Study To Evaluate Pf-04965842 In Subjects With Moderate To Severe Atopic Dermatitis

Study Overview
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Brief Summary
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Study B7451006 is a Phase 2b POC study which is planned to assess four PF 04965842 once daily (QD) doses (10, 30, 100, 200 mg) relative to placebo over 12 weeks to characterize the efficacy and safety of PF 04965842 in subjects with moderate to severe AD. The objectives of the study are to demonstrate the efficacy of PF 04965842 by showing improvement in disease severity in patients with moderate to severe AD as measured by the Investigator's Global Assessment (IGA) and Eczema Area and Severity Index (EASI) scores, and safety to support further clinical development of PF 04965842.

Official Title
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A PHASE 2B RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL, MULTICENTER, DOSE-RANGING, STUDY TO EVALUATE THE EFFICACY AND SAFETY PROFILE OF PF-04965842 IN SUBJECTS WITH MODERATE TO SEVERE ATOPIC DERMATITIS

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: PF-04965842
* Drug: PF-04965842
* Drug: PF-04965842
* Drug: PF-04965842
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects between 18 75 years of age, inclusive, at time of informed consent. Must have the following atopic dermatitis criteria: Have a clinical diagnosis of chronic atopic dermatitis (also known as atopic eczema) for at least 1 year prior to Day 1 and has confirmed atopic dermatitis (Hanifin and Rajka criteria of AD refer to Appendix 2) at the Screening visit. Have inadequate response to treatment with topical medications given for at least 4 weeks, or for whom topical treatments are otherwise medically inadvisable (eg, because of important side effects or safety risks) within 12 months of the first dose of study drug. Moderate to severe AD (affected BSA >=10 %, IGA >=3, and EASI >=12 at the screening and baseline visits). Exclusion Criteria: History of human immunodeficiency virus (HIV) or positive HIV serology at screening, Infected with hepatitis B or hepatitis C viruses. Have evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB) Have received any of the following treatment regiments specified in the timeframes outlined below: Within 6 months of first dose of study drug: Any cell depleting agents Within 12 weeks of first dose of study drug: Any studies with JAK inhibitors; Other biologics Within 8 weeks of first dose of study drug: Participation in other studies involving investigational drug(s) Within 6 weeks of first dose of study drug: Have been vaccinated with live or attenuated live vaccine. Within 4 weeks of first dose of study drug: Use of oral immune suppressants; Phototherapy (NB UVB) or broad band phototherapy; Regular use (more than 2 visits per week) of a tanning booth/parlor. Within 1 week of first dose of study drug: Topical treatments that could affect atopic dermatitis; Herbal medications with unknown properties or known beneficial effects for AD.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>10 mg of PF-04965842 QD | Drug: PF-04965842<br>* 10 mg of PF-04965842 QD for 12 weeks<br>|
| Experimental: Cohort 2<br>30 mg of PF-04965842 QD | Drug: PF-04965842<br>* 30 mg of PF-04965842 QD for 12 weeks<br>|
| Experimental: Cohort 3<br>100 mg of PF-04965842 QD | Drug: PF-04965842<br>* 100 mg of PF-04965842 QD for 12 weeks<br>|
| Experimental: Cohort 4<br>200 mg of PF-04965842 QD | Drug: PF-04965842<br>* 200 mg of PF-04965842 QD for 12 weeks<br>|
| Placebo Comparator: Cohort 5<br>placebo QD | Drug: Placebo<br>* Placebo QD for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving the Investigator's Global Assessment (IGA) for Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Week 12 | The IGA score quantifies the severity of participants' atopic dermatitis (AD). Scores range from 0 to 4 and correspond to a category (clear, almost clear, mild, moderate and severe, respectively). | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in the Eczema Area and Severity Index (EASI) at Week 12 | The EASI quantifies the severity of participants' AD based on both severity of lesion clinical signs and the percent of body surface area (BSA) affected. EASI is a composite scoring by the AD clinical evaluator of the degree of erythema, induration/population, excoriation, and lichenification (each scored separately) for each of 4 regions, with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of AD. | Baseline and Week 12 | 
| Percentage of Participants Achieving the IGA for Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at All Scheduled Time Points Except Week 12 | The IGA score quantifies the severity of participants' AD. Scores range from 0 to 4 and correspond to a category (clear, almost clear, mild, moderate and severe, respectively). | Baseline and all scheduled time points except Week 12, including Weeks 1, 2, 4, 6, 8, 13, 14, 16. | 
