Clinical trial NCT04279119: Maximal Usage Pharmacokinetics and Safety of ARQ-151 in Adolescents and Adults With Chronic Plaque Psoriasis
Official title: An Open Label, Phase 1, Maximal Usage Pharmacokinetics and Safety Study of ARQ-151 Cream 0.3% Administered QD in Adolescent and Adult Subjects With Chronic Plaque Psoriasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Plaque Psoriasis
Lead sponsor: Arcutis Biotherapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2020-02-20
Enrollment: 26
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase 1, open label, single arm study in which ARQ-151 cream 0.3% is applied QD for 2 weeks to adolescent subjects with chronic plaque psoriasis involving at least 10% body surface area (BSA) and adult subjects with chronic plaque psoriasis involving at least 20% BSA (excluding scalp).

The objectives of this study are to evaluate the exposure and characterize the plasma pharmacokinetic profile and to assess the safety and tolerability of ARQ-151 cream 0.3% administered once daily for 2 weeks to adolescent and adult subjects with chronic plaque psoriasis.


Eligibility criteria: Inclusion Criteria:

1. Participants legally competent to sign and give informed consent or for adolescents assent with consent of a parent or legal guardian.
2. Males and females ages 12 years and older (inclusive) at the time of consent/assent.
3. Clinical diagnosis of psoriasis vulgaris of at least 3 months duration as determined by the Investigator or through subject interview. Stable disease for the past 4 weeks.
4. Psoriasis vulgaris on the face, extremities, trunk, and/or intertriginous areas involving at least 10% of BSA in adolescents and at least 20% of BSA in adults (excluding the scalp).
5. An Investigator Global Assessment of disease severity of at least Moderate ('3') at Baseline.
6. Females of childbearing potential (FOCBP) must have a negative serum pregnancy test at Screening (Visit 1) and a negative urine pregnancy test at Baseline (Visit 2). In addition, sexually active FOCBP must agree to use at least one form of highly effective contraception throughout the trial.
7. Females of non-childbearing potential should be premenarchal, post-menopausal with spontaneous amenorrhea for at least 12 months or have undergone surgical sterilization.
8. Subjects in good health as judged by the Investigator, based on medical history, physical examination, vital signs, 12-lead electrocardiogram, serum chemistry labs, hematology values, and urinalysis.
9. Subjects are considered reliable and capable of adhering to the Protocol and visit schedule, according to the judgment of the Investigator.

Exclusion Criteria:

1. Subjects who cannot discontinue medication and treatments prior to the Baseline visit and during the study according to Excluded Medications and Treatments (Table 1).
2. Planned excessive exposure of treated area(s) to either natural or artificial sunlight, tanning bed or other light emitting diode (LED).
3. Subjects currently taking lithium or antimalarial drugs.
4. Planned initiation or changes to concomitant medication that could, in the opinion of the Investigator, affect psoriasis vulgaris (e.g. beta blockers, ACE inhibitors).
5. Current diagnosis of non-plaque form of psoriasis (e.g., guttate, erythrodermic/exfoliative, or pustular psoriasis). Current diagnosis of drug-induced psoriasis.
6. Subjects with any condition on the treatment area which, in the opinion of the Investigator, could confound efficacy measurements.
7. Known allergies to excipients in ARQ-151 cream
8. Subjects who cannot discontinue the use of systemic strong P 450 cytochrome inhibitors (e.g., indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, fluconazole, nefazodone, saquinavir, suboxone and telithromycin) for two weeks prior to the Baseline visit and during the study period.
9. Subjects who cannot discontinue the use of systemic strong P 450 cytochrome inducers (e.g., efavirenz, nevirapine, glucocorticoids, barbiturates (including phenobarbital), phenytoin, rifampin and carbamazepine) for two weeks prior to the Baseline visit and during the study period.
10. Females who are pregnant, wishing to become pregnant during the study, or are breast-feeding.
11. Subjects who have received oral roflumilast (Daliresp®, Daxas®) or other PDE4 inhibitors (apremilast) within the past 4 weeks.
12. Known or suspected:

    * severe renal insufficiency or moderate to severe liver impairment (Child-Pugh B or C)
    * known HIV infection
    * hypersensitivity to component(s) of the investigational products
    * history of severe depression, suicidal ideation, Baseline/Screening C-SSRS indicative of suicidal ideation, whether lifetime or recent/current
13. Adult subjects with PHQ-8 ≥10 or adolescent subjects with modified PHQ-A ≥10 at Screening or Baseline visits.
14. Subjects with a history of chronic alcohol or drug abuse within 6 months of initiation of investigational product.
15. Subjects with a history of a major surgery within 4 weeks prior to Baseline (Visit 2) or has a major surgery planned during the study.
16. 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. For adolescent subjects; parent(s)/legal guardian(s) who are unable to communicate, read, or understand the local language.
17. Subjects who are family members of the clinical study site, clinical study staff, or Sponsor.
18. 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.
19. 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.
20. Subjects with active infection that required oral or intravenous administration of antibiotics, antifungal or antiviral agents within 7 days of Baseline/Day 1.

Primary outcomes:
measure: Maximum concentration (Cmax) of roflumilast and its major N-oxide metabolite
timeFrame: 5 weeks
measure: Area under the plasma concentration-time curve until the last quantifiable timepoint (AUC) for roflumilast and its N-oxide metabolite
timeFrame: 5 weeks
measure: Time of maximum concentration (Tmax) of roflumilast and its major N-oxide metabolite
timeFrame: 5 weeks
Secondary outcomes:
measure: Subject incidence of adverse events
timeFrame: 5 weeks
measure: Incidence of application site reactions
timeFrame: 5 weeks
measure: Incidence of application site reactions
timeFrame: 5 weeks
measure: The incidence of suicide ideation as measured by the Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: 5 weeks
measure: The incidence of changes from baseline in the Patient Health Questionnaire (PHQ-8) Depression Scale
timeFrame: 5 weeks
measure: The incidence of changes from baseline in the Patient Health Questionnaire for Adolescents (PHQ-A) Depression Scale
timeFrame: 5 weeks
Other outcomes:
Locations:
city: Rogers
country: United States
facility: Arcutis Clinical Site 09
state: Arkansas
city: Fountain Valley
country: United States
facility: Arcutis Clinical Site 11
state: California
city: Coral Gables
country: United States
facility: Arcutis Clinical Site 07
state: Florida
city: Doral
country: United States
facility: Arcutis Clinical Site 03
state: Florida
city: Hialeah
country: United States
facility: Arcutis Clinical Site 06
state: Florida
city: Miami
country: United States
facility: Arcutis Clinical Site 12
state: Florida
city: Sanford
country: United States
facility: Arcutis Clinical Site 04
state: Florida
city: Plainfield
country: United States
facility: Arcutis Clinical Site 02
state: Indiana
city: Dublin
country: United States
facility: Arcutis Clinical Site 01
state: Ohio
city: Arlington
country: United States
facility: Arcutis Clinical Site 10
state: Texas
city: San Antonio
country: United States
facility: Arcutis Clinical Site 05
state: Texas
city: Richmond
country: United States
facility: Arcutis Clinical Site 08
state: Virginia
Study officials:
affiliation: Arcutis Biotherapeutics, Inc.
name: David Berk, MD
role: STUDY_DIRECTOR
References: