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

• ClinicalTrials.gov Identifier: NCT03638258
• Recruitment Status: Completed
• First Posted: August 20, 2018
• Results First Posted: August 10, 2022
• Last Update Posted: September 2, 2022
• Sponsor: Arcutis Biotherapeutics, Inc.
• Information provided by (Responsible Party): Arcutis Biotherapeutics, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Plaque Psoriasis	Drug: Roflumilast Cream 0.3%; Drug: Roflumilast Cream 0.15%; Drug: Vehicle Cream	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 331 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Parallel group, double blind, vehicle-controlled study
• Masking: Double (Participant, Investigator)
• Masking Description: Roflumilast drug product will be supplied as a 0.3% and 0.15% cream. The matching vehicle cream will contain only excipients of roflumilast cream.
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: September 21, 2018
• Actual Primary Completion Date: May 29, 2019
• Actual Study Completion Date: May 29, 2019

Arms and Interventions

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 Name: 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 Name: 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

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With an Investigator Global Assessment (IGA) Score of 'Clear' or 'Almost Clear' at Week 6 [ Time Frame: 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.

Secondary Outcome Measures :

1. Percentage of Participants With an Investigator Global Assessment (IGA) Score of 'Clear' or 'Almost Clear' [ Time Frame: Weeks 4, 8, and 12 ]
   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.
2. Change From Baseline in Modified Psoriasis Area Severity Index (mPASI) Score [ Time Frame: Baseline (Day 1) and Weeks 4, 6, 8, and 12 ]
   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.
3. Percent Change From Baseline in Body Surface Area (BSA) Affected [ Time Frame: Baseline (Day 1) and Weeks 4, 6, 8, and 12 ]
   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.
4. Percentage of Participants With an Investigator Global Assessment (IGA) Score of 'Clear' or 'Almost Clear' Plus a 2-Grade Improvement From Baseline [ Time Frame: Baseline (Day 1) and Weeks 4, 6, 8, and 12 ]
   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.
5. 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 [ Time Frame: Weeks 4, 6, 8, and 12 ]
   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.
6. Change From Baseline in Worst Itch-Numeric Rating Scale (WI-NRS) Pruritus Score [ Time Frame: Baseline (Day 1) and Weeks 4, 6, 8, and 12 ]
   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.
7. Percentage of Participants With Baseline Worst Itch-Numeric Rating Scale (WI-NRS) Pruritus Score ≥6 Who Experienced a 4-point Reduction [ Time Frame: Baseline (Day 1) and Weeks 4, 6, 8, and 12 ]
   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.
8. Percentage of Participants Achieving a Modified Psoriasis Area Severity Index-75 (mPASI-75) Compared to Baseline [ Time Frame: Baseline (Day 1) and Weeks 4, 6, 8, and 12 ]
   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.
9. Percentage of Participants Achieving a Modified Psoriasis Area Severity Index-90 (mPASI-90) Compared to Baseline [ Time Frame: Baseline (Day 1) and Weeks 4, 6, 8, and 12 ]
   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.
10. Change From Baseline in Psoriasis Symptom Diary (PSD) Total Score [ Time Frame: Baseline (Day 1) and Weeks 4, 6, 8, and 12 ]
    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.
11. Change From Baseline in Itch-Related Sleep Loss Numeric Rating Scale (NRS) Score [ Time Frame: Baseline (Day 1) and Weeks 4, 6, 8, and 12 ]
    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.
12. Change From Baseline in Dermatology Life Quality Index (DLQI) Score [ Time Frame: Baseline (Day 1) and Weeks 4, 6, 8, and 12 ]
    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.
13. Responses to Individual Questions of the Psoriasis Symptom Diary (PSD) [ Time Frame: Weeks 4, 6, 8, and 12 ]
    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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, California

Arcutis Clinical Site 35

Beverly Hills, California, United States, 90212

Arcutis Clinical Site 29

Northridge, California, United States, 91324

Arcutis Clinical Site 28

San Diego, California, United States, 92123

Arcutis Clinical Site 27

Santa Monica, California, United States, 90403

United States, Florida

Arcutis Clinical Site 12

Miami, Florida, United States, 33144

Arcutis Clinical Site 16

Sanford, Florida, United States, 32771

United States, Kentucky

Arcutis Clinical Site 21

Louisville, Kentucky, United States, 40217

United States, Michigan

Arcutis Clinical Site 34

Clinton Township, Michigan, United States, 48038

Arcutis Clinical Site 33

Detroit, Michigan, United States, 48202

United States, Minnesota

Arcutis Clinical Site 20

Fridley, Minnesota, United States, 55432

United States, New York

Arcutis Clinical Site 22

New York, New York, United States, 10029

United States, North Carolina

Arcutis Clinical Site 14

High Point, North Carolina, United States, 27262

United States, Ohio

Arcutis Clinical Site 39

Bexley, Ohio, United States, 43209

United States, Pennsylvania

Arcutis Clinical Site 15

Pittsburgh, Pennsylvania, United States, 15213

United States, Texas

Arcutis Clinical Site 19

College Station, Texas, United States, 77845

Arcutis Clinical Site 37

Houston, Texas, United States, 77004

Arcutis Clinical Site 13

Houston, Texas, United States, 77056

Arcutis Clinical Site 23

San Antonio, Texas, United States, 78213

Arcutis Clinical Site 24

Webster, Texas, United States, 77598

United States, Virginia

Arcutis Clinical Site 31

Norfolk, Virginia, United States, 23502

Canada, British Columbia

Arcutis Clinical Site 18

Surrey, British Columbia, Canada, V3R 6A7

Arcutis Clinical Site 11

Surrey, British Columbia, Canada, V3V 0C6

Canada, Manitoba

Arcutis Clinical Site 38

Winnipeg, Manitoba, Canada, R3M 3Z4

Canada, Ontario

Arcutis Clinical Site 10

Ajax, Ontario, Canada, L1S 7K8

Arcutis Clinical Site 25

London, Ontario, Canada, N6H 5L5

Arcutis Clinical Site 26

Markham, Ontario, Canada, L3P 1X2

Arcutis Clinical Site 32

Oakville, Ontario, Canada, L6J 7W5

Arcutis Clinical Site 17

Peterborough, Ontario, Canada, K9J 5K2

Arcutis Clinical Site 30

Waterloo, Ontario, Canada, N2J 1C4

Arcutis Clinical Site 36

Windsor, Ontario, Canada, N8W 1E6

Sponsors and Collaborators

Arcutis Biotherapeutics, Inc.

Investigators

• Study Director: David Berk, MD; Arcutis Biotherapeutics, Inc.

  Study Documents (Full-Text)

Documents provided by Arcutis Biotherapeutics, Inc.:

Study Protocol  [PDF] November 12, 2018

Statistical Analysis Plan  [PDF] May 30, 2019

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. 2023 Mar;24(2):305-313. doi: 10.1007/s40257-022-00739-3. Epub 2022 Nov 12.

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.

• Responsible Party: Arcutis Biotherapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03638258
• Other Study ID Numbers: ARQ-151-201
• First Posted: August 20, 2018
• Results First Posted: August 10, 2022
• Last Update Posted: September 2, 2022
• Last Verified: August 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases