A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTI-CENTER STUDY INVESTIGATING THE EFFICACY AND SAFETY OF PF-04965842 CO-ADMINISTERED WITH BACKGROUND MEDICATED TOPICAL THERAPY IN ADOLESCENT PARTICIPANTS 12 TO <18 YEARS OF AGE WITH MODERATE-TO-SEVERE ATOPIC DERMATITIS

Brief Summary

Detailed Description

This is a randomized, double blind, placebo controlled, parallel group, Phase 3 study to evaluate the efficacy and safety of PF 04965842 in adolescent participants 12 to \<18 years of age with moderate to severe AD. Participants will be screened within 28 days prior to the first dose of study intervention to confirm study eligibility. Subjects must have moderate-severe AD involving at least 10% Body Surface Area (BSA); an Investigator Global Assessment (IGA) score of at least 3; an Eczema Area Severity Index (EASI) of at least 16 and Peak Pruritus Numerical Rating Score (NRS) of at least 4 on baseline/Day 1. Eligible subjects will be randomized at the Baseline/Day 1 visit. Approximately 225 participants will be randomized in a 1:1:1 ratio to receive once daily PF 04965842 at 200 mg, 100 mg, or placebo for 12 weeks. Randomization will be stratified by baseline disease severity (moderate \[IGA = 3\] vs. severe \[IGA = 4\] AD). The investigational products will be administered QD for 12 weeks. Background therapy (medicated and non-medicated topical therapy) must be applied BID for the duration of the treatment period. The co-primary efficacy endpoints are an IGA score of clear (0) or almost clear (1) with a reduction from baseline of greater than 2 points at Week 12 AND an at least 75% improvement of the EASI score (EASI-75) at week 12. Safety and efficacy assessments will be conducted at the investigator site by a clinical assessor blinded to treatment assignment. Scheduled clinic or telephone study visits for all subjects will occur at Screening, Baseline/Day 1, Day 8 (by phone), Day 15, Day 29, Day 43 (by phone), Day 57, Day 85 (End of treatment/Early termination), Day 113 (End of Study). Participants discontinuing early from the study will undergo a 4 week follow up period. This study includes an immunogenicity sub study integrated into the last 4 weeks of the main study treatment period. At Week 8, up to approximately 90 participants (up to approximately 30 in each treatment arm) who have completed 8 weeks of treatment with study intervention will receive a tetanus, diphtheria and acellular pertussis combination vaccine (Tdap), and collection of blood samples for the evaluation of immunogenicity at Weeks 8 and 12. Participants of this sub study will complete all other protocol specified procedures in the main study. At the end of the 12 week study treatment, qualified participants completing the study will have the option to enter the long term extension (LTE) study B7451015.