| Percentage of Participants Achieving >=2 Points Improvement in the IGA From Baseline at All Scheduled Time Points | The IGA score quantifies the severity of participants' AD. Scores range from 0 to 4 and correspond to a category (clear, almost clear, mild, moderate and severe, respectively). | Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16 | 
| Percent Change From Baseline in the EASI Total Score at All Scheduled Time Points Except Week 12. | The EASI quantifies the severity of participants' AD based on both severity of lesion clinical signs and the percent of BSA affected. EASI is a composite scoring by the AD clinical evaluator of the degree of erythema, induration/population, excoriation, and lichenification (each scored separately) for each of 4 regions, with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of AD. | Baseline and all scheduled time points except Week 12, including Weeks 1, 2, 4, 6, 8, 13, 14, 16 | 
| Percentage of Participants Achieving >=3 Points Improvement in the Pruritus Numerical Rating Scale (NRS) From Baseline at All Scheduled Time Points | The severity of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants were asked to assess their worst itching due to AD over the past 24 hours on a NRS anchored by the terms no itching (0) and worst possible itching (10). The frequency of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants were asked to assess their frequency of itching due to AD over the past 24 hours on a NRS anchored by the terms never/no itching (0) and always/constant itching (10). | Baseline and all scheduled time points, including Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 29, 43, 57, 85, 99, 113 | 
| Percentage of Participants Achieving >=4 Points Improvement in the Pruritus NRS From Baseline at All Scheduled Time Points | The severity of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants were asked to assess their worst itching due to AD over the past 24 hours on a NRS anchored by the terms no itching (0) and worst possible itching (10). The frequency of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants were asked to assess their frequency of itching due to AD over the past 24 hours on a NRS anchored by the terms never/no itching (0) and always/constant itching (10). | Baseline and all scheduled time points, including Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 29, 43, 57, 85, 99, 113 | 
| Time to Achieving >=3 Points Improvement in NRS | The severity of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants were asked to assess their worst itching due to AD over the past 24 hours on a NRS anchored by the terms no itching (0) and worst possible itching (10). The frequency of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants were asked to assess their frequency of itching due to AD over the past 24 hours on a NRS anchored by the terms never/no itching (0) and always/constant itching (10). | Baseline till Week 16 | 
| Time to Achieving >=4 Points Improvement in NRS | The severity of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants were asked to assess their worst itching due to AD over the past 24 hours on a NRS anchored by the terms no itching (0) and worst possible itching (10). The frequency of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants were asked to assess their frequency of itching due to AD over the past 24 hours on a NRS anchored by the terms never/no itching (0) and always/constant itching (10). | Baseline till Week 16 | 
| Percent Change From Baseline in the Pruritus NRS From Baseline at All Scheduled Time Points | The severity of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants were asked to assess their worst itching due to AD over the past 24 hours on a NRS anchored by the terms no itching (0) and worst possible itching (10). The frequency of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants were asked to assess their frequency of itching due to AD over the past 24 hours on a NRS anchored by the terms never/no itching (0) and always/constant itching (10). | Baseline and all scheduled time points, including Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 29, 43, 57, 85, 99, 113 | 
| Change From Baseline in Pruritus NRS Score at All Scheduled Time Points | The severity of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants were asked to assess their worst itching due to AD over the past 24 hours on a NRS anchored by the terms no itching (0) and worst possible itching (10). The frequency of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants were asked to assess their frequency of itching due to AD over the past 24 hours on a NRS anchored by the terms never/no itching (0) and always/constant itching (10). | Baseline and all scheduled time points, including Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 29, 43, 57, 85, 99, 113 | 
