Dupilumab in the Treatment of Pediatric Alopecia Areata

Обзор

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 adolescents with moderate to severe AA (affecting at least 30% of the scalp) at the time of screening with a targeted 61 participants 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 124 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 24-week follow-up period.

Подробное описание

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.

Вмешательства

• Препарат Dupilumab
  Participants weighing 15 kg \< 30 kg = 300 mg Every 4 Weeks; Participants weighing 30 kg \< 60 kg = 200 mg Every 2 Weeks; Participants weighing ≥ 60 kg = 300 mg Every 2 Weeks;
• Препарат Placebo
  Participants weighing 15 kg \< 30 kg Every 4 Weeks; Participants weighing 30 kg \< 60 kg Every 2 Weeks; Participants weighing ≥ 60 kg Every 2 Weeks

Первичные конечные точки

• Change in the Severity of Alopecia Tool (SALT) score [Срок оценки: Baseline and Week 48]

Вторичные конечные точки (12)

• Proportion of participants achieving an absolute SALT score of ≤ 20 at Week 48 in dupilumab vs. placebo-treated participants [Срок оценки: Baseline and Week 48]
• Change in SALT score in each treatment group at Weeks 48 and 96 compared to baseline [Срок оценки: Baseline Week 48 and Week 96]
• Proportion of subjects achieving an absolute SALT score of ≤ 20 at Week 48 and Week 96 in each treatment group [Срок оценки: Weeks 48 and 96]
• Proportion of participants achieving at least 30%/50%/75%/90% improvement (SALT 30/50/75/90) at Week 48 in dupilumab vs. placebo-treated participants [Срок оценки: Week 48]
• Proportion of participants achieving at least 30%/50%/75%/90% improvement (SALT 30/50/75/90) at Weeks 48 and 96 in each treatment group [Срок оценки: Weeks 48 and 96]
• Change in Alopecia Areata Symptom Impact Scale (AASIS) from Week 0/Baseline at Week 48 in dupilumab vs. placebo-treated participants [Срок оценки: Week 48]
• Change in Alopecia Areata Symptom Impact Scale (AASIS) from Week 0/Baseline at Weeks 48 and 96 in each treatment group [Срок оценки: Weeks 48 and 96]
• Patient's Global Impression of Change (PGIC) Scale score at Week 48 in dupilumab vs. placebo-treated subjects [Срок оценки: Week 48]
• Patient's Global Impression of Change (PGIC) Scale score at Week 48 and 96 in each treatment group [Срок оценки: Weeks 48 and 96]
• Proportion of subjects achieving Alopecia Areata Physician's Global Assessment (aaPGA) = 0-1 at Week 48 in dupilumab vs placebo-treated subjects [Срок оценки: Week 48]
• Proportion of subjects achieving Alopecia Areata Physician's Global Assessment (aaPGA) = 0-1 at Week 48 and 96 in each treatment group [Срок оценки: Weeks 48 and 96]
• Number of adverse events reported [Срок оценки: Week 96]

Критерии участия

Критерии включения

• Male or female participants 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

\-- Participant 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 \[for example, polyurethane\]);
• Participant has a history of at least 6 months of moderate to severe AA (≥ 50% scalp involvement) as measured using the SALT score.
• Participant 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)
• Participant is judged to be in otherwise good overall health following a detailed medical and medication history, physical examination, and laboratory testing.

Критерии исключения

• Inability or unwillingness of a participant to give written informed consent or comply with study protocol
• Participant is pregnant or breastfeeding.
• Participant'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).
• Participant has a history of AA with no evidence of hair regrowth for ≥ 7 years since their last episode of hair loss.
• Severe, uncontrolled asthma (having 2 or exacerbations in the last 12 months that require systemic steroids and/or hospitalization) or a history of life-threatening asthma exacerbations while on appropriate anti-asthmatic medications.
• Participant has an active bacterial, viral, or helminth parasitic infections; OR a history of ongoing, recurrent severe infections requiring systemic antibiotics
• Participant with a known or suspected underlying immunodeficiency or immune-compromised state as determined by the investigator.
• Participant 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.
• Participant 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.
• Participant has received a live attenuated vaccine ≤ 28 days prior to study randomization.
• 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, oral JAK inhibitor (tofacitinib, ruxolitinib, baricitinib, ritlecitinib, or investigational oral JAK Inhibitors) or ultraviolet (UV) phototherapy with/without Psoralen Ultraviolet A (PUVA) therapy, within 4 weeks prior to the Week 0/Baseline visit
• Participant has been previously treated with dupilumab
• Participant has used topical corticosteroids, and/or tacrolimus, and/or pimecrolimus within 1 week before the Baseline visit.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 5 центров

• University of California, Irvine — Irvine
• University of California San Diego — San Diego
• Ann & Robert H. Lurie Children's Hospital of Chicago — Chicago
• Northwestern University Feinberg School of Medicine — Chicago
• Icahn School of Medicine at Mount Sinai — New York

Идентификаторы

NCT: NCT05866562 · 23-00744

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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