Study to Investigate Efficacy and Safety of PF-04965842 in Subjects Aged 12 Years and Over With Moderate to Severe Atopic Dermatitis With the Option of Rescue Treatment in Flaring Subjects

• ClinicalTrials.gov Identifier: NCT03627767
• Recruitment Status: Completed
• First Posted: August 13, 2018
• Last Update Posted: November 24, 2020
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: May 29, 2018
• First Posted Date: August 13, 2018
• Last Update Posted Date: November 24, 2020
• Actual Study Start Date: June 11, 2018
• Actual Primary Completion Date: September 2, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 8, 2018)

Loss of response [ Time Frame: Randomization (Week 12) to Week 52 ]

Loss of response requiring rescue treatment will be evaluated and compared among groups during the blinded treatment period. Loss of response is denoted as flare and is defined as a loss of at least 50% of the Eczema Area and Severity Index (EASI) response at Week 12 and an Investigator's Global Assessment (IGA) score of 2 or higher.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 8, 2018)

• Investigator's Global Assessment (IGA) [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 28, 40, 52 and Rescue Weeks 0, 2, 4, 8, 12, and follow up (defined as 4 weeks post last dose) ]
  Response based on the IGA at all scheduled time points.
• Eczema Area and Severity Index (EASI) [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 28, 40, 52 and Rescue Weeks 0, 2, 4, 8, 12, and follow up (defined as 4 weeks post last dose) ]
  Response based on EASI total score at all scheduled time points.
• Pruritus Numberical Rating Scale (NRS) [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 28, 40, 52 and Rescue Weeks 0, 2, 4, 8, 12, and follow up (defined as 4 weeks post last dose) ]
  Response based on at least 4 points improvement in the severity of pruritus NRS from relevant baseline at all scheduled time points. Severity is on a scale of 0 to 10, with 0 being "no itch" and 10 being "worst itch imaginable."
• Body Surface Area (BSA) [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 28, 40, 52 and Rescue Weeks 0, 2, 4, 8, 12, and follow up (defined as 4 weeks post last dose) ]
  Change from relevant baseline in percent BSA at all scheduled time points.
• SCORing Atopic Dermatitis (SCORAD) [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 28, 40, 52 and Rescue Weeks 0, 2, 4, 8, 12, and follow up (defined as 4 weeks post last dose) ]
  Change from relevant baseline in SCORAD subjective assessments of itch and sleep loss at all scheduled time points. Includes proportion of subjects achieving a >=50% and >=75% improvement in SCORAD (SCORAD-50, SCORAD-75) from relevant baseline at all scheduled time points.
• Patient Global Assessment (PtGA) [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 28, 40, 52 and Rescue Weeks 0, 2, 4, 8, 12, and follow up (defined as 4 weeks post last dose) ]
  Change from relevant baseline in PtGA at all scheduled time points.
• Dermatology Life Quality Index (DLQI) or Children's DLQI (CDLQI) [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 28, 40, 52 and Rescue Weeks 0, 2, 4, 8, 12, and follow up (defined as 4 weeks post last dose) ]
  Change from relevant baseline in DLQI or CDLQI at all scheduled time points.
• Hospital Anxiety Depression Scale (HADS) [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 28, 40, 52 and Rescue Weeks 0, 2, 4, 8, 12, and follow up (defined as 4 weeks post last dose) ]
  Change from relevant baseline in HADS at all scheduled time points. Each question has 0 to 3 scale with 0 being the best "not at all/hardly at all" and 3 being the worst "most of the time/nearly all of the time."
• Patient Oriented Eczema Measure (POEM) [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 28, 40, 52 and Rescue Weeks 0, 2, 4, 8, 12, and follow up (defined as 4 weeks post last dose) ]
  Change from relevant baseline in POEM at all scheduled time points.
• Pruritus and symptoms Assessment in Atopic Dermatitis (PSAAD) [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 28, 40, 52 and Rescue Weeks 0, 2, 4, 8, 12, and follow up (defined as 4 weeks post last dose) ]
  Change from relevant baseline in the PSAAD at all scheduled time points.
• EuroQol Quality of LIfe 5-Dimension 5-Level Scale (EQ-5D-5L) or Youth Scale (EQ-5D-Y) [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 28, 40, 52 and Rescue Weeks 0, 2, 4, 8, 12, and follow up (defined as 4 weeks post last dose) ]
  Change from relevant baseline in EQ-5D-5L or EQ-5D-Y at all scheduled time points.
• Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F) or Pediatric FACIT-F (Peds-FACIT-F) [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 28, 40, 52 and Rescue Weeks 0, 2, 4, 8, 12, and follow up (defined as 4 weeks post last dose) ]
  Change from relevant baseline in FACIT-F or Peds-FACIT-F at all scheduled time points.
• Short Form-36, acute (SF-36) [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 28, 40, 52 and Rescue Weeks 0, 2, 4, 8, 12, and follow up (defined as 4 weeks post last dose) ]
  Change from relevant baseline in SF-36, acute (adults only) at all scheduled time points.
• Investigator's Global Assessment (IGA) [ Time Frame: Randomization (Week 12) to Week 52 ]
  Key Secondary Endpoint: Loss of response based on an IGA score of 2 or higher.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Investigate Efficacy and Safety of PF-04965842 in Subjects Aged 12 Years and Over With Moderate to Severe Atopic Dermatitis With the Option of Rescue Treatment in Flaring Subjects
• Official Title: A PHASE 3 RANDOMIZED WITHDRAWAL, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTI-CENTER STUDY INVESTIGATING THE EFFICACY AND SAFETY OF PF-04965842 IN SUBJECTS AGED 12 YEARS AND OVER, WITH MODERATE TO SEVERE ATOPIC DERMATITIS WITH THE OPTION OF RESCUE TREATMENT IN FLARING SUBJECTS
• Brief Summary: B7451014 is a Phase 3 study to investigate PF-04965842 in patients aged 12 years and over with a minimum body weight of 40 kg who have moderate to severe atopic dermatitis. Subjects responding well to an initial open-label 12 week treatment of PF-04965842 (200 mg) taken orally once daily (QD) will be identified and randomized in a double-blind manner to receive 200 mg QD PF-04965842, 100 mg QD PF-04965842, or QD placebo. Efficacy and safety of 2 doses of PF-04965842 will be evaluated relative to placebo over 40 weeks. Subjects experiencing significant worsening of their symptoms, i.e., protocol-defined flare, enter 12 weeks rescue treatment and receive 200 mg PF-04965842 together with a marketed topical medicine. Eligible patients will have the option to enter a long-term extension study after completing the initial 12 week treatment, the 12 week rescue treatment, and the 40 week blinded treatment.
• Detailed Description: Responder criteria for randomization at week 12 are defined as a) achieving an IGA of clear (0) or almost clear (1) (on a 5 point scale), b) a reduction from IGA baseline of 2 or more points, and c) reaching an EASI-75 response compared to baseline. Flare requiring rescue treatment is defined as a loss of at least 50% of the EASI response at Week 12 and an IGA score of 2 or higher.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Dermatitis
• Dermatitis, Atopic
• Eczema
• Skin Diseases
• Skin Diseases, Genetic
• Genetic Diseases, Inborn
• Skin Diseases, Eczematous
• Hypersensitivity
• Hypersensitivity, Immediate
• Immune System Diseases

