Dupilumab in the Treatment of Pediatric Alopecia Areata

Study Overview
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Brief Summary
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This is a prospective, randomized, double-blind, placebo-controlled clinical trial. The study will take place at four sites. This trial will enroll a total of 76 children and adolescent subjects with moderate to severe AA (affecting more than 50% of the scalp) at the time of screening with a targeted 60 subjects completing through Week 48. All subjects must have evidence of hair regrowth within the last 7 years of their last episode of hair loss; and have screening IgE ≥200 and/or have personal and/or familial history of atopy. Study participation will be up to 116 weeks, consisting of: a screening period of up to 4 weeks; a 48-week placebo-controlled period; a 48-week open-label extension period; followed by a 16-week follow-up period.

Detailed Description
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After providing consent, subjects will be assessed for study eligibility during the screening period (within 4 weeks of Baseline), which includes a review of past and current medical conditions, detailed review of past and current medications, a physical examination, clinical assessments, and laboratory tests for safety. Subjects who meet inclusion and exclusion criteria for eligibility will undergo Baseline assessments at Week 0. Subjects will return for visits every 8-16 weeks for repeat clinical assessments, medication reviews, and monitoring for adverse events. Female subjects will undergo a urine pregnancy test (where applicable) at each of these visits.

Official Title
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Dupilumab in the Treatment of Pediatric Alopecia Areata

Conditions
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Alopecia Areata

Intervention / Treatment
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* Drug: Dupilumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects who are at least 6 years old and under 18 years old, who can provide assent (if appropriate), and for whom signed informed consent can be provided by parent or legal guardian prior to participation in any study assessments or procedures Subject ≥ 30 kg. Subject is able to adhere to the study visit schedule and other protocol requirements. Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. While on investigational product and for at least 28 days after taking the last dose of investigational product (IP), FCBP who engage in activity in which conception is possible must use one of the approved contraceptive options described below: Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner's vasectomy; OR Option 2: Male or female condom (latex condom or non-latex condom NOT made out of natural [animal] membrane [for example, polyurethane]); PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide. Subject has a history of at least 6 months of moderate to severe AA (≥ 50% scalp involvement) as measured using the SALT score. Subject has a screening IgE ≥ 200 and/or personal and/or familial history of atopy (including asthma, atopic dermatitis, allergic rhinitis, food allergy, or eosinophilic esophagitis in the participant or a first degree relative). Subject is judged to be in otherwise good overall health following a detailed medical and medication history, physical examination, and laboratory testing. Exclusion Criteria: Inability or unwillingness of a participant to give written informed consent or comply with study protocol Subject is pregnant or breastfeeding. Subject's cause of hair loss is indeterminable and/or they have concomitant causes of alopecia, such traction, cicatricial, pregnancy-related, drug-induced, telogen effluvium, or advanced androgenetic alopecia (i.e. Ludwig Type III or Norwood-Hamilton Stage ≥ V). Subject has a history of AA with no evidence of hair regrowth for ≥ 7 years since their last episode of hair loss. Severe, uncontrolled asthma or a history of life-threatening asthma exacerbations while on appropriate anti-asthmatic mediations. Subject has an active bacterial, viral, or helminth parasitic infections; OR a history of ongoing, recurrent severe infections requiring systemic antibiotics Subject with a known or suspected underlying immunodeficiency or immune-compromised state as determined by the investigator. Subject has a concurrent or recent history of severe, progressive, or uncontrolled renal, hepatic, hematological, intestinal, metabolic, endocrine, pulmonary, cardiovascular, or neurological disease. Known active hepatitis B, hepatitis C, human immunodeficiency virus (HIV), or positive HIV serology at the time of screening for subjects determined by the investigators to be at high-risk for this disease. Subject has a suspected or active lymphoproliferative disorder or malignancy; OR a history of malignancy within 5 years before the Baseline assessment, except for completely treated in situ non-melanoma skin and cervical cancers without evidence of metastasis. Subject has received a live attenuated vaccine ≤ 30 days prior to study randomization. Subject has any uncertain or clinically significant laboratory abnormalities that may affect interpretation of study data or endpoints. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study. History of adverse systemic or allergic reactions to any component of the study drug. Use of systemic immunosuppressive medications, including, but not limited to, cyclosporine, systemic or intralesional corticosteroids, mycophenolate mofetil, azathioprine, methotrexate, tacrolimus, or ultraviolet (UV) phototherapy with/without Psoralen Ultraviolet A (PUVA) therapy within 4 weeks prior to randomization. Use of an oral JAK inhibitor (tofacitinib, ruxolitinib, baricitinib, or investigational oral JAK Inhibitors) within 12 weeks prior to the Baseline visit. Subject has been previously treated with dupilumab for more than 3 months Subject has used topical corticosteroids, and/or tacrolimus, and/or pimecrolimus within 1 week before the Baseline visit. Subject currently uses or plans to use anti-retroviral therapy at any time during the study.

