A Study to Learn About Abrocitinib Tablets in People With Atopic Dermatitis in India

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Abrocitinib 100 mg
* Drug: Abrocitinib 200 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 12 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abrocitinib 100 mg<br>Participants will receive abrocitinib 100 mg by mouth (QD). | Drug: Abrocitinib 100 mg<br>* Orally administered, abrocitinib 100 mg tablets QD<br>|
| Experimental: Abrocitinib 200 mg<br>Participants will receive abrocitinib 200 mg QD. | Drug: Abrocitinib 200 mg<br>* Orally administered, abrocitinib 200 mg tablets QD.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (AEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. | From the time of first dose to Week 16 for main study. From the time of first dose to week 56 for sub-study. | 
| Number of Participants with Serious Adverse Events (SAEs) | SAE was defined as one of the following: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. | From the time of first dose to Week 16 for main study. From the time of first dose to week 56 for sub-study. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants receiving Investigator's Global Assessment (IGA) response of clear (0) or almost clear (1) and greater than or equal to 2 points improvement | IGA assesses severity of Atopic Dermatitis (AD) on a 5 point scale (0 to 4, higher scores indicate more severity). Scores: 0= clear, no inflammatory signs of AD; 1= almost clear, AD not fully cleared- light pink residual lesions (except post-inflammatory hyperpigmentation), just perceptible erythema, papulation/induration lichenification, excoriation, and no oozing/crusting; 2= mild AD with light red lesions, slight but definite erythema, papulation/induration, lichenification, excoriation and no oozing/crusting; 3= moderate AD with red lesions, moderate erythema, papulation/induration, lichenification, excoriation and slight oozing/crusting; 4= severe AD with deep dark red lesions, severe erythema, papulation/induration, lichenification, excoriation and moderate to severe oozing/crusting. | From baseline at Week 12. | 
| Percentage of participants achieving Eczema Area and Severity Index (EASI) of ≥75% improvement from baseline in the EASI total score (EASI-75) at Week 12. | EASI evaluates severity of participant's AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions(head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in each 4 body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD. | Baseline to week 12 | 
| Percentage of Participants With Scoring Atopic Dermatitis (SCORAD) Response of >=75% Improvement From Baseline at Week 12s | SCORAD evaluates extent (0-100), severity (0-18), and subjective symptoms (0-20) of AD based on pruritus and sleep loss, each scored using a visual analog scale (0-10). | Baseline to Week 12 | 
| Number of participants with change from baseline in Patient-Oriented Eczema Measure (POEM) at Week 12 and at all scheduled time points. | POEM is a 7-item participant reported outcome (PRO) measure used to assess the impact of AD (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) over the past week. Each item is scored as no days (0), 1-2 days (1), 3-4 days (2), 5-6 days (3) and every day (4). The score ranges from 0 to 28, where higher score indicated greater severity. | Baseline to week 12 | 
| Number of participants with change from baseline in Atopic Dermatitis Control Tool (ADCT) at Week 12 and at all scheduled time points. | The Atopic Dermatitis Control Tool (ADCT) is a brief patient self-administered instrument designed and validated to assess patient-perceived AD control; AD symptoms and impacts are evaluated over the past week, including overall severity of symptoms, days with intense episodes of itching, intensity of bother, problem with sleep, impact on daily activities, and impact on mood or emotions | Baseline to week 12 | 
| The proportion of abnormal bone findings in knee MRI 1 year after randomization in adolescent participants. | Incidence of abnormal bone findings in knee MRI after 1 year of being exposed to abrocitinib in adolescent participants 12 to <18 years of age, regardless of dosing compliance or treatment discontinuation. | Baseline to 1 year after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AD, Atopic Eczema