Intervention

• Drug: PF-04965842 100 mg
  PF-04965842 100 mg, administered as two tablets to be taken orally once daily for 40 weeks
  Other Name: Abrocitinib
• Drug: PF-04965842 200 mg
  PF-04965842 200 mg, administered as two tablets to be taken orally once daily for 40 weeks
  Other Name: Abrocitinib
• Drug: Placebo
  Placebo, administered as two tablets to be taken orally once daily for 40 weeks

Study Arms

• Experimental: PF-04965842 100 mg QD
  Double-blind randomized treatment following open label run-in period.
  Intervention: Drug: PF-04965842 100 mg
• Experimental: PF-04965842 200 mg QD
  Double-blind randomized treatment following open label run-in period.
  Intervention: Drug: PF-04965842 200 mg
• Placebo Comparator: Placebo QD
  Double-blind randomized treatment following open label run-in period.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 20, 2020): 1234
• Original Estimated Enrollment (submitted: August 8, 2018): 1370
• Actual Study Completion Date: October 7, 2020
• Actual Primary Completion Date: September 2, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 12 years of age or older with a minimum body weight of 40 kg
• Diagnosis of atopic dermatitis (AD) for at least 1 year and current status of moderate to severe disease (>= the following scores: BSA10%, IGA 3, EASI 16, Pruritus NRS 4)
• Recent history of inadequate response or inability to tolerate topical AD treatments or require systemic treatments for AD control

Exclusion Criteria:

• Unwilling to discontinue current AD medications prior to the study or require treatment with prohibited medications during the study
• Prior treatment with JAK inhibitors
• Other active nonAD inflammatory skin diseases or conditions affecting skin
• Medical history including thrombocytopenia, coagulopathy or platelet dysfunction, Q wave interval abnormalities, current or history of certain infections, cancer, lymphoproliferative disorders and other medical conditions at the discretion of the investigator
• Pregnant or breastfeeding women, or women of childbearing potential who are unwilling to use contraception

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Belgium, Brazil, Bulgaria, Canada, Chile, China, Germany, Israel, Italy, Latvia, Mexico, Netherlands, Poland, Romania, Russian Federation, Serbia, Slovakia, Spain, Taiwan, United States

Administrative Information

• NCT Number: NCT03627767
• Other Study ID Numbers: B7451014; JADE REGIMEN ( Other Identifier: Alias Study Number ); 2018-000501-23 ( EudraCT Number ); REGIMEN ( Other Identifier: Alias Study Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: November 2020