A Long-term Study of the Medicine Called Abrocitinib in Children Aged 2 Years and Older With Moderate to Severe Eczema

Официальное название

A Phase 3, Multicenter, Long-Term, Open Label Study Evaluating the Safety and Efficacy of Abrocitinib, With or Without Topical Medications Administered to Pediatric Participants Aged 2 Years and Older With Moderate-to-Severe Atopic Dermatitis

Обзор

This 24-month study will assess the long-term safety and efficacy of liquid abrocitinib oral suspension with or without topical medications in children 2 years of age or older with moderate-to-severe atopic dermatitis. The study will enroll two groups: participants who have completed other abrocitinib studies and participants who have never participated in abrocitinib studies.

Подробное описание

Phase 3, open-label study to assess the long-term safety and efficacy of liquid abrocitinib oral suspension with or without topical medications in children ≥2 years of age with moderate-to-severe atopic dermatitis (AD). This study will enroll participants in two cohorts: an extension cohort of participants who previously completed prior abrocitinib studies, and a de novo cohort of participants (6 to \<12 years of age) who have not participated in previous abrocitinib studies. Study duration will be up to 2 years (or commercial availability, whichever occurs earlier). The study will enroll a maximum of approximately 500 participants with moderate-to-severe Atopic Dermatitis from study sites globally (extension cohort will enroll up to 320 participants; de novo cohort will enroll approximately 180 participants). All participants will receive the study intervention abrocitinib oral suspension.

Вмешательства

• Препарат Abrocitinib
  Abrocitinib administered as liquid oral suspension.

Первичные конечные точки

• Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and adverse events (AEs) that lead to study discontinuation [Срок оценки: 0-24 months]

Вторичные конечные точки (12)

• Number of Participants With Clinically Significant Laboratory Abnormalities [Срок оценки: 0-24 months]
• Response based on achieving Validated Investigator's Global Assessment (vIGA) score of clear (0) or almost clear (1) (on a 5-point scale) and a 2 -point reduction from baseline at all scheduled time points [Срок оценки: Baseline, 24 months]
• Percentage of Response based on achieving a ≥4 point improvement from baseline in the Worst Itch Numerical Rating Scale (WI-NRS) at all scheduled time points in participants aged ≥2 to <6 years [Срок оценки: 0-24 months]
• Percentage of Response based on achieving a ≥4-point improvement from baseline in the WSI-NRS at all scheduled time points in participants aged ≥6 to 12 years [Срок оценки: 0-24 months]
• Percentage of Responders based on achieving Eczema Area and Severity Index (EASI)-50, EASI-90 and EASI-100 at all scheduled time points in participants with moderate-to-severe disease treated with abrocitinib [Срок оценки: 0-24 months]
• Percent Change from Baseline (CFB) in EASI total score at all scheduled time points. [Срок оценки: 0-24 months]
• Percentage of Participants with Flares [Срок оценки: 0-24 months]
• CFB in the percentage Body Surface Area (BSA) affected at all scheduled time points [Срок оценки: 0-24 months]
• CFB in Children's Dermatology Life Quality Index (CDLQI) at all scheduled time points. [Срок оценки: 0-24 months]
• CFB in in Infants' Dermatitis Quality of Life (IDQOL) Index at all scheduled time points [Срок оценки: 0-24 months]
• CFB in Patient-Oriented Eczema Measure (POEM) at all scheduled time points [Срок оценки: 0-24 months]
• CFB in Dermatitis Family Impact (DFI) at all scheduled time points [Срок оценки: 0-24 months]

Критерии участия

Inclusion Criteria for the Extension Cohort:

1\. Participants who have completed the treatment phase of the qualifying parent study (age 2 to <12 years old).

• No contraception methods are required for male participants. Female participants must not be pregnant or breastfeeding and, if the participant is of child-bearing potential, must use a highly effective form of contraception (i.e., abstinence) during the study intervention period and for at least 28 days after the last dose of study intervention.

Inclusion Criteria for the De Novo Cohort:

Age

• Children aged 6 to <12 years at the time of informed consent/assent.

• No contraception methods are required for male participants.

Disease Characteristics:

• Participants who meet all of the following AD criteria:

• A documented diagnosis of chronic AD for at least 6 months prior to screening and confirmed at screening and baseline visits according to the Hanifin and Rajka criteria; and
• A diagnosis of moderate-to-severe AD at the baseline visit (must fulfill all of the following criteria: BSA ≥10%, vIGA ≥3, EASI ≥16, and WI-NRS ≥4); and
• Documented history (within 6 months of the screening visit) of inadequate response to treatment with topical medical therapy for AD (eg, TCS and TCI), for at least 4 weeks and are candidates for systemic therapy.

Other Inclusion Criteria:

• Body weight ≥15 kg

Exclusion Criteria for the Extension Cohort:

Medical Conditions:

• Any medical or psychiatric condition including any active suicidal ideation in the past year or suicidal behavior in the past 5 years or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.

If the participant has SDQ total score ≥17, the investigator should exclude the child or refer them to a pediatric MHP to determine if it is safe to participate in the study. A copy or summary of the evaluation should be placed in the site source documents.

Prior/Concomitant Therapy:

• Required use of any prohibited concomitant treatments outlined in Section 6.9.3 and Appendix 9 of study protocol.
• Required vaccination with live attenuated vaccines during study treatment and for 6 weeks after discontinuing study treatment.

Diagnostic Assessments:

• Ongoing adverse event in the parent studies which in the opinion of the investigator, or sponsor, is an ongoing safety concern OR the participant is currently triggering safety monitoring criteria.
• Discontinued from treatment early in the parent studies OR triggered a discontinuation criterion at any point during the parent studies OR meets exclusion criteria from the parent studies which in the opinion of the investigator, or sponsor, is an ongoing safety concern.

Exclusion Criteria for the De Novo Cohort

Medical Conditions:

• Any medical or psychiatric condition including any active suicidal ideation in the past year or suicidal behavior in the past 5 years or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.

If the participant has SDQ total score ≥17, the investigator should exclude them or refer the child to a pediatric MHP to determine if it is safe to participate in the study. A copy or summary of the evaluation should be placed in the site source documents.

• Have any of the following medical conditions:

• Infections:

• Skin infections that require treatment with systemic antimicrobials within 2 weeks prior to Day 1 (baseline) or have superficial skin infections within 1 week of Day 1.
• History of systemic infection requiring hospitalization or parenteral antimicrobial therapy or as otherwise judged clinically significant by the investigator within 1 month prior to Day 1.
• Have a history (single episode) of disseminated herpes zoster or disseminated herpes simplex, or a recurrent localized, dermatomal herpes zoster.
• Infection with HIV, hepatitis B, and/or hepatitis C
• Evidence of active TB or inadequately treated latent TB.
• Skin Conditions:

\- Including but not limited to psoriasis, seborrheic dermatitis or lupus on Day 1 that would interfere with evaluation of AD or response to treatment.

• Other Conditions:

• Documented history of skeletal dysplasia.
• Documented history of retinal detachment.
• History of or conditions associated with thrombocytopenia, coagulopathy or platelet dysfunction.
• Prior history of leukemia, lymphoma, sarcoma or any other malignancy.
• Immunodeficiency disorder or a first-degree relative with a hereditary immunodeficiency.
• Any other medical conditions that in the investigator's judgment make the participant inappropriate for the study.

Prior/Concomitant Therapy:

• Prior treatment with a systemic JAK inhibitor for AD.
• Live attenuated vaccination within 6 weeks prior to Day 1 or require vaccination with live attenuated vaccines during treatment or within 6 weeks after the last dose of study intervention.
• Concomitant use of strong inhibitors and inducers of CYP2C19 enzymes and strong inducers of CYP2C9 enzymes is not allowed in the study.

Prior/Concurrent Clinical Study Experience:

• Previous administration of an investigational drug within 30 days or 5 half lives, whichever is longer, of Day 1.

Diagnostic Assessments:

• Hepatic and/or renal and/or hematological abnormalities defined as:

• AST >2 x ULN
• Hemoglobin <10 g/dL
• ALT >2 x ULN
• ANC <1000/mm3
• Total bilirubin ≥1.5 x ULN
• ALC <500/mm3
• eGFR <60 mL/min/1.73 m2
• Platelets <150,000 /mm3

Other Exclusion Criteria:

• Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 9 центров

• Cahaba Dermatology & Skin Health Center — Birmingham
• Arkansas Research Trials — North Little Rock
• Investigational Drug Service - Rady Childrens Hospital-San Diego — San Diego
• University of California, San Diego/ Rady Children's Hospital - San Diego — San Diego
• Solutions Through Advanced Research — Jacksonville
• Dawes Fretzin Clinical Research Group, LLC — Indianapolis
• Medical University of South Carolina — Charleston
• Tribe Clinical Research, LLC — Greenville
• … и ещё 1 центр

Китай · 7 центров

• Beijing Children's hospital, Capital Medical University — Пекин
• Shenzhen Children's Hospital — Шэньчжэнь
• Hunan Children's Hospital — Чанша
• Dermatology Hospital of Jiangxi Province — Nanchang
• Hangzhou Third People's Hospital — Ханчжоу
• Shanghai Children's Hospital — Шанхай
• Xinhua Hospital Affiliated to Shanghai JiaoTong University School of Medicine — Шанхай

Польша · 6 центров

• LUXDERM Specjalistyczny Gabinet Dermatologiczny prof. dr hab. n. med. Dorota Krasowska — Lublin
• Centrum Medyczne Evimed — Warsaw
• DERMAPOLIS Medical Dermatology Center dr n. med. Edyta Gebska — Chorzów
• Centrum Medyczne Angelius Provita — Katowice
• Dermoklinika - Centrum Medyczne spółka cywilna M. Kierstan, J. Narbutt, A. Lesiak — Lodz
• Dermedic Jacek Zdybski — Ostrowiec Świętokrzyski

Япония · 5 центров

• Queen's square Medical Facilities Queen's square Dermatology and Allergology — Yokohama
• Dermatology and Ophthalmology Kume Clinic — Sakai
• Sasamoto Children's Clinic — Setagaya-ku
• Fukuoka National Hospital — Fukuoka
• Saruta Dermatology Clinic — Fukuoka

Мексика · 3 центра

• Eukarya Pharmasite S.C. — Monterrey
• Arké SMO S.A de C.V — Veracruz
• Servicios Hospitalarios de Mexico S.A. DE C.V. — Chihuahua City

Испания · 3 центра

• CHUS - Hospital Clinico Universitario — Santiago de Compostela
• Hospital General de Granollers — Granollers
• Hospital Universitario Miguel Servet — Zaragoza

Германия · 2 центра

• Universitätsklinikum Münster — Münster
• Universitaetsklinikum Carl Gustav Carus, Technischen Universitaet Dresden — Dresden

Венгрия · 2 центра

• Pécsi Tudományegyetem Klinikai Központ — Pécs
• Clinexpert Kft. — Budapest

Идентификаторы

NCT: NCT06807281 · B7451031 · 2023-509124-18-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