| Percentage of Participants Achieving a >=50% Improvement in the EASI Total Score (EASI50) at All Scheduled Time Points | The EASI quantifies the severity of participants' AD based on both severity of lesion clinical signs and the percent of BSA affected. EASI is a composite scoring by the AD clinical evaluator of the degree of erythema, induration/population, excoriation, and lichenification (each scored separately) for each of 4 regions, with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of AD. | All scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16 | 
| Percentage of Participants Achieving a >=75% Improvement in the EASI Total Score (EASI75) at All Scheduled Time Points | The EASI quantifies the severity of participants' AD based on both severity of lesion clinical signs and the percent of BSA affected. EASI is a composite scoring by the AD clinical evaluator of the degree of erythema, induration/population, excoriation, and lichenification (each scored separately) for each of 4 regions, with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of AD. | All scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16 | 
| Percentage of Participants Achieving a >=90% Improvement in the EASI Total Score (EASI90) at All Scheduled Time Points | The EASI quantifies the severity of participants' AD based on both severity of lesion clinical signs and the percent of BSA affected. EASI is a composite scoring by the AD clinical evaluator of the degree of erythema, induration/population, excoriation, and lichenification (each scored separately) for each of 4 regions, with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of AD. | All scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16 | 
| Change From Baseline in Affected BSA at All Scheduled Time Points | BSA Efficacy is derived from the sum of the BSA in handprints across 4 body regions assessed as part of the EASI assessment. Handprint refers to that of each individual participant for their own measurement. The BSA Efficacy ranges from 0 to 100%, with higher values representing greater severity of AD. Since the scalp, palms, and soles are excluded from the BSA (Efficacy) assessment, the maximum possible value is less than 100%. | Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16 | 
| Change From Baseline in Scoring Atopic Dermatitis (SCORAD) at All Scheduled Time Points | SCORAD is a validated scoring index for AD, which combines extent (0-100), severity (0-18), and subjective symptoms (0-20) based on pruritus and sleep loss, each scored (0-10). Extent, denoted as A, is measured by BSA affected by AD as a percentage of the whole BSA. The score for each body region is added up to determine A (maximum of 100%). Severity, denoted as B, consists of the severity of several signs. Each is assessed as none(0), mild(1), moderate(2) or severe(3). The severity scores are added together to give B (maximum of 18). Subjective symptoms, denoted as C, are each scored by the subject or caregiver using a numeric rating scale (NRS) where 0 is no itch (or no sleeplessness) and 10 is the worst imaginable itch (or sleeplessness). These scores are added to give 'C' (maximum of 20). The SCORAD for an individual is calculated by the formula: A/5 + 7B/2 + C (can range from 0 to 103). Higher values of SCORAD represent worse outcome. | Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16 | 
| Percent Change From Baseline in SCORAD at All Scheduled Time Points | SCORAD is a validated scoring index for AD, which combines extent (0-100), severity (0-18), and subjective symptoms (0-20) based on pruritus and sleep loss, each scored (0-10). Extent, denoted as A, is measured by BSA affected by AD as a percentage of the whole BSA. The score for each body region is added up to determine A (maximum of 100%). Severity, denoted as B, consists of the severity of several signs. Each is assessed as none(0), mild(1), moderate(2) or severe(3). The severity scores are added together to give B (maximum of 18). Subjective symptoms, denoted as C, are each scored by the subject or caregiver using a numeric rating scale (NRS) where 0 is no itch (or no sleeplessness) and 10 is the worst imaginable itch (or sleeplessness). These scores are added to give 'C' (maximum of 20). The SCORAD for an individual is calculated by the formula: A/5 + 7B/2 + C (can range from 0 to 103). Higher values of SCORAD represent worse outcome. | Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16 | 
