Long-Term Safety of ARQ-151 Cream in Adult Subjects With Chronic Plaque Psoriasis

Study Overview
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Brief Summary
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This is an open-label, long-term safety study of roflumilast (ARQ-151) 0.3% cream in subjects with chronic plaque psoriasis involving up to 25% total Body Surface Area (BSA). Study medication will be applied by the qualifying subjects topically once daily for 52 weeks at home. Periodic clinic visits will include assessments for clinical safety, application site reactions, and disease improvement or progression.

Detailed Description
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Cohort 1 of this study consisted of participants who previously completed study ARQ-151-201 (NCT03638258), and Cohort 2 consisted of participants who were not previously enrolled in ARQ-151-201.

Official Title
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A Phase 2, Multicenter, Open-Label Extension Study of the Long-Term Safety of ARQ-151 Cream 0.3% in Adult Subjects With Chronic Plaque Psoriasis Who Have Completed Preceding Study ARQ-151-201 Phase 2 Randomized Controlled Trial (Cohort 1) and Non-ARQ-151-201 Subjects (Cohort 2)

Conditions
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Plaque Psoriasis

Intervention / Treatment
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* Drug: Roflumilast


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants legally competent to sign and give informed consent Males and females ages 18 years and older Subjects with chronic plaque psoriasis who met eligibility criteria for ARQ-151-201, successfully completed ARQ-151-201 through Week 12, and are able to enroll into this long-term safety study on the Week 12 visit of the previous study (ARQ-151-201). Females of childbearing potential (FOCBP) must have a negative urine pregnancy test at all study visits. In addition, sexually active FOCBP must agree to use at least one form of highly effective contraception throughout the trial. Highly effective forms of contraception include: oral/implant/injectable/transdermal contraceptives, intrauterine device, or partner's vasectomy. If barrier methods are used (e.g., condom with spermicide, diaphragm with spermicide), then 2 forms of conception are required. The use of abstinence as a contraceptive measure is acceptable as long as this is a consistent part of a lifestyle choice and a backup method has been identified if the subject becomes sexually active. Post-menopausal women with spontaneous amenorrhea for at least 12 months or have undergone surgical sterilization (permanent sterilization methods include hysterectomy, bilateral oophorectomy, hysteroscopic sterilization, bilateral tubal ligation or bilateral salpingectomy). Exclusion Criteria: Subjects who experienced an ARQ-151 treatment-related AE or a serious AE (SAE) that precluded further treatment with ARQ-151 cream in Study ARQ-151-201. Subjects that use any Excluded Medications and Treatments Current diagnosis of guttate, erythrodermic/exfoliative, palmoplantar, or pustular psoriasis. Subjects who cannot discontinue the use of strong P-450 cytochrome inhibitors e.g., indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone, saquinavir, suboxone and telithromycin during the study period. Subjects who cannot discontinue the use of strong P-450 cytochrome inducers e.g., efavirenz, nevirapine, glucocorticoids, barbiturates (including phenobarbital), phenytoin, and rifampin during the study period. Known or suspected: severe renal insufficiency or severe hepatic disorders hypersensitivity to component(s) of the investigational products history of severe depression, suicidal ideation Females who are pregnant, wishing to become pregnant during the study, or are breast-feeding. 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. Current or a history of cancer within 5 years with the exception of fully treated skin basal cell carcinoma, cutaneous squamous cell carcinoma or carcinoma in situ of the cervix. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Note: Subjects that consent to enter this open-label safety study have previously completed a companion study (ARQ-151-201 Phase 2 randomized controlled trial)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Long-term Safety of Roflumilast<br>Participants applied roflumilast (ARQ-151) cream 0.3% once daily for 52 weeks | Drug: Roflumilast<br>* Roflumilast cream 0.3% for topical application<br>* Other names: ARQ-151;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing ≥1 Treatment-emergent Adverse Event (TEAE) | An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. All AEs that began after initiating study treatment (treatment-emergent AEs [TEAEs]) in ARQ-151-202 are presented. | Up to 52 weeks | 
| Number of Participants Experiencing ≥1 Serious Adverse Event (SAE) | An SAE is any AE that in the view of either the PI or Sponsor, results in any of the following outcomes: Death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. | Up to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With an Investigator Global Assessment (IGA) Score of 'Clear' or 'Almost Clear' | The number of participants with an IGA score of 0 ('clear') or 1 ('almost clear') at Week 12 is reported. The IGA is a 5-point scale assessing the severity of plaque psoriasis, with scores ranging from 0 ('clear') to 4 ('severe'), and higher scores indicate greater plaque severity. | Weeks 12, 24, 36, and 52 | 
| Duration of Response in Participants Achieving 'Clear' IGA Score | The median time to re-starting study therapy among participants who achieve a 'clear' IGA score and stop treatment to all lesions is presented. | Up to 52 weeks | 
| Number of Participants With Intertriginous Area Involvement Achieving an Intertriginous Area Investigator Global Assessment (I-IGA) Score of Clear' or 'Almost Clear' | The number of participants who had intertriginous area involvement with an I-IGA score of 'clear' or 'almost clear' is presented. The I-IGA is 5-point scale assessing the severity of plaque psoriasis in the intertriginous area, with scores ranging from 0 ('clear') to 4 ('severe'), and higher scores indicate greater plaque severity. | Weeks 12, 24, 36, and 52 | 
| Number of Participants Achieving a 75% Reduction From Baseline in Modified Psoriasis Severity Index (mPASI-75) | The number of participants 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 and Weeks 12, 24, 36, and 52 |