Primary Outcomes

Secondary Outcomes

• Percentage of Participants Achieving EASI Response =100% Improvement From Baseline(Baseline, Weeks 2, 4, 8 and 12)
• Percentage of Participants Achieving ≥4 Points Improvement From Baseline in PP-NRS for Severity of Pruritus at All Scheduled Time Points Other Than Weeks 2, 4 and 12(Baseline, Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15)
• Change From Baseline in Dermatitis Family Impact (DFI) at Week 12(Baseline to Week 12)
• Change From Baseline in Patient Global Assessment (PtGA)(Baseline, Weeks 2, 4, 8 and 12)
• Percentage of Participants With ≥2 Points at Baseline and Achieving 'Clear' or 'Almost Clear' and ≥2 Points Improvement From Baseline in PtGA(Baseline, Weeks 2, 4, 8 and 12)
• Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) at Week 12(Baseline to Week 12)
• Percent Change From Baseline in SCORAD Subjective VAS of Sleep Loss(Baseline, Weeks 2, 4, 8 and 12)
• Percentage of Participants Achieving ≥4 Points Improvement From Baseline in Peak Pruritis Numeric Rating Scale (PP-NRS) for Severity of Pruritus at Weeks 2, 4 and 12(Baseline, Weeks 2, 4 and 12)
• Percentage of Participants Achieving IGA Response of 'Clear' or 'Almost Clear' and ≥2 Points Improvement From Baseline at All Scheduled Time Points Except Week 12(Baseline, Weeks 2, 4 and 8)
• Percentage of Participants Achieving EASI Response ≥ 75% Improvement From Baseline at All Scheduled Time Points Except Week 12(Baseline, Weeks 2, 4 and 8)
• Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response ≥ 50% Improvement From Baseline(Baseline, Weeks 2, 4, 8 and 12)
• Percentage of Participants Achieving SCORAD Response ≥ 75% Improvement From Baseline(Baseline, Weeks 2, 4, 8 and 12)
• Change From Baseline in SCORAD Total Score(Baseline, Weeks 2, 4, 8 and 12)
• Percent Change From Baseline in SCORAD Total Score(Baseline, Weeks 2, 4, 8 and 12)
• Change From Baseline in Children's Dermatology Life Quality Index (DLQI)(Baseline, Weeks 2, 4, 8 and 12)
• Percentage of Participants Achieving EASI Response ≥ 50% Improvement From Baseline(Baseline, Weeks 2, 4, 8 and 12)
• Percentage of Participants Achieving EASI Response ≥ 90% Improvement From Baseline(Baseline, Weeks 2, 4, 8 and 12)
• Percent Change From Baseline in EASI Score(Baseline, Weeks 2, 4, 8 and 12)
• Time to First Achieve ≥4 Points Improvement From Baseline in PP-NRS for Severity of Pruritus(Baseline to Week 16)
• Percent Change From Baseline in Percentage BSA(Baseline, Weeks 2, 4, 8 and 12)
• Percentage of Participants Achieving Percentage BSA < 5% at Week 12(Baseline to Week 12)
• Number of Days When a Corticosteroid Not Used up to Day 88(Baseline to Day 88)
• Percent Change From Baseline in PP-NRS for Severity of Pruritus(Baseline, Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15)
• Change From Baseline in Percentage Body Surface Area (BSA)(Baseline, Weeks 2, 4, 8 and 12)
• Change From Baseline in SCORAD Subjective Visual Analogue Scale (VAS) of Sleep Loss(Baseline, Weeks 2, 4, 8 and 12)
• Percentage of Participants With ≥2.5 Points at Baseline and Achieving ≥2.5 Points Improvement From Baseline in Children's DLQI(Baseline, Weeks 2, 4, 8 and 12)
• Change From Baseline in Anxiety of Hospital Anxiety and Depression Scale (HADS)(Baseline, Weeks 2, 4, 8 and 12)
• Change From Baseline in Depression of HADS(Baseline, Weeks 2, 4, 8 and 12)
• Change From Baseline in Patient-Oriented Eczema Measure (POEM)(Baseline, Weeks 2, 4, 8 and 12)
• Change From Baseline in EuroQol Quality of Life 5-Dimension Youth Scale (EQ-5D-Y) VAS Score(Baseline, Weeks 2, 4, 8 and 12)
• Change From Baseline in Pediatric Functional Assessment of Chronic Illness Therapy Fatigue Scale (Peds-FACIT-F) at Week 12(Baseline to Week 12)
• Number of Participants With Treatment Emergent Adverse Events (TEAEs)(16 weeks)
• Number of Participants With Serious Adverse Events (SAEs)(16 weeks)
• Number of Participants Who Discontinued From the Study Due to TEAEs(16 weeks)
• Number of Participants With Electrocardiogram (ECG) Data Meeting Prespecified Criteria(16 weeks)
• Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)(16 weeks)
• Categorization of Vital Signs Data Meeting Prespecified Criteria(16 weeks)
• Fold Increase of Immunoglobulin G (IgG) Concentrations Against Specific Vaccine Antigens at 4 Weeks Post-Vaccination(4 weeks post-vaccination with Tdap (Week 12))
• Plasma PF-04965842 Concentration at Week 8(2 hours pre-dose at Week 8)
• Plasma PF-04965842 Concentration at Week 12(2 hours post-dose at Week 12)