The Safety, Efficacy and Pharmacokinetics of ARQ-151 Cream in Subjects With Chronic Plaque Psoriasis (ARQ-151-201)

A Phase 2b 12-Week Parallel Group, Double Blind, Vehicle-Controlled Study of the Safety, Efficacy and Pharmacokinetics of ARQ-151 Cream 0.3% and ARQ-151 Cream 0.15% Administered Once Daily in Subjects With Chronic Plaque Psoriasis

This is a parallel group, double blind, vehicle-controlled study in which roflumilast (ARQ-151) cream 0.3%, roflumilast cream 0.15%, or vehicle cream is applied once daily (QD) for 84 days to subjects with chronic plaque psoriasis involving between 2 and 20% body surface area.

Study Overview

• Status: Completed
• Conditions: Plaque Psoriasis
• Intervention / Treatment: Drug: Roflumilast Cream 0.3%; Drug: Roflumilast Cream 0.15%; Drug: Vehicle Cream

• Study Type: Interventional
• Enrollment (Actual): 331
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Surrey, British Columbia, Canada, V3R 6A7
      • Arcutis Clinical Site 18
    • Surrey, British Columbia, Canada, V3V 0C6
      • Arcutis Clinical Site 11
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3M 3Z4
      • Arcutis Clinical Site 38
  • Ontario
    • Ajax, Ontario, Canada, L1S 7K8
      • Arcutis Clinical Site 10
    • London, Ontario, Canada, N6H 5L5
      • Arcutis Clinical Site 25
    • Markham, Ontario, Canada, L3P 1X2
      • Arcutis Clinical Site 26
    • Oakville, Ontario, Canada, L6J 7W5
      • Arcutis Clinical Site 32
    • Peterborough, Ontario, Canada, K9J 5K2
      • Arcutis Clinical Site 17
    • Waterloo, Ontario, Canada, N2J 1C4
      • Arcutis Clinical Site 30
    • Windsor, Ontario, Canada, N8W 1E6
      • Arcutis Clinical Site 36
• United States
  • California
    • Beverly Hills, California, United States, 90212
      • Arcutis Clinical Site 35
    • Northridge, California, United States, 91324
      • Arcutis Clinical Site 29
    • San Diego, California, United States, 92123
      • Arcutis Clinical Site 28
    • Santa Monica, California, United States, 90403
      • Arcutis Clinical Site 27
  • Florida
    • Miami, Florida, United States, 33144
      • Arcutis Clinical Site 12
    • Sanford, Florida, United States, 32771
      • Arcutis Clinical Site 16
  • Kentucky
    • Louisville, Kentucky, United States, 40217
      • Arcutis Clinical Site 21
  • Michigan
    • Clinton Township, Michigan, United States, 48038
      • Arcutis Clinical Site 34
    • Detroit, Michigan, United States, 48202
      • Arcutis Clinical Site 33
  • Minnesota
    • Fridley, Minnesota, United States, 55432
      • Arcutis Clinical Site 20
  • New York
    • New York, New York, United States, 10029
      • Arcutis Clinical Site 22
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • Arcutis Clinical Site 14
  • Ohio
    • Bexley, Ohio, United States, 43209
      • Arcutis Clinical Site 39
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Arcutis Clinical Site 15
  • Texas
    • College Station, Texas, United States, 77845
      • Arcutis Clinical Site 19
    • Houston, Texas, United States, 77004
      • Arcutis Clinical Site 37
    • Houston, Texas, United States, 77056
      • Arcutis Clinical Site 13
    • San Antonio, Texas, United States, 78213
      • Arcutis Clinical Site 23
    • Webster, Texas, United States, 77598
      • Arcutis Clinical Site 24
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Arcutis Clinical Site 31

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:

• Participants legally competent to sign and give informed consent
• Males and females ages 18 years and older (inclusive)
• Clinical diagnosis of psoriasis vulgaris of at least 6 months duration as determined by the Investigator
• Females of childbearing potential (FOCBP) must have a negative urine pregnancy test at Screening (Visit 1) and Baseline (Visit 2). In addition, sexually active FOCBP must agree to use at least one form of highly effective contraception throughout the trial.
• In good health as judged by the Investigator, based on medical history, physical examination, serum chemistry labs, hematology values, and urinalysis.
• Subjects are considered reliable and capable of adhering to the Protocol and visit schedule, according to the judgment of the Investigator.

