Lebrikizumab in Moderate-to-severe Atopic Dermatitis

Официальное название

A Phase IV, Non-randomized, Open-label Multinational Trial to Assess the Mechanism of Action for Lebrikizumab in Moderate-to-severe Atopic Dermatitis

Обзор

This research is studying a drug already approved for the treatment of atopic dermatitis (AD). This research collects health-related information and blood and skin samples to understand if the study drug, lebrikizumab, leads to long-term improvement in AD skin.

Подробное описание

Lebrikizumab, the drug used in the study, has been deemed IND exempt by the FDA.

Вмешательства

• Препарат lebrikizumab
  Patients will receive lebrikizumab with a 500 mg loading dose administered subcutaneously at baseline and Week 2 followed by 250 mg every 2 weeks until Week 24. At week 24, patients with ≥ Eczema Area and Severity Index (EASI) 50 will continue in the study and begin receiving lebrikizumab 250mg every 4 weeks (Q4W), while patients with \<EASI 50 will be discontinued from the study. At week 36, patients with EASI ≥50 to \<90 will remain on Q4W through W60 (do not enter withdrawal arm), while pat

Первичные конечные точки

• Degree of normalization of transcriptomic/epigenetic profile [Срок оценки: Up to week 60]

Вторичные конечные точки (5)

• Molecular response to Lebrikizumab [Срок оценки: weeks 36 to 60]
• Skin barrier function [Срок оценки: Up to week 60]
• Clinical response as assessed be the Eczema Area and Severity Index (EASI) [Срок оценки: Up to week 60]
• Clinical response as assessed using the investigator global assessment (IGA) [Срок оценки: Up to week 60]
• Clinical response as assessed using the Peak Pruritus Numerical Rating Scale (NRS) (Pruitis NRS) [Срок оценки: Up to week 60]

Критерии участия

Критерии включения

• Established diagnosis of AD for at least 1 year before the screening visit and topical treatment was inadequate or inadvisable.
• Moderate-to-severe AD with involvement > 10% of body-surface-area (BSA) and investigator global assessment (IGA) score =3 (based on the IGA scale ranging from 0 to 4, in which 3 is moderate and 4 is severe) at both the screening and baseline visits.
• Subject has an Eczema Area and Severity Index (EASI) score =16 at screening and baseline.
• Subject has a pruritus NRS =4.
• Subject is biologic naïve.
• Female subjects of childbearing potential (i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile) must agree either to commit to true abstinence throughout the study and for at least 17 weeks after the last study drug (SD) injection, when this is in line with the preferred and usual lifestyle of the subject, or to use a highly-effective and approved method of contraception throughout the study and for at least 17 weeks after the last study drug injection.
• Subject willing and able to comply with all of the clinical study protocol's time commitments and procedural requirements.
• Understand and sign an informed consent form (ICF) (and assent form, when applicable) before any investigational procedure(s) are performed.

Критерии исключения

• Previous treatment with lebrikizumab or participation in a lebrikizumab study.
• History of anaphylaxis as defined by the Sampson criteria.
• Treatment with topical corticosteroids, calcineurin inhibitors, Jak inhibitors, or crisaborole within 1 week prior to the baseline visit.
• Prior treatment with dupilumab or tralokinumab.
• Treatment with any of the following agents within 4 weeks prior to the baseline visit:

• Immunosuppressive/immunomodulating drugs (e.g., systemic corticosteroids, cyclosporine, mycophenolate-mofetil, IFN-., Janus kinase inhibitors (JAKi), azathioprine, methotrexate).
• Phototherapy and photochemotherapy (PUVA) for AD.
• Treatment with the following prior to the baseline visit:

• An investigational drug within 8 weeks or 5 half-lives (if known), whichever is longer.
• Cell-depleting biologics, including to rituximab, within 6 months.
• Other biologics within 5 half-lives (if known) or 16 weeks, whichever is longer.
• Use of prescription moisturizers within 7 days of the baseline visit.
• Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks of the screening visit.
• Treatment with a live (attenuated) vaccine within 12 weeks of the baseline visit or planned during the study.
• Uncontrolled chronic disease that might require bursts of oral corticosteroids, e.g., co-morbid severe uncontrolled asthma requiring systemic \[oral and/or parenteral\] corticosteroid treatment or hospitalization for > 24 hours).
• Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, anti-parasitics, antiprotozoals, or antifungals within 2 weeks before the baseline visit, or superficial skin infections within 1 week before the baseline visit. NOTE: patients may be rescreened after infection resolves.
• Evidence of active acute or chronic hepatitis (as defined by the Department of Health \& Human Services Centers for Disease Control and Prevention) or known liver cirrhosis.
• Diagnosed active endoparasitic infections or at high risk of these infections.
• Known or suspected history of immunosuppression, including history of invasive opportunistic infections (e.g., tuberculosis \[TB\], histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, and aspergillosis) despite infection resolution: or unusually frequent, recurrent, or prolonged infections, per the Investigator's judgment.
• History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening.
• In the Investigator's opinion, any clinically significant laboratory results from the chemistry, hematology or urinalysis tests available in the medical history.
• Presence of skin comorbidities that may interfere with study assessments.
• History of malignancy, including mycosis fungoides, within 5 years before the screening visit, except completely treated in situ carcinoma of the cervix, completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin.
• Severe concomitant illness(es) that in the Investigator's judgment would adversely affect the patient's participation in the study. Any other medical or psychological condition that in the opinion of the Investigator may suggest a new and/or insufficiently understood disease, may present an unreasonable risk to the study patient because of his/her participation in this clinical trial, may make patient's participation unreliable, or may interfere with study assessments.

20\. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

США · 2 центра

• Physioseq USA - CA — Folsom
• University of Michigan — Ann Arbor

Германия · 1 центр

• University of Freiburg — Freiburg im Breisgau

Швейцария · 1 центр

• Lausanne University Hospital — Lausanne

Идентификаторы

NCT: NCT06906497 · HUM00261982

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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