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: Dupilumab<br>every other week 200 mg or 300 mg (weight-based) SC injections | Drug: Dupilumab<br>* every other week 200 mg or 300 mg (weight-based) SC injections<br>* Other names: Dupixent;|
| Placebo Comparator: Placebo<br>Tablets without active ingredients | Drug: Placebo<br>* Placebo comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Severity of Alopecia Tool (SALT) score | Change in the SALT score from baseline compared to Week 48 in Dupilumab treated vs placebo treated subjects. SALT score is the sum of percentage of hair loss in all areas (higher score indicates greater hair loss). The SALT is a validated instrument for measuring the amount of scalp hair loss at a single point in time The SALT is a validated instrument for measuring the amount of scalp hair loss at a single point in time SALT - Scalp divided into four areas: vertex (40% of scalp surface area), right profile (18% of scalp surface area), left profile (18% of scalp surface area), and posterior scalp (24% of scalp surface area). Percentage of hair loss in these areas is multiplied by percent surface area of the scalp in that area. SALT score is the sum of percentage of hair loss in all areas. SALT scores range from 0 (no hair loss) to 100 (complete scalp hair loss) with lower score indicating better health outcomes/less hair loss. | Baseline and Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in SALT score in each treatment group at 48 compares to baseline | The SALT is a validated instrument for measuring the amount of scalp hair loss at a single point in time. The scalp is divided into four areas: vertex (40% of scalp surface area), right profile (18% of scalp surface area), left profile (18% of scalp surface area), and posterior scalp (24% of scalp surface area). The percentage of hair loss in these areas is multiplied by the percent surface area of the scalp in that area. The SALT score is the sum of the percentage of hair loss in all areas. The SALT score ranges from 0 (no hair loss) to 100 (complete scalp hair loss), with a lower score indicating better health outcomes/less hair loss. | Baseline and Week 48 | 
| Change in SALT score in each treatment group at Week 96 compared to baseline | The SALT is a validated instrument for measuring the amount of scalp hair loss at a single point in time. The scalp is divided into four areas: vertex (40% of scalp surface area), right profile (18% of scalp surface area), left profile (18% of scalp surface area), and posterior scalp (24% of scalp surface area). The percentage of hair loss in these areas is multiplied by the percent surface area of the scalp in that area. The SALT score is the sum of the percentage of hair loss in all areas. The SALT score ranges from 0 (no hair loss) to 100 (complete scalp hair loss), with a lower score indicating better health outcomes/less hair loss. | Baseline and Week 96 | 
| Proportion of subjects achieving an absolute SALT score of ≤ 20 at Week 48 in dupilumab vs. placebo-treated subjects | The SALT is a validated instrument for measuring the amount of scalp hair loss at a single point in time. The scalp is divided into four areas: vertex (40% of scalp surface area), right profile (18% of scalp surface area), left profile (18% of scalp surface area), and posterior scalp (24% of scalp surface area). The percentage of hair loss in these areas is multiplied by the percent surface area of the scalp in that area. The SALT score is the sum of the percentage of hair loss in all areas. The SALT score ranges from 0 (no hair loss) to 100 (complete scalp hair loss), with a lower score indicating better health outcomes/less hair loss. | Week 48 | 
| Proportion of subjects achieving an absolute SALT score of ≤ 20 at Week 48 in each treatment group | The SALT is a validated instrument for measuring the amount of scalp hair loss at a single point in time. The scalp is divided into four areas: vertex (40% of scalp surface area), right profile (18% of scalp surface area), left profile (18% of scalp surface area), and posterior scalp (24% of scalp surface area). The percentage of hair loss in these areas is multiplied by the percent surface area of the scalp in that area. The SALT score is the sum of the percentage of hair loss in all areas. The SALT score ranges from 0 (no hair loss) to 100 (complete scalp hair loss), with a lower score indicating better health outcomes/less hair loss. | Week 48 | 
