Clinical trial NCT04156191: Pharmacokinetics (PK), Safety, Efficacy and Maximal Use PK of ARQ-151 in Adolescents/Children With Mild/Moderate Eczema
Official title: An Open Label, Phase 1, Pharmacokinetics, Maximal Usage Pharmacokinetics, Safety, and Efficacy Study of ARQ-151 Cream 0.15% or ARQ-151 Cream 0.05% Administered QD in Adolescent and Pediatric Subjects With Mild to Moderate Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Atopic Dermatitis (Eczema)
Lead sponsor: Arcutis Biotherapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2019-11-07
Enrollment: 101
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a research study where all subjects will receive study medication to understand how the body processes the study medication, and to determine the PK, safety and efficacy of ARQ-151 cream 0.15% or 0.05% in adolescent and pediatric subjects with mild to moderate AD. At entry, subjects in Cohorts 1-3 will have 1.5-35% Body Surface Area involvement (excluding the scalp, palms, soles) and mild or moderate atopic dermatitis (AD) based on vIGA-AD. Cohort 2 and Cohort 3 will be performed in parallel and may commence after results are available from ARQ-151-212, a Phase 2 study evaluating ARQ-151 cream 0.05% and 0.15% administered once a day for 4 weeks in adolescents and adults with mild to moderate AD affecting 1.5% to 35% BSA.

For the maximal usage PK study (Cohorts 4-8), subjects will have BSA involvement (excluding the scalp, palms, soles) of ≥ 35% in subjects 3 months old to 11 years old (inclusive) or ≥25% in subjects 12 to \<17 years old with mild or moderate AD .

Seven groups will be evaluated, including:

* Cohort 1: ARQ-151 cream 0.15% in adolescents (12-17 years old; inclusive)
* Cohort 2: ARQ-151 cream 0.15% in children 6-11 years old (inclusive)
* Cohort 3: ARQ-151 cream 0.15% in children 2-5 years old (inclusive; will be performed in parallel with Cohort 2)
* Cohort 4: ARQ-151 cream 0.15% in adolescents 12 to \<17 years old
* Cohort 5: ARQ-151 cream 0.15% in children 6-11 years old (inclusive)
* Cohort 6: ARQ-151 cream 0.15% in children 2-5 years old (inclusive)
* Cohort 7: ARQ-151 cream 0.05% in children 2-5 years old (inclusive)
* Cohort 8: ARQ-151 cream 0.05% in children 3 months old to less than 2 years old

Subjects will apply ARQ-151 cream 0.15% or 0.05% once a day for 28 days to all AD affected areas and any newly appearing AD lesions that arise during the study, except on the scalp.


Eligibility criteria: Inclusion Criteria:

1. Informed consent of parent(s) or legal guardian, and, if age appropriate, assent by the subject, as required by local laws.
2. Males or females, 12-17 years old (inclusive; Cohort 1), or 6-11 years old (inclusive; Cohort 2), or 2-5 years old (inclusive; Cohort 3), and in the maximal usage PK study subjects aged 12 to \<17 years old (Cohort 4), 6 to 11 years old (Cohort 5), 2-5 years old (Cohort 6 and Cohort 7), or 3 months to less than 2 years old (Cohort 8).
3. Clinical diagnosis of active atopic dermatitis for at least 3 months (2 weeks for Cohort 8).
4. EASI Score ≥5.
5. vIGA-AD score of 'Mild' ('2') or 'Moderate ('3').
6. Has AD involvement of 1.5 to 35% BSA (Cohorts 1-3) or ≥25% BSA (Cohorts 4-7), all excluding the scalp, palms, soles; or for Cohort 8 ≥35% BSA excluding the scalp, perioral, and below wrists/ankles .
7. Females of childbearing potential must have a negative serum pregnancy test at Screening and, if sexually active, agree to use birth control throughout the trial.
8. In good health as judged by the Investigator, based on medical history, physical examination, and clinical tests.

Exclusion Criteria:

1. Subjects with any serious medical or psychiatric condition or clinically significant physical examination or test abnormality that would prevent study participation or place the subject at significant risk.
2. Subjects with unstable AD or any consistent requirement for high potency topical steroids to manage AD signs or symptoms.
3. Subjects who cannot discontinue the use of strong P-450 cytochrome inducers or inhibitors.
4. Subjects who are unwilling to refrain from prolonged sun exposure and from using a tanning bed or other artificial light emitting devices (LEDs) for 4 weeks prior to Baseline/Visit 2 and during the study.
5. Subjects who cannot discontinue systemic and/or topical therapies.
6. 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.
7. Subjects with actively infected AD or any infection that required oral or intravenous administration of antibiotics, antifungal or antiviral agents
8. Known or suspected:

   1. severe renal insufficiency or moderate to severe hepatic disorders (Child-Pugh B or C)
   2. history of chronic infectious disease (e.g., hepatitis B, hepatitis C, or human immunodeficiency virus (HIV))
   3. hypersensitivity to component(s) of the investigational product
   4. history of severe depression, suicidal ideation, Baseline/Screening C-SSRS indicative of suicidal ideation, whether lifetime or recent/current
9. Females who are pregnant, wishing to become pregnant during the study, or are breast-feeding.
10. Subjects (12 to 17 years old, inclusive) with modified PHQ-A score ≥10 at Screening or Baseline visits.
11. Subjects (6 to 11 years old, inclusive) with a CDI-2 (parent report) raw score \>20 at Screening/Baseline
12. Subjects with a history of a major surgery within 4 weeks prior to Baseline/Visit 1 or subjects who have a major surgery planned during the study.
13. Subjects with prior exposure to ARQ-151
14. Subjects 3 to \<12 months old who were premature at birth
15. Subject is nursing and subject's mother requires high dose systemic steroids

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) of roflumilast and its N-oxide metabolite
timeFrame: 4 weeks
measure: Area under the plasma concentration-time curve within a dosing interval (AUC) for roflumilast and its N-oxide metabolite
timeFrame: 4 weeks
measure: Treatment Emergent Adverse Events (TEAE)
timeFrame: 4 weeks
Secondary outcomes:
measure: Eczema Area and Severity Index (EASI) Total Score Change and Percent Change in Total Score
timeFrame: Baseline, Week 2, and Week 4
measure: Eczema Area and Severity Index Score 100%, 90%, 75%, and 50% Improvement (EASI100, EASI90, EASI75, and EASI50)
timeFrame: Baseline, Week 2, and Week 4
measure: Achievement of a Validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA-AD) score of 'clear' or 'almost clear' at each study visit, or 'clear' or 'almost clear' with a 2-point improvement from baseline at each study visit
timeFrame: Baseline, Week 2, Week 4
measure: Change from baseline in vIGA-AD score at each study visit
timeFrame: Baseline, Week 2, Week 4
measure: Body Surface Area (BSA) Involvement Change
timeFrame: Baseline, Week 2, Week 4
measure: Worse Itch Numerical Rating Score (WI-NRS) Pruritis Score Change
timeFrame: Baseline, Week 2, Week 4
measure: WI-NRS Pruritus Score Improvement
timeFrame: Baseline, Week 2, Week 4
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Arcutis Clinical Site 07
state: Alabama
city: Rancho Santa Margarita
country: United States
facility: Arcutis Clinical Site 11
state: California
city: Coral Gables
country: United States
facility: Arcutis Clinical Site 02
state: Florida
city: Hialeah
country: United States
facility: Arcutis Clinical Site 05
state: Florida
city: Miami
country: United States
facility: Arcutis Clinical Site 13
state: Florida
city: Mount Pleasant
country: United States
facility: Arcutis Clinical Site 01
state: South Carolina
city: San Antonio
country: United States
facility: Arcutis Clinical Site 06
state: Texas
city: Orem
country: United States
facility: Arcutis Clinical Site 03
state: Utah
city: West Jordan
country: United States
facility: Arcutis Clinical Site 10
state: Utah
city: Spokane
country: United States
facility: Arcutis Clinical Site 12
state: Washington
Study officials:
affiliation: Arcutis Biotherapeutics, Inc.
name: David Berk, MD
role: STUDY_DIRECTOR
References: