Safety, Pharmacokinetics and Efficacy of ARQ-151 Cream in Adults With Mild to Moderate Chronic Plaque Psoriasis

• ClinicalTrials.gov Identifier: NCT03392168
• Recruitment Status: Completed
• First Posted: January 5, 2018
• Results First Posted: July 8, 2021
• Last Update Posted: July 8, 2021
• Sponsor: Arcutis Biotherapeutics, Inc.
• Information provided by (Responsible Party): Arcutis Biotherapeutics, Inc.

Study Description

Brief Summary:

This study assessed the safety and pharmacokinetics (PK) of a single dose application of ARQ-151 cream 0.5% to 25 cm^2 of psoriatic plaque(s) (Cohort 1). The study also assessed the safety, PK and efficacy of ARQ-151 cream 0.5% vs vehicle and ARQ-151 cream 0.15% vs vehicle applied once a day for 28 days to individuals with 0.5% to 5.0% body surface area (BSA) of chronic plaque psoriasis (Cohort 2).

Condition or disease	Intervention/treatment	Phase
Psoriasis	Drug: ARQ-151 cream 0.5%; Drug: ARQ-151 cream 0.15%; Drug: ARQ-151 vehicle cream	Phase 1; Phase 2

Detailed Description:

There were 2 cohorts of participants. Cohort 1 was a single dose study of ARQ-151 0.5% cream applied to 25 cm^2 of psoriatic plaque(s) in 8 psoriasis participants. Cohort 2 was a parallel group, double blind, vehicle controlled study in which ARQ-151 cream 0.5%, ARQ-151 cream 0.15% or vehicle cream was applied once a day for 28 days to participants with between 0.5% to 5.0% BSA of chronic plaque psoriasis. Participants were adult (≥18 years old) males or females with chronic plaque psoriasis.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 91 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Cohort 1 was open label. Cohort 2 was double blind.
• Primary Purpose: Treatment
• Official Title: A Phase 1/2a Single Dose and 28-day Parallel Group, Double Blind, Vehicle-Controlled Study of the Safety, Pharmacokinetics and Efficacy of ARQ-151 Cream 0.5% and 0.15% in Adults With Mild to Moderate Chronic Plaque Psoriasis
• Actual Study Start Date: December 11, 2017
• Actual Primary Completion Date: May 2, 2018
• Actual Study Completion Date: May 2, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1 - ARQ-151 cream 0.5%; Single-dose application of ARQ-151 cream 0.5% to 25 cm^2 of psoriatic plaque(s)	Drug: ARQ-151 cream 0.5%; 0.5% active concentration
Experimental: Cohort 2 - ARQ-151 cream 0.5%; ARQ-151 cream 0.5% applied daily for 28 days to all psoriatic plaques, not exceeding an application area of 5% BSA	Drug: ARQ-151 cream 0.5%; 0.5% active concentration
Experimental: Cohort 2 - ARQ-151 cream 0.15%; ARQ-151 cream 0.15% applied daily for 28 days to all psoriatic plaques, not exceeding an application area of 5% BSA	Drug: ARQ-151 cream 0.15%; 0.15% active concentration
Placebo Comparator: Cohort 2 - ARQ-151 vehicle cream; Vehicle cream applied daily for 28 days to all psoriatic plaques, not exceeding an application area of 5% BSA	Drug: ARQ-151 vehicle cream; Vehicle cream

Outcome Measures

Primary Outcome Measures :

1. Percent Change From Baseline in 4 Week Target Plaque Severity Score x Target Plaque Area in Cohort 2 [ Time Frame: Baseline and Week 4 ]
   Difference in least squares mean percent change from baseline at Week 4 in the product of target plaque severity score (TPSS) x target plaque area (TPA) between each dose concentration level of ARQ-151 cream and vehicle using mixed model repeated measures (MMRM) analysis with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects and baseline TPSS x TPA score as a covariate. For TPSS, all target lesions were scored individually for signs of induration, scaling, and erythema using a 5-point severity scale: 0 = none; 1 = mild; 2 = moderate; 3 = severe; 4 = very severe. TPA (cm^2) was determined by multiplying the longest diameter (cm) of the target plaque by the widest perpendicular diameter (cm) (perpendicular to the longest diameter of the target plaque). A negative percent change indicates improvement.

Secondary Outcome Measures :

1. Percent Change From Baseline in 1, 2, 3 Week Target Plaque Severity Score x Target Plaque Area in Cohort 2 [ Time Frame: Baseline and Weeks 1, 2 and 3 ]
   Difference in least squares mean percent change from baseline at Weeks 1, 2 and 3 in target plaque severity score (TPSS) x target plaque area (TPA) between each dose concentration level of ARQ-151 cream and vehicle using mixed model repeated measures (MMRM) analysis with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects and baseline TPSS x TPA score as a covariate. For TPSS, all target lesions were scored individually for signs of induration, scaling, and erythema using a 5-point severity scale: 0 = none; 1 = mild; 2 = moderate; 3 = severe; 4 = very severe. TPA (cm^2) was determined by multiplying the longest diameter (cm) of the target plaque by the widest perpendicular diameter (cm) (perpendicular to the longest diameter of the target plaque). A negative percent change indicates improvement.
2. Percent Change From Baseline in Total Plaque Severity Score in Cohort 2 [ Time Frame: Baseline and Weeks 1, 2, 3, and 4 ]
   Difference in least squares mean percent change from baseline at Weeks 1, 2, 3 and 4 in total plaque severity score (TPSS) between each dose concentration level of ARQ-151 cream and vehicle using mixed model repeated measures (MMRM) analysis with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects and baseline TPSS score as a covariate. For TPSS, all target lesions were scored individually for signs of induration, scaling, and erythema using a 5-point severity scale: 0 = none; 1 = mild; 2 = moderate; 3 = severe; 4 = very severe. A negative percent change indicates improvement.
3. Percent Change From Baseline in Target Plaque Area in Cohort 2 [ Time Frame: Baseline and Weeks 1, 2, 3, and 4 ]
   Difference in least squares mean percent change from baseline at Weeks 1, 2, 3, and 4 in target plaque area (TPA) between each dose concentration level of ARQ-151 cream and vehicle using mixed model repeated measures (MMRM) analysis with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects and baseline TPA score as a covariate. Target plaque area (cm^2) was determined by multiplying the longest diameter (cm) of the target plaque by the widest perpendicular diameter (cm) (perpendicular to the longest diameter of the target plaque). A negative percent change indicates improvement.

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:

• Adult male and female participants aged ≥18 years.
• In Cohort 1, participants must have at least 25 cm^2 of chronic plaque psoriasis (excluding the face, scalp, intertriginous areas, palms and soles).
• In Cohort 2, participants must have 0.5% to 5.0% of total BSA of chronic plaque psoriasis and at least one target plaque, of at least 9 cm^2 in size with a TPSS ≥4 (excluding the face, scalp, intertriginous areas, palms and soles).
• Women of childbearing potential must have a negative urine pregnancy test at Screening and agree to use birth control throughout the trial.
• In good health as judged by the Investigator, based on medical history, physical examination, 12-lead electrocardiogram (ECG), serum chemistry labs, hematology values, and urinalysis.
• Participants agree not to have prolonged sun exposure during the course of the study. Tanning bed use is not allowed.
• Participants are competent to sign and give informed consent and considered reliable and capable of adhering to the Protocol and visit schedule.

Exclusion Criteria:

• Participants with non-plaque forms of psoriasis (erythrodermic, guttate, pustular or palmo-plantar psoriasis) or with drug-induced psoriasis.
• Evidence of skin conditions other than psoriasis that would interfere with evaluation of the effect of the study medication.
• Pregnant or lactating women or women planning to become pregnant during the study and / or within 28 days following the last dose of study medication.
• Known allergies to excipients in ARQ-151 cream.
• Participants who cannot discontinue the use of strong P-450 cytochrome inducers or inhibitors for two weeks prior to the baseline visit and during the study period.
• Participants who are unwilling to refrain from using a tanning bed for 2 weeks before and during the study.
• Participants who cannot discontinue systemic therapies and/or topical therapies for the treatment of psoriasis.
• Participants with a history of chronic alcohol or drug abuse in past 6 months.
• History of and/or concurrent condition of serious hypersensitivity (anaphylactic shock or anaphylactoid reaction) to phosphodiesterase type 4 (PDE-4) inhibitors.
• Current or a history of cancer within 5 years with the exception of fully excised skin basal cell carcinoma, cutaneous squamous cell carcinoma or carcinoma in situ of the cervix.
• Participants with active infection that requires oral or intravenous administration of antibiotics, antifungal or antiviral agents.
• Participants who are unable to communicate, read or understand language, or who display another condition which makes them unsuitable for clinical study participation.

Contacts and Locations

Locations

United States, California

Mosaic Dermatology

Santa Monica, California, United States, 90403

Canada, British Columbia

Dr. Chih-ho Hong Medical Inc.

Surrey, British Columbia, Canada, V3R 6A7

Canada, Ontario

Lynderm Research Inc.

Markham, Ontario, Canada, L3P 1X2

Research by ICLS

Oakville, Ontario, Canada, L6J 7W5

SKiN Centre for Dermatology

Peterborough, Ontario, Canada, K9J 5K2

The Centre for Dermatology

Richmond Hill, Ontario, Canada, L4B 1A5

K. Papp Clinical Research Inc.

Waterloo, Ontario, Canada, N2J 1C4

XLR8 Medical Research Inc.

Windsor, Ontario, Canada, N8W 1E6

Sponsors and Collaborators

Arcutis Biotherapeutics, Inc.

Investigators

• Study Director: Howard Welgus, M.D.; Arcutis Biotherapeutics, Inc.

  Study Documents (Full-Text)

Documents provided by Arcutis Biotherapeutics, Inc.:

Study Protocol  [PDF] March 19, 2018

Statistical Analysis Plan  [PDF] May 6, 2018

More Information

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

Papp KA, Gooderham M, Droege M, Merritt C, Osborne DW, Berk DR, Thurston AW, Smith VH, Welgus H. Roflumilast Cream Improves Signs and Symptoms of Plaque Psoriasis: Results from a Phase 1/2a Randomized, Controlled Study. J Drugs Dermatol. 2020 Aug 1;19(8):734-740. doi: 10.36849/JDD.2020.5370.

• Responsible Party: Arcutis Biotherapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03392168
• Other Study ID Numbers: ARQ-151-101
• First Posted: January 5, 2018
• Results First Posted: July 8, 2021
• Last Update Posted: July 8, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Arcutis Biotherapeutics, Inc.:

Psoriasis; Plaque Psoriasis

Additional relevant MeSH terms:

Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases