A Study to Learn About the Study Medicine (Called Ritlecitinib) For the Potential Treatment of Severe Alopecia Areata (AA) In Children 6 To Less Than 12 Years of Age

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the pharmacokinetics (how the medicine is changed and eliminated from your body after you take it) and pharmacodynamics (effects of the medicine in the body) of the study medicine (called Ritlecitinib) in children of 6 to <12 years of age with Alopecia Areata, a condition of scalp hair loss. 12 children with alopecia areata will be participating in this study. All participants will receive study medicine with a dose of 20 milligram (mg) orally once daily for 7 days. 5 blood samples will be collected on day 7 for pharmacokinetic evaluation and 2 blood samples each at screening and on Day 7 will be collected for pharmacodynamic evaluation. Participants will take part in the study for about 10 weeks.

Detailed Description
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This is an interventional, Pharmacokinetic (PK), Pharmacodynamic (PD), phase 1, open label study in children 6 to less than 12 years of age with ≥50% scalp hair loss due to severe alopecia areata. The purpose of the study is to collect data to support dose selection for subsequent studies in the same population. Participants will be screened and, if all eligibility criteria are met, will receive the first dose of Investigational product within 28 days after the screening visit. Participants will receive 20 mg ritlecitinib in one dose, daily, for 7 consecutive days. Blood samples for pharmacodynamic evaluation will be collected on screening and Day 7. Blood samples for pharmacokinetic evaluation will be collected on Day 7 at: 0 hr (pre-dose), 0.5 hr, 1 hr, 3 hrs, and 8 hrs after dosing. At least 12 evaluable participants with respect to the primary endpoint will be enrolled in the study. Participants and their parents/legal guardians will be required to visit the study site 3 times during the study (Screening, Day 1 and Day 7) A safety follow-up visit will be conducted by phone, 28 to 35 days after the last dose of ritlecitinib.

Official Title
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AN INTERVENTIONAL PK, PD, PHASE 1, OPEN-LABEL STUDY TO INVESTIGATE PK AND PD OF MULTIPLE-DOSE RITLECITINIB IN CHILDREN 6 TO LESS THAN 12 YEARS OF AGE WITH SEVERE ALOPECIA AREATA

Conditions
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Alopecia Areata

Intervention / Treatment
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* Drug: Ritlecitinib 20 mg


Participation Criteria
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Eligibility Criteria
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Key Inclusion criteria: Participants who are 6 to less than12 years old at the baseline visit. A diagnosis of severe AA, including AT and AU, with ≥50% scalp hair loss due to AA (ie, a SALT score of ≥50) at both the Screening and Baseline visits, without evidence of terminal hair regrowth within the previous 12 months. Key Exclusion Criteria: A known congenital cause of AA, other systemic diseases that may cause hair loss (eg, lupus erythematosus, thyroiditis, systemic sclerosis, lichen planus, etc) or other etiology of hair loss (eg, telogen effluvium, androgenetic alopecia, etc). Any present malignancies or history of malignancies, history of any lymphoproliferative disorder History (one or more episodes) of CMV, varicella, herpes zoster (shingles) or disseminated herpes simplex. Other medical or psychiatric condition (including recent [within the past year] or active suicidal ideation/behavior) that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. Not up to date with all age appropriate vaccines (including 2-dose vaccination for varicella) or vaccination with attenuated live vaccine within 6 weeks of first dose of study medicine.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 11 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: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ritlecitinib 20 mg<br>Participants will receive Ritlecitinib 20 mg by mouth once daily (QD). | Drug: Ritlecitinib 20 mg<br>* orally administered, Ritlecitinib 20 mg once daily (QD)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration time profile over the dosing interval 24 hrs, at steady-state (AUC24) on Day 7 | AUC is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption. | 0 (pre-dose), 0.5, 1, 3 and 8 hours post-dose on Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) | Maximum Observed Plasma Concentration | 0 (pre-dose), 0.5, 1, 3 and 8 hours post-dose on Day 7 | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Time to Reach Maximum Observed Plasma Concentration | 0 (pre-dose), 0.5, 1, 3 and 8 hours post-dose on Day 7 | 
| Apparent Oral Clearance (CL/F) | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. | Day 7 | 
| Apparent Volume of Distribution (Vz/F) | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | 0 (pre-dose), 0.5, 1, 3 and 8 hours post-dose on Day 7 | 
| Terminal elimination Half-Life (t1/2) | Terminal elimination half-life. | 0 (pre-dose), 0.5, 1, 3 and 8 hours post-dose on Day 7 | 
| Change from baseline in interferon gamma, IP-10 and lymphocyte subsets (T cell, B cell, and NK cells) | Change from baseline in interferon gamma, IP-10 and lymphocyte subsets (T cell, B cell, and NK cells) | Day 7 | 
| Incidence of treatment emergent adverse event (TEAE) | To evaluate the safety and tolerability of ritlecitinib in children with alopecia areata 6 to less than 12 years of age. | Baseline through Week 5 (Day 35) | 
| Incidence of Treatment related AEs | To evaluate the safety and tolerability of ritlecitinib in children with alopecia areata 6 to less than 12 years of age. | Baseline through week 5 (Day 35) | 
| Incidence of Serious AEs (SAEs) | To evaluate the safety and tolerability of ritlecitinib in children with alopecia areata 6 to less than 12 years of age. | Baseline through week 5 (Day 35) | 
| Incidence of AEs leading to discontinuation | To evaluate the safety and tolerability of ritlecitinib in children with alopecia areata 6 to less than 12 years of age. | Baseline through Day 7 | 
| Clinically significant abnormalities in vital signs | To evaluate the safety and tolerability of ritlecitinib in children with alopecia areata 6 to less than 12 years of age. | Baseline through Day 7 | 
| Clinically significant abnormalities in clinical laboratory values | To evaluate the safety and tolerability of ritlecitinib in children with alopecia areata 6 to less than 12 years of age. | Baseline through Day 7 | 
| For overall taste, percent of participants reporting likeability on the scale from 1-5 will be reported | Overall taste assesses the degree that a participant likes or dislikes a drug formulation based on sensory attributes experienced by the participant after tasting a product. It is scored based on a measurement of taste questionnaire. | Day 1 and 7 | 
| For overall mouthfeel, percent of participants reporting how the medicine felt on the scale from 1-5 will be reported. | Mouth feel assesses the degree that a participant experienced this sensory attribute after tasting a drug formulation. It is scored based on a measurement of taste questionnaire | Day 1 and 7 | 
| For overall volume, percent of participants reporting likeability of the amount of medicine taken on the scale from 1-5 will be reported. | Volume assesses the participant experience on the amount of medicine taken. It is scored based on taste assessment questionnaire | Day 1 and 7 |