Exclusion Criteria:

• Planned excessive exposure of treated area(s) to either natural or artificial sunlight or tanning bed.
• Females who are pregnant, wishing to become pregnant during the study, or are breast-feeding.
• Previous treatment with roflumilast cream or its active ingredient
• Subjects with any serious medical condition or laboratory abnormality that would prevent study participation or place the subject at significant risk, as determined by the Investigator.
• Subjects with a history of chronic alcohol or drug abuse within 6 months of initiation of study medication.
• Subjects who are unable to communicate, read or understand the local language, or who display another condition, which in the Investigator's opinion, makes them unsuitable for clinical study participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Roflumilast Cream 0.3%; Roflumilast cream 0.3% topically applied QD for 12 weeks.	Drug: Roflumilast Cream 0.3%; Applied once daily for 12 weeks; Other Names: ARQ-151
Experimental: Roflumilast Cream 0.15%; Roflumilast cream 0.15% topically applied QD for 12 weeks.	Drug: Roflumilast Cream 0.15%; Applied once daily for 12 weeks; Other Names: ARQ-151
Placebo Comparator: Vehicle Cream; Vehicle cream matched to roflumilast cream (containing only excipients of active cream) applied QD for 12 weeks.	Drug: Vehicle Cream; Applied once daily for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With an Investigator Global Assessment (IGA) Score of 'Clear' or 'Almost Clear' at Week 6	The percentage of participants with an IGA score of 0 ('clear') or 1 ('almost clear') at Week 6 is reported. The IGA is 5-point scale assessing the severity of plaque psoriasis, with scores ranging from 0 ('clear') to 4 ('severe'), with higher scores indicating greater plaque severity.	Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With an Investigator Global Assessment (IGA) Score of 'Clear' or 'Almost Clear'	The percentage of participants with an IGA score of 0 ('clear') or 1 ('almost clear') is reported. The IGA is 5-point scale assessing the severity of plaque psoriasis, with scores ranging from 0 ('clear') to 4 ('severe'), with higher scores indicating greater plaque severity.	Weeks 4, 8, and 12
Change From Baseline in Modified Psoriasis Area Severity Index (mPASI) Score	The percent change from baseline in mPASI score is presented. The mPASI combines the assessment of the severity of lesions and the area affected into a single score ranging from 0 ('no disease') to 72 ('maximal disease'), with higher scores indicating greater severity. For scoring, the body is divided into four sections (head [h]: 10% of a person's skin; arms [a] 20%; trunk [t] 30%; legs (l] 40%); for each section, the percent of area involved is estimated from 0 (0% involved) to 6 (90 to 100% involved). Then, within each area, the severity is estimated by three clinical signs: erythema ('E'; redness), induration ('T'; thickness), and desquamation ('S'; scaling). Severity parameters are measured on a scale of 0 to 4, from none to maximum severity possible. Each of these areas is scored by itself, and then the four scores are combined into the final mPASI, using the formula mPASI = 0.1 (Eh + Th + Sh) Ah + 0.2 (Ea + Ta + Sa) Aa + 0.3 (Et + Tt + St) At + 0.4 (El + Tl + Sl) Al.	Baseline (Day 1) and Weeks 4, 6, 8, and 12
Percent Change From Baseline in Body Surface Area (BSA) Affected	The BSA affected by psoriasis was determined by the subject's hand method, where the subject's hand (including fingers) surface area was assumed to equal 1% of BSA. The mean percent change from baseline in BSA is presented.	Baseline (Day 1) and Weeks 4, 6, 8, and 12
Percentage of Participants With an Investigator Global Assessment (IGA) Score of 'Clear' or 'Almost Clear' Plus a 2-Grade Improvement From Baseline	The percentage of participants with an IGA score of 0 ('clear') or 1 ('almost clear') plus a 2-grade improvement from baseline is reported. The IGA is 5-point scale assessing the severity of plaque psoriasis, with scores ranging from 0 ('clear') to 4 ('severe'), with higher scores indicating greater plaque severity.	Baseline (Day 1) and Weeks 4, 6, 8, and 12
Percentage of Participants With an Intertriginous Area Investigator Global Assessment (I-IGA) Score of 'Clear' or 'Almost Clear' Who Had at Least Mild Lesions at Baseline	The percentage of participants (who had intertriginous area involvement with an I-IGA score of at least mild at baseline) with at least a 2-grade improvement in I-IGA score at Weeks 4, 6, 8, and 12 is presented.	Weeks 4, 6, 8, and 12
Change From Baseline in Worst Itch-Numeric Rating Scale (WI-NRS) Pruritus Score	The WI-NRS is a simple, single-item scale to assess the subject-reported severity of this symptom, on a scale ranging from 0 ("no itch") to 10 ("worst imaginable itch") the subject experienced in the previous 24 hours. The mean (SD) change in WI-NRS score from baseline is presented.	Baseline (Day 1) and Weeks 4, 6, 8, and 12
Percentage of Participants With Baseline Worst Itch-Numeric Rating Scale (WI-NRS) Pruritus Score ≥6 Who Experienced a 4-point Reduction	The percentage of participants who had baseline WI-NRS scores ≥6 who achieved a 4-point reduction in WI-NRS score at Weeks 4, 6, 8, and 12 is reported. The WI-NRS is a simple, single item scale to assess the subject-reported severity of this symptom, on a scale ranging from 0 ("no itch") to 10 ("worst imaginable itch") the subject experienced in the previous 24 hours.	Baseline (Day 1) and Weeks 4, 6, 8, and 12
Percentage of Participants Achieving a Modified Psoriasis Area Severity Index-75 (mPASI-75) Compared to Baseline	The percentage of subjects achieving a 75% reduction in mPASI (eg, mPASI-75) score relative to baseline is presented. The mPASI combines the assessment of the severity of lesions and the area affected into a single score ranging from 0 ('no disease') to 72 ('maximal disease'), with higher scores indicating greater severity.	Baseline (Day 1) and Weeks 4, 6, 8, and 12
Percentage of Participants Achieving a Modified Psoriasis Area Severity Index-90 (mPASI-90) Compared to Baseline	The mPASI combines the assessment of the severity of lesions and the area affected into a single score ranging from 0 ('no disease') to 72 ('maximal disease'), with higher scores indicating greater severity. The percentage of subjects achieving a 90% reduction in mPASI (eg, mPASI-90) score relative to baseline is presented.	Baseline (Day 1) and Weeks 4, 6, 8, and 12
Change From Baseline in Psoriasis Symptom Diary (PSD) Total Score	The PSD is a 16-item questionnaire asking subjects to rate the severity of psoriasis-related symptoms in the past 24 hours. Each question is scored from 0 ("no symptoms") to 11 ("worst imaginable symptoms"). Scores range from 0 to 176, with higher scores indicating greater symptom severity. The mean (SD) change in PSD total score relative to baseline is presented for each treatment arm.	Baseline (Day 1) and Weeks 4, 6, 8, and 12
Change From Baseline in Itch-Related Sleep Loss Numeric Rating Scale (NRS) Score	The Itch-Related Sleep Loss NRS is a single item scale scored from 0 ("no itch-related sleep loss") to 10 ("itch-related sleep loss as bad as it could be") assessing the severity of itch-related sleep loss in the past 24 hours. The mean (SD) change from the baseline NRS score is presented for each treatment arm.	Baseline (Day 1) and Weeks 4, 6, 8, and 12
Change From Baseline in Dermatology Life Quality Index (DLQI) Score	The DLQI is a 10-item scale asking subject to rate the severity of symptoms during the past week. Each item is scored from 0 ("not at all" or "not relevant") to 3 or 4 ("very much") [2 questions are scored 0 to 3 and 8 questions are scored 0 to 4]. The total DLQI score ranges from 0 to 48, with higher scores indicating greater symptom severity. The mean (SD) change from baseline DLQI score is presented.	Baseline (Day 1) and Weeks 4, 6, 8, and 12
Responses to Individual Questions of the Psoriasis Symptom Diary (PSD)	Two items from the PSD asking participants to rate the overall severity of psoriasis-related itching and pain during the past 24 hours are presented. Each item is scored on an 11-point scale ranging from 0 ("no symptom") to 10 ("worst imaginable symptom"), with lower scores indicating lower symptoms severity. The mean (SD) score is presented for each treatment arm.	Weeks 4, 6, 8, and 12

