met QC Criteria: June 24, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Psoriasis; Topical
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Physiological Effects of Drugs; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dermatologic Agents; Anti-Asthmatic Agents; Respiratory System Agents; Betamethasone; Calcipotriene
• Other Study ID Numbers: C3561001; 2017-002684-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes