A Study of Baricitinib (LY3009104) in Children From 6 Years to Less Than 18 Years of Age With Alopecia Areata

Study Overview
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Brief Summary
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The main purpose of this study is to determine the efficacy and safety of baricitinib for the treatment of severe or very severe alopecia areata (hair loss) in children from 6 years to less than 18 years of age. The study is divided into 4 periods, a 5-week Screening period, a 36-week Double-Blind Treatment Period, an approximately 2-year Long-term Extension Period, and a 4-week Post-treatment Follow-up period.

Official Title
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A Phase 3, Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics (PK) of Baricitinib in Children From 6 Years to Less Than 18 Years of Age With Alopecia Areata

Conditions
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Areata Alopecia, Alopecia, Hypotrichosis, Hair Diseases, Skin Diseases, Pathological Conditions, Anatomical

Intervention / Treatment
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* Drug: Baricitinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Enrollment will be fully sequential by age group, with adolescents (12 to less than 18 years old) enrolling before children (6 to less than 12 years old). Have severe areata alopecia (AA) for at least 1 year Diagnosis for at least 1 year Current AA episode of at least 6 months' duration SALT score ≥50% at screening and baseline History of trial and failure with at least 1 available treatment (topical or other) for AA History of psychological counseling related to AA Current episode of severe AA of less than 8 years. Note: Participants who have severe AA for ≥8 years may be enrolled if episodes of regrowth, spontaneous or under treatment, have been observed on the affected areas over the past 8 years. Exclusion Criteria: Primarily diffuse type of AA (characterized by diffuse hair shedding). Are currently experiencing other forms of alopecia including, but not limited to trichotillomania, telogen effluvium, chemotherapy-induced hair loss, or any other concomitant conditions (for example, tinea capitis, psoriasis, lupus erythematosus, or secondary syphilis) that would interfere with evaluations of the effect of study medication on AA. Are largely or wholly incapacitated permitting little or no self-care, such as being bedridden Have uncontrolled arterial hypertension Have had major surgery within 8 weeks prior to screening or will require major surgery during the study Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute an unacceptable risk when taking IP or interfere with the interpretation of data. Have a positive test for hepatitis B virus (HBV) infection Have hepatitis C virus (HCV) infection (positive for anti hepatitis C antibody with confirmed presence of HCV ribonucleic acid [RNA]). Have evidence of human immunodeficiency virus (HIV) infection and/or positive HIV antibodies.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Baricitinib High Dose<br>Participants will receive baricitinib high dose orally. | Drug: Baricitinib<br>* Administered orally<br>* Other names: LY3009104;|
| Experimental: Baricitinib Low Dose<br>Participants will receive baricitinib low dose orally. | Drug: Baricitinib<br>* Administered orally<br>* Other names: LY3009104;|
| Placebo Comparator: Placebo<br>Participants will receive placebo | Drug: Placebo<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving an Absolute Severity of Alopecia Tool (SALT) ≤20 |  | Week 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Baseline in SALT Score |  | Baseline, Week 36 | 
| Percentage of Participants Achieving At Least 90% Improvement from Baseline (SALT90) |  | Week 36 | 
| Percentage of Participants Achieving an Absolute SALT ≤10 |  | Week 36 | 
| Percentage of Participants with Patient Reported Outcome (PRO) for Scalp Hair Assessment Score of 0 or 1 Among Participants 12 Years and Older with PRO for Scalp Hair Assessment Score ≥3 at Baseline |  | Week 36 | 
| Mean Change from Baseline in SALT Score |  | Baseline, Week 36 | 
| Percentage of Participants Achieving At Least 50% Improvement from Baseline (SALT50) |  | Week 36 | 
| Percentage of Participants Achieving At Least 75% Improvement from Baseline (SALT75) |  | Week 36 | 
| Percentage of Participants Achieving At Least 100% Improvement from Baseline (SALT100) |  | Week 36 | 
| Percentage of Participants Achieving Clinician-Reported Outcome (ClinRO) Measure for Eyebrow (EB) Hair Loss 0 or 1 Among Participants with CLinRO Measure for EB Hair Loss ≥2 at Baseline |  | Week 36 | 
| Percentage of Participants Achieving ClinRO Measure for Eyelash (EL) Hair Loss 0 or 1 Among Participants with CLinRO Measure for EL Hair Loss ≥2 at Baseline |  | Week 36 | 
| Percentage of Participants Achieving PRO Measure for EB 0 or 1 (Among Participants 12 Years or Older with PRO Measure for EB ≥2 at Baseline) |  | Week 36 | 
| Percentage of Participants Achieving PRO Measure for EL 0 or 1 (Among Participants 12 Years or Older with PRO Measure for EL ≥2 at Baseline) |  | Week 36 | 
| Mean Change from Baseline in Hospital Anxiety Depression Scale (HADS) | The HADS is a participant-rated instrument used to assess both anxiety and depression and is available in a pediatric self-report for participants ≥12 years old. This instrument consists of 14 item questionnaires, each item is rated on a 4-point scale. Scores for each domain (anxiety and depression) can range from 0 to 21, with higher scores indicating greater anxiety or depression. | Week 36 | 
| Mean Change from Baseline in Patient-Reported Outcome Measurement Information System (PROMIS) Anxiety Score | The PROMIS Anxiety Short Form (8 questions, 8a v2.0) is available in a pediatric self-report (ages 8 to <18 years) and for parents/caregivers serving as proxy reporters for their children (youth ages ≥5 years). Both pediatric self-report and proxy-report versions assess anxiety in the past seven days. Response options range from 1 = Never; 2 = Rarely; 3 = Sometimes; 4 = Often; to 5 = Almost always. Total raw scores are converted to T-Scores with higher scores representing greater anxiety. | Baseline, Week 36 | 
| Mean Change from Baseline in PROMIS Depression Score | The PROMIS Depression Short Form (8a v2.0 and 6a v2.0) is available in a pediatric self-report (ages 8 to <18 years) and for parents/caregivers serving as proxy reporters for their children (youth ages ≥5 years). Both pediatric self-report and proxy-report versions assess depression in the past seven days. Response options range from 1 = Never; 2 = Rarely; 3 = Sometimes; 4 = Often; to 5 = Almost always. Total raw scores are converted to T-Scores with higher scores representing greater depression. | Baseline, Week 36 | 
| Mean Change from Baseline in PROMIS Peer Relationship Score | The PROMIS Peer Relationships Short Form planned to be used in the study measures 2 aspects of social functioning, friendship quality and peer acceptance, and is available in a pediatric self-report (ages 8 to <18 years) and for parents/caregivers serving as proxy reporters for their children (youth ages 5 to <8 years). | Baseline, Week 36 | 
| Mean Change from Baseline in Family Dermatology Life Quality Index (FDLQI) | The FDLQI is a 10-item validated questionnaire designed for adult (>16 years old) family members of participants. The questionnaire is completed by family members of the AA participants (for example, parents/caregivers) and measures the secondary impact of the participant's skin disease on family QoL. Response categories include not at all/not relevant, only a little, quite a lot, and very much, with corresponding scores of 0, 1, 2, and 3, respectively, with unanswered (not relevant) responses scored as 0. | Baseline, Week 36 | 
| Pharmacokinetics (PK): Maximum Concentration (Cmax) |  | Baseline through Week 36 | 
| PK: Area Under the Concentration Curve (AUC) |  | Baseline through Week 36 | 
| Change of Immunoglobulin G (IgG) Titers |  | Pre-Vaccination to 4 Weeks and 12 Weeks Post-Vaccination |