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.

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