A RANDOMIZED, OPEN-LABEL, PARALLEL-GROUP STUDY TO EVALUATE THE SAFETY AND EFFICACY OF ABROCITINIB 100 MG AND 200 MG TABLETS IN PARTICIPANTS AGED 12 YEARS AND OLDER WITH MODERATE TO SEVERE ATOPIC DERMATITIS IN INDIA
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 189
- 试验地点
- 15
- 主要终点
- Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs): Main Study
研究概览
简要总结
The purpose of this clinical trial is to learn about the safety and how well the study medicine (called Abrocitinib) works for the potential treatment of moderate to severe Atopic Dermatitis (AD) in India. AD, also known as atopic eczema, is a chronic, relapsing skin condition characterized by dry, itchy skin lesions which can affect any part of the body. Adult peoples who participate in this study will take either 100 mg or 200 mg of abrocitinib tablets by mouth for a duration of 12 weeks and adolescents will take for duration of 52 weeks. Knee Magnetic Resonance Imagine (MRI) will be done on adolescent peoples to determine bone safety findings. We will examine the experiences of people receiving the study medicines. This will help us determine if the study medicines are safe and how well they work.
详细描述
Abrocitinib is an oral, once daily Janus kinase 1 (JAK1) selective inhibitor for the treatment of moderate to severe Atopic Dermatitis (AD). Selective inhibition of JAK1 with abrocitinib modulates signaling by Interleukin-4 (IL-4), Interleukin (IL-13), and other cytokines [eg, IL-31, IL-22, and thymic stromal lymphopoietin (TSLP)] involved in the pathogenesis of Atopic Dermatitis and pruritus.
This is a randomized, open label, parallel group study to assess the safety and efficacy of orally administered tablets of abrocitinib in participants aged 12 years and older with moderate to severe AD in India. There is a planned treatment duration of 12 weeks, with 4 weeks of off-treatment safety follow up thereafter.
This study protocol also includes a sub-study evaluating whether abrocitinib has any potential effects on adolescent bone with regard to abnormal bone findings in knee magnetic resonance imaging (MRI). Adolescent participants (12 to <18 years of age) will continue to receive study intervention until 1 year after randomization into the main study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •This study is seeking participants who:
- •Must be of 12 years of age or older, at the time of informed consent.
- •Meet all the following Atopic Dermatitis (AD) criteria:
- •Clinical diagnosis of chronic AD (also known as atopic eczema) for at least 1 year prior to Day 1 and has confirmed AD (Hanifin and Rajka criteria of AD10).
- •Moderate to severe AD (affected body surface area (BSA) ≥10%, Investigator's Global Assessment (IGA) ≥3, Eczema Area and Severity Index (EASI) ≥16, and Peak Pruritus Numerical Rating Scale (PP-NRS) ≥4 at the baseline visit);
- •Documented recent history (within 6 months before the screening visit) of inadequate response to treatment with topical medications for at least 4 weeks, or for whom topical treatments are otherwise medically inadvisable (eg, because of important side effects or safety risks), or who have required systemic therapies for control of their disease.
- •Negative pregnancy test for females of childbearing potential at Screening. Female participants of childbearing potential must agree to use a highly effective method of contraception for the duration of the active treatment period and for at least 28 days after the last dose of study intervention.
- •Body weight ≥25 kg at Baseline
- •Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the Informed Consent Document (ICD) and in this protocol. Evidence of a personally signed and dated ICD indicating that the participant (or a legally acceptable representative, parent(s)/legal guardian) has been informed of all pertinent aspects of the study. For minors under the age of legal consent in India, assent of the participating child needs to be documented for the age range 12 to 18 years in addition to the parental informed consent.
排除标准
- •This study does not include participants who:
- •Currently have active forms of other inflammatory skin diseases or have evidence of skin conditions (eg, psoriasis, seborrheic dermatitis, lupus).
- •A current or past medical history of conditions associated with thrombocytopenia, coagulopathy or platelet dysfunction or QT interval abnormalities.
- •Have increased risk of developing venous thromboembolism, eg, deep vein thrombosis or pulmonary embolism:
- •Have a history of any lymphoproliferative disorder such as Epstein Barr virus (EBV) related lymphoproliferative disorder, history of lymphoma, leukemia, or signs or symptoms suggestive of current lymphatic or lymphoid disease.
- •Past history or active infection with Mycobacterium tuberculosis (TB), disseminated herpes zoster or disseminated herpes simplex, human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C.
- •Have any malignancies or have a history of malignancies with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin, or cervical carcinoma in situ.
- •Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgement, make the participant inappropriate for the study. Any psychiatric condition including recent or active suicidal ideation or behavior that met any of the following criteria when screened for during the main study:
- •Suicidal ideation associated with actual intent and a method or plan in the past year: "Yes" answers on items 4 or 5 of the Columbia suicide severity rating scale (C-SSRS);
- •Previous history of suicidal behaviors in the past 5 years: "Yes" answer (for events that occurred in the past 5 years) to any of the suicidal behavior items of the C-SSRS;
- •Any lifetime history of serious or recurrent suicidal behavior;
- •The presence of any current major psychiatric disorder that is not explicitly permitted in the inclusion/exclusion criteria;
- •In the opinion of the investigator or Pfizer (or designee) exclusion is required.