Collaborators and Investigators

• Sponsor: Arcutis Biotherapeutics, Inc.

Publications and helpful links

General Publications

• Stein Gold L, Alonso-Llamazares J, Draelos ZD, Gooderham MJ, Kempers SE, Kircik LH, Lebwohl MG, Papp KA, Pariser DM, Toth DP, Yosipovitch G, Higham RC, Feng A, Berk DR. Effect of Roflumilast Cream (ARQ-151) on Itch and Itch-Related Sleep Loss in Adults with Chronic Plaque Psoriasis: Patient-Reported Itch Outcomes of a Phase 2b Trial. Am J Clin Dermatol. 2022 Nov 12. doi: 10.1007/s40257-022-00739-3. Online ahead of print.
• Lebwohl MG, Papp KA, Stein Gold L, Gooderham MJ, Kircik LH, Draelos ZD, Kempers SE, Zirwas M, Smith K, Osborne DW, Trotman ML, Navale L, Merritt C, Berk DR, Welgus H; ARQ-151 201 Study Investigators. Trial of Roflumilast Cream for Chronic Plaque Psoriasis. N Engl J Med. 2020 Jul 16;383(3):229-239. doi: 10.1056/NEJMoa2000073.

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2018
• Primary Completion (Actual): May 29, 2019
• Study Completion (Actual): May 29, 2019

Study Registration Dates

• First Submitted: August 16, 2018
• First Submitted That Met QC Criteria: August 17, 2018
• First Posted (Actual): August 20, 2018

Study Record Updates

• Last Update Posted (Actual): September 2, 2022
• Last Update Submitted That Met QC Criteria: August 31, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: ARQ-151-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No