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

Phase 1

Completed

• Conditions: Psoriasis
• Interventions: Drug: ARQ-151 cream 0.5%; Drug: ARQ-151 cream 0.15%; Drug: ARQ-151 vehicle cream

• Registration Number: NCT03392168
• Lead Sponsor: Arcutis Biotherapeutics, Inc.

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).

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 Timeline

• Study Start: 2017-12-11
• Study First Submitted: 2017-12-29
• Study First Submitted QC: 2018-01-02
• Study First Posted: 2018-01-05
• Primary Completion: 2018-05-02
• Study Completion: 2018-05-02
• Disposition First Submitted: 2020-03-09
• Results First Submitted: 2021-04-29
• Results First Submitted QC: 2021-06-15
• Disposition First Submitted QC: 2021-06-15
• Results First Posted: 2021-07-08
• Disposition First Posted: 2021-07-08
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-02
• Last Update Posted: 2022-08-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 91

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 2 - ARQ-151 cream 0.5%	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
Cohort 2 - ARQ-151 cream 0.15%	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
Cohort 2 - ARQ-151 vehicle cream	ARQ-151 vehicle cream	Vehicle cream applied daily for 28 days to all psoriatic plaques, not exceeding an application area of 5% BSA
Cohort 1 - ARQ-151 cream 0.5%	ARQ-151 cream 0.5%	Single-dose application of ARQ-151 cream 0.5% to 25 cm\^2 of psoriatic plaque(s)

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline in 4 Week Target Plaque Severity Score x Target Plaque Area in Cohort 2	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

Name	Time	Method
Percent Change From Baseline in Target Plaque Area in Cohort 2	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.
Percent Change From Baseline in 1, 2, 3 Week Target Plaque Severity Score x Target Plaque Area in Cohort 2	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.
Percent Change From Baseline in Total Plaque Severity Score in Cohort 2	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.

Trial Locations

Locations (8)

Mosaic Dermatology; 🇺🇸 Santa Monica, California, United States

Research by ICLS; 🇨🇦 Oakville, Ontario, Canada

SKiN Centre for Dermatology; 🇨🇦 Peterborough, Ontario, Canada

Dr. Chih-ho Hong Medical Inc.; 🇨🇦 Surrey, British Columbia, Canada

Lynderm Research Inc.; 🇨🇦 Markham, Ontario, Canada

K. Papp Clinical Research Inc.; 🇨🇦 Waterloo, Ontario, Canada

The Centre for Dermatology; 🇨🇦 Richmond Hill, Ontario, Canada

XLR8 Medical Research Inc.; 🇨🇦 Windsor, Ontario, Canada