| Proportion of subjects achieving an absolute SALT score of ≤ 20 at Week 96 in each treatment group | The SALT is a validated instrument for measuring the amount of scalp hair loss at a single point in time. The scalp is divided into four areas: vertex (40% of scalp surface area), right profile (18% of scalp surface area), left profile (18% of scalp surface area), and posterior scalp (24% of scalp surface area). The percentage of hair loss in these areas is multiplied by the percent surface area of the scalp in that area. The SALT score is the sum of the percentage of hair loss in all areas. The SALT score ranges from 0 (no hair loss) to 100 (complete scalp hair loss), with a lower score indicating better health outcomes/less hair loss. | Week 96 | 
| Proportion of subjects achieving Improvement in SALT score at Week 48 in dupilumab vs placebo-treated subjects | The SALT is a validated instrument for measuring the amount of scalp hair loss at a single point in time The SALT is a validated instrument for measuring the amount of scalp hair loss at a single point in time SALT - Scalp divided into four areas: vertex (40% of scalp surface area), right profile (18% of scalp surface area), left profile (18% of scalp surface area), and posterior scalp (24% of scalp surface area). Percentage of hair loss in these areas is multiplied by percent surface area of the scalp in that area. SALT score is the sum of percentage of hair loss in all areas. SALT scores range from 0 (no hair loss) to 100 (complete scalp hair loss) with lower score indicating better health outcomes/less hair loss. The proportion of subjects achieving at least 30%/50%/75%/90% improvement in Severity of Alopecia Tool (SALT) score (SALT-30/50/75/90) at Week 48 in dupilumab compared to placebo. | Week 48 | 
| Proportion of subjects achieving Improvement in SALT score at Week 48 in each treatment group | Proportion of subjects achieving Improvement in SALT score. The SALT is a validated instrument for measuring the amount of scalp hair loss at a single point in time The SALT is a validated instrument for measuring the amount of scalp hair loss at a single point in time SALT - Scalp divided into four areas: vertex (40% of scalp surface area), right profile (18% of scalp surface area), left profile (18% of scalp surface area), and posterior scalp (24% of scalp surface area). Percentage of hair loss in these areas is multiplied by percent surface area of the scalp in that area. SALT score is the sum of percentage of hair loss in all areas. SALT scores range from 0 (no hair loss) to 100 (complete scalp hair loss) with lower score indicating better health outcomes/less hair loss. The proportion of subjects achieving at least 30%/50%/75%/90% improvement in Severity of Alopecia Tool (SALT) score (SALT-30/50/75/90) at Week 48 in each treatment group. | Week 48 | 
| Proportion of subjects achieving Improvement in SALT score at 96 in each treatment group | Proportion of subjects achieving Improvement in SALT score. The SALT is a validated instrument for measuring the amount of scalp hair loss at a single point in time The SALT is a validated instrument for measuring the amount of scalp hair loss at a single point in time SALT - Scalp divided into four areas: vertex (40% of scalp surface area), right profile (18% of scalp surface area), left profile (18% of scalp surface area), and posterior scalp (24% of scalp surface area). Percentage of hair loss in these areas is multiplied by percent surface area of the scalp in that area. SALT score is the sum of percentage of hair loss in all areas. SALT scores range from 0 (no hair loss) to 100 (complete scalp hair loss) with lower score indicating better health outcomes/less hair loss. The proportion of subjects achieving at least 30%/50%/75%/90% improvement in Severity of Alopecia Tool (SALT) score (SALT-30/50/75/90) at Week 48 in each treatment group. | Week 96 | 
| Change in the Alopecia Areata Symptom Impact Scale (AASIS) at Week 48 in dupilumab vs placebo-treated | The AASIS is a 13-item, disease specific measure that asks patients with AA about the severity of their symptoms and how these symptoms interfere with their daily functioning. The AASIS uses a 0-10 numeric rating scale that patients find simple to understand and that is easily translated into different languages. AASIS scale 0-10: 0 indicates the symptom was not present and 10 indicates the symptom was as bad as one can imagine, where higher scores indicate worse symptoms. | Baseline and Week 48 | 
| Change in the Alopecia Areata Symptom Impact Scale (AASIS) at Week 48 in each treatment group | The AASIS is a 13-item, disease specific measure that asks patients with AA about the severity of their symptoms and how these symptoms interfere with their daily functioning. The AASIS uses a 0-10 numeric rating scale that patients find simple to understand and that is easily translated into different languages. AASIS scale 0-10: 0 indicates the symptom was not present and 10 indicates the symptom was as bad as one can imagine, where higher scores indicate worse symptoms. | Baseline and Week 48 | 
| Change in the Alopecia Areata Symptom Impact Scale (AASIS) at Week 96 in each treatment group | The AASIS is a 13-item, disease specific measure that asks patients with AA about the severity of their symptoms and how these symptoms interfere with their daily functioning. The AASIS uses a 0-10 numeric rating scale that patients find simple to understand and that is easily translated into different languages. AASIS scale 0-10: 0 indicates the symptom was not present and 10 indicates the symptom was as bad as one can imagine, where higher scores indicate worse symptoms. | Baseline and Week 96 | 
| Patient's Global Impression of Change (PGIC) Scale score at Week 48 in dupilumab vs. placebo-treated subjects | PGIC is a self-administered questionnaire evaluating improvement or worsening of the participant's alopecia areata as compared to the start of the study and uses a single item, Since the start of the study, my alopecia areata has…, with 7 responses ranging from 0 no change or worse to 7 a great deal better where higher scores indicate greater improvement. | Week 48 | 
| Patient's Global Impression of Change (PGIC) Scale score at Week 48 in each treatment group | PGIC is a self-administered questionnaire evaluating improvement or worsening of the participant's alopecia areata as compared to the start of the study and uses a single item, Since the start of the study, my alopecia areata has…, with 7 responses ranging from 0 no change or worse to 7 a great deal better where higher scores indicate greater improvement. | Week 48 | 
| Patient's Global Impression of Change (PGIC) Scale score at Week 96 in each treatment group | PGIC is a self-administered questionnaire evaluating improvement or worsening of the participant's alopecia areata as compared to the start of the study and uses a single item, Since the start of the study, my alopecia areata has…, with 7 responses ranging from 0 no change or worse to 7 a great deal better where higher scores indicate greater improvement. | Week 96 | 
| Proportion of subjects achieving Alopecia Areata Physician's Global Assessment (aaPGA) = 0-1 at Week 48 in dupilumab vs placebo-treated subjects | The proportion of alopecia areata subjects with aaPGA score of 0 or 1 at Week 48. The aaPGA is used to assess the clinical response to treatment based on a 6-point scale ranging from 0 (no regrowth) to 5 (100% regrowth), where higher scores indicate greater hair regrowth. | Week 48 | 
| Proportion of subjects achieving Alopecia Areata Physician's Global Assessment (aaPGA) = 0-1 at Week 48 in each treatment group | The proportion of alopecia areata subjects with aaPGA score of 0 or 1 at Week 48. The aaPGA is used to assess the clinical response to treatment based on a 6-point scale ranging from 0 (no regrowth) to 5 (100% regrowth), where higher scores indicate greater hair regrowth. | Week 48 | 
| Proportion of subjects achieving Alopecia Areata Physician's Global Assessment (aaPGA) = 0-1 at Week 96 in each treatment group | The proportion of alopecia areata subjects with aaPGA score of 0 or 1 at Week 96. The aaPGA is used to assess the clinical response to treatment based on a 6-point scale ranging from 0 (no regrowth) to 5 (100% regrowth), where higher scores indicate greater hair regrowth. | Week 96 | 
| Number of adverse events reported | Number of adverse events reported throughout the study. The adverse event will be described and categorized as treatment emergent, serious, abnormal in vital signs, and abnormal in lab parameters. | Week 96 |