- •Prior treatment with systemic janus kinase (JAK) inhibitors.
- •Participants who are vaccinated with live attenuated vaccine within the 6 weeks prior to the first dose of abrocitinib or who are expected to be vaccinated with these vaccines during treatment or during the 6 weeks following discontinuation of abrocitinib.
- •Have received any of the following treatment regimens specified in the timeframes outlined below:
- •Within 1 year of first dose of study intervention:
- •Prior treatment with non B cell-specific lymphocyte depleting agents/therapies (eg, alkylating agents [eg, cyclophosphamide or chlorambucil], total lymphoid irradiation, etc.). Participants who have received rituximab or other selective B lymphocyte depleting agents (including experimental agents) are eligible if they have not received such therapy for at least 1 year prior to study baseline and have normal cluster of differentiation (CD) 19/20+ counts by fluorescence activated cell sorting (FACS) analysis.
- •Within 12 weeks of first dose of study intervention:
- •Biologic drugs that have immunomodulatory properties or could be used to treat AD: within 12 weeks of first dose of investigational product or 5 half-lives (if known), whichever is longer.
- •Other biologics without immunomodulatory properties (eg, insulin) are permissible at the judgement of the Investigator.
- •Within 4 weeks of first dose of study intervention:
- •Use of oral immunosuppressive drugs (eg, Cyclosporine A (CsA), azathioprine, methotrexate, systemic corticosteroids, mycophenolate mofetil, Interferon gamma) within 4 weeks of first dose of study intervention or within 5 half-lives (if known), whichever is longer.
- •NOTE: Systemic corticosteroids must be discontinued before Study Day 1, but a specific timeframe for discontinuation prior to first dose of abrocitinib is not required.
- •NOTE: Corticosteroid inhalers and intranasal sprays are permissible. NOTE: Ophthalmic corticosteroids are permissible.
- •Within 1 week of first dose of study intervention:
- •Anti-platelet drugs. Note: low dose acetyl salicylic acid (<100 mg once daily [QD]) is permitted, for the purpose of cardiovascular prophylaxis, at the discretion of the investigator.
- •Require treatment with prohibited concomitant medication(s) or have received a prohibited concomitant medication.
- •Participation in other studies involving investigational drug(s) or vaccine within 8 weeks or within 5 half-lives (if known) whichever is longer, prior to study entry and/or during study participation.
- •Any of the following abnormalities in clinical laboratory tests at Screening:
- •Absolute neutrophil count of <1.0 × 109/L (<1000/mm3);
- •Platelet count of <150 × 109/L (<150,000/mm3);
- •Absolute lymphocyte count of <0.50 × 109/L (<500/mm3);
- •Estimated Creatinine Clearance <60 mL/min using the Cockcroft Gault method;
- •Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) values >2 times the Upper Limit of Normal (ULN);
- •Total Bilirubin (TBili) ≥1.5 times the ULN.
- •Pregnant or breastfeeding women, or women of childbearing potential who are unwilling to use highly effective contraception consistently and correctly for the entire duration of the study and for at least 28 days after the last dose of study intervention.
- •Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
研究组 & 干预措施
Abrocitinib 100 mg
Participants will receive abrocitinib 100 mg by mouth (QD).
干预措施: Abrocitinib 100 mg (Drug)
Abrocitinib 200 mg
Participants will receive abrocitinib 200 mg QD.
干预措施: Abrocitinib 200 mg (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs): Main Study
时间窗: From Day 1 of dosing up to 4 weeks post last dose (maximum up to Week 16)
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic or other situations where medical or scientific judgement should be exercised by investigator. AEs included SAEs and all non-SAEs.
次要结局
- Percentage of Participants Who Achieved Investigator's Global Assessment (IGA) Score of Clear (0) or Almost Clear (1) and >= 2 Points Improvement From Baseline at Week 12: Main Study(Baseline (prior to dosing on Day 1), Week 12)
- Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response >= 75% Improvement From Baseline at Week 12: Main Study(Baseline (prior to dosing on Day 1), Week 12)
- Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >= 75% Improvement From Baseline at Week 12: Main Study(Baseline (prior to dosing on Day 1), Week 12)
- Change From Baseline in Patient-Oriented Eczema Measure (POEM) Score at Weeks 2, 4, 8 and 12: Main Study(Baseline (prior to dosing on Day 1), Weeks 2, 4, 8 and 12)
- Change From Baseline in Atopic Dermatitis Control Tool (ADCT) Score at Weeks 2, 4, 8 and 12: Main Study(Baseline (prior to dosing on Day 1), Weeks 2, 4, 8 and 12)
- Percentage of Participants With Bone Safety Findings in Knee Magnetic Resonance Imaging (MRI) at 1 Year After Randomization: Substudy(Up to 1 year from randomization on Day 1 of main study)