| Percentage of Participants Achieving a >=50% Improvement in SCORAD (SCORAD50) From Baseline at All Scheduled Time Points | SCORAD is a validated scoring index for AD, which combines extent (0-100), severity (0-18), and subjective symptoms (0-20) based on pruritus and sleep loss, each scored (0-10). Extent, denoted as A, is measured by BSA affected by AD as a percentage of the whole BSA. The score for each body region is added up to determine A (maximum of 100%). Severity, denoted as B, consists of the severity of several signs. Each is assessed as none(0), mild(1), moderate(2) or severe(3). The severity scores are added together to give B (maximum of 18). Subjective symptoms, denoted as C, are each scored by the subject or caregiver using a numeric rating scale (NRS) where 0 is no itch (or no sleeplessness) and 10 is the worst imaginable itch (or sleeplessness). These scores are added to give 'C' (maximum of 20). The SCORAD for an individual is calculated by the formula: A/5 + 7B/2 + C (can range from 0 to 103). Higher values of SCORAD represent worse outcome. | Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16 | 
| Percentage of Participants Achieving a >=75% Improvement in SCORAD (SCORAD75) From Baseline at All Scheduled Time Points | SCORAD is a validated scoring index for AD, which combines extent (0-100), severity (0-18), and subjective symptoms (0-20) based on pruritus and sleep loss, each scored (0-10). Extent, denoted as A, is measured by BSA affected by AD as a percentage of the whole BSA. The score for each body region is added up to determine A (maximum of 100%). Severity, denoted as B, consists of the severity of several signs. Each is assessed as none(0), mild(1), moderate(2) or severe(3). The severity scores are added together to give B (maximum of 18). Subjective symptoms, denoted as C, are each scored by the subject or caregiver using a numeric rating scale (NRS) where 0 is no itch (or no sleeplessness) and 10 is the worst imaginable itch (or sleeplessness). These scores are added to give 'C' (maximum of 20). The SCORAD for an individual is calculated by the formula: A/5 + 7B/2 + C (can range from 0 to 103). Higher values of SCORAD represent worse outcome. | Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16 | 
| Number of Participants With Treatment-emergent Adverse Events (AEs) | An AE was any untoward medical occurrence in a subject administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. Treatment-emergent AEs were events that occurred between the first dose of study drug and the subject's last visit (Week 16) that were absent before treatment or that worsened relative to pretreatment state. | Baseline till Week 16 | 
| Number of Participants With Specific Clinical Laboratory Abnormalities (Anemia, Neutropenia, Thrombocytopenia, Lymphopenia, Lipid Profile, Liver Function Tests (LFTs) |  | Baseline up to Week 16 | 
| Percentage of Participants With Patient Global Assessment (PtGA) of AD of Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at All Scheduled Time Points | The PtGA asked the participant to evaluate the overall cutaneous disease at that point in time on a single-item, 5-point scale. The same category labels used in the Physician's Global Assessment was used for the PtGA, ie, severe (4), moderate (3), mild (2),almost clear (1), and clear (0). The PtGA was completed as per schedule of activities. | Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 14, 16 | 
| Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at All Scheduled Time Points | The DLQI is a general dermatology questionnaire that consists of 10 items that assess participant health-related quality of life (daily activities, personal relationships, symptoms and feelings, leisure, work and school, and treatment). It has been extensively used in clinical trials for AD. The DLQI is a psychometrically valid and reliable instrument that has been translated into several languages, and the DLQI total scores have been shown to be responsive to change. The minimally important difference for the DLQI has been estimated as a 2-5 point change from baseline. Each item is scored as very much (3), a lot (2), a little (1) and not at all (0). The score can range from 0 to 30. The higher values represent the worse dermatology life quality. | Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 14, 16 | 
| Change From Baseline in Patient Oriented Eczema Measure (POEM) at All Scheduled Time Points | The POEM is a 7-item patient reported outcome (PRO) measure used to assess the impact of AD 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. The higher values represent more severe AD. | Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 14, 16 | 
| Change From Baseline in the Hospital and Anxiety Depression Scale (HADS) at All Scheduled Time Points | The HADS is a 14-item PRO measure used to detect states of anxiety and depression over the past week. The HADS was completed as per schedule of activities. Seven of the items relate to anxiety and seven relate to depression. Each item is scored from 0 to 3 which means a person can score between 0 to 21 for either anxiety or depression. Higher values represent worse outcome. | Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 14, 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 2, randomized, double-blind, placebo, atopic dermatitis, safety, efficacy, JAK, janus kinase, moderate, severe