Study Evaluating Efficacy and Safety of PF-04965842 and Dupilumab in Adult Subjects With Moderate to Severe Atopic Dermatitis on Background Topical Therapy
Condition: Dermatitis; Dermatitis, Atopic; Eczema; Skin Diseases; Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin Diseases, Eczematous; Hypersensitivity; Hypersensitivity, Immediate; Immune System Diseases
MeSH terms: Dermatitis, Atopic; Genetic Diseases, Inborn; Skin Diseases, Genetic; Dermatitis; Eczema; Skin Diseases; Skin Diseases, Eczematous; Hypersensitivity; Immune System Diseases; Hypersensitivity, Immediate
Intervention: PF-04965842 100 mg; PF-04965842 200 mg; Dupilumab; Oral Placebo; Injectable Placebo
Intervention description: PF-04965842 100 mg, administered as two tablets to be taken orally once daily as follows:
In the arm "PF-04965842 100 mg + Injectable Placebo followed by PF-04965842 100 mg," PF-04965842 100 mg is taken together with Injectable Placebo from Day 1 until Week 16, then by itself from Week 16 to Week 20;
In the arm "Oral Placebo + Injectable Placebo followed by 100 mg PF-04965842" subjects take PF-04965842 100 mg from Week 16 to Week 20.; PF-04965842 200 mg, administered as two tablets to be taken orally once daily as follows:
In the arm "PF-04965842 200 mg + Injectable Placebo followed by PF-04965842 100 mg," PF-04965842 200 mg is taken together with Injectable Placebo from Day 1 until Week 16, then by itself from Week 16 to Week 20;
In the arm "Oral Placebo + Injectable Placebo followed by 200 mg PF-04965842" subjects take PF-04965842 200 mg from Week 16 to Week 20.; Two subcutaneous injections of Dupilumab 300 mg as a loading dose administered on Day 1 (for a total of 600 mg) followed by one injection once every two weeks (q2w) until Week 16.; Oral placebo (for PF-04965842) administered as two tablets to be taken orally once daily as follows:
In the arm "Dupilumab Injection + Oral Placebo followed by Oral Placebo," the Oral Placebo is taken together with Dupilumab from Day 1 until Week 16, then by itself to Week 20;
In the arms "Oral Placebo + Injectable Placebo followed by 100 mg PF-04965842" and "Oral Placebo + Injectable Placebo followed by 200 mg PF-04965842," subjects, take Oral Placebo from Day 1 until Week 16.; Two subcutaneous injections of Placebo (for Dupilumab) administered as a loading dose on Day 1 followed by one injection every other week (q2w) until Week 16.
Intervention MeSH terms: Abrocitinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 838.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: atopic dermatitis; atopic eczema; eczema; JAK; janus kinase

Summary:

      B7451029 is a Phase 3 study to investigate PF-04965842 in adult patients who have moderate to
      severe atopic dermatitis and use background topical therapy. The efficacy of two dosage
      strengths of PF-04965842, 100 mg and 200 mg taken orally once daily will be evaluated
      relative to placebo over 12 weeks. The efficacy of the two dosage strengths of PF-04965842
      will be compared with dupilumab in terms of pruritus relief at 2 weeks. The two dosage
      strengths of PF-04965842 and dupilumab 300 mg injected subcutaneously once every two weeks
      (with a loading dose of 600 mg injected on the first day) will also be evaluated relative to
      placebo over 16 weeks. The safety of the investigational products will be evaluated over the
      duration of the study. Subjects will use non-medicated emollient at least twice a day and
      medicated topical therapy such as corticosteroids, calcineurin inhibitors or PDE4 inhibitors,
      as per protocol guidance, to treat active lesions during the study. Subjects who are
      randomized to receive one of the two dosage strengths of PF-04965842 will also receive
      placebo injectable study drug every two weeks until Week 16 and then will continue on
      receiving only the oral study drug for 4 weeks. Subjects who are randomized to receive
      dupilumab injections every two weeks will also receive oral placebo to be taken once daily
      until Week 16 and will then continue to receive only the oral placebo for 4 weeks. Subjects
      who are randomized to the placebo arms, will receive both daily oral placebo and injectable
      placebo every two weeks until Week 16, after which they will receive either 100 mg or 200 mg
      of PF-04965842 taken orally once daily for 4 weeks, dependent upon which arm they have been
      allocated to. Eligible subjects will have an option to enter a long-term extension study
      after completing 20 weeks of treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female subjects aged 18 years or older at the time of informed consent

          -  Diagnosis of atopic dermatitis (AD) for at least 1 year and current status of moderate
             to severe disease (>= the following scores: BSA 10%, IGA 3, EASI 16, Pruritus NRS
             severity 4)

          -  Documented recent history (within 6 months before the screening visit) of inadequate
             response to treatment with medicated topical therapy for AD for at least 4 weeks, or
             who have required systemic therapies for control of their disease.

          -  Must be willing and able to comply with standardized background topical therapy, as
             per protocol guidelines throughout the study

          -  Female subjects who are of childbearing potential must not be intending to become
             pregnant, currently pregnant, or lactating. The following conditions apply:

               1. Female subjects of childbearing potential must have a confirmed negative
                  pregnancy test prior to randomization;

               2. Female subjects 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 investigational product.

          -  Female subjects of non-childbearing potential must meet at least 1 of the following
             criteria:

               -  Have undergone a documented hysterectomy and/or bilateral oophorectomy;

               -  Have medically confirmed ovarian failure; or

               -  Achieved postmenopausal status, defined as follows: cessation of regular menses
                  for at least 12 consecutive months with no alternative pathological or
                  physiological cause and have a serum follicle stimulating hormone (FSH) level
                  confirming the postmenopausal state.

        All other female subjects (including female subjects with tubal ligations) are considered
        to be of childbearing potential.

        -If receiving concomitant medications for any reason other than AD, must be on a stable
        regimen prior to Day 1 and through the duration of the study

        Exclusion Criteria:

          -  Other acute or chronic medical or psychiatric condition including recent (within the
             past year) or active suicidal ideation or behavior or laboratory abnormality that may
             increase the risk associated with study participation or investigational product
             administration or may interfere with the interpretation of study results and, in the
             judgment of the investigator, would make the subject inappropriate for entry into this
             study

          -  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

          -  Unwilling to discontinue current AD medications prior to the study or require
             treatment with prohibited medications during the study

          -  Other active nonAD inflammatory skin diseases or conditions affecting skin

          -  Prior treatment with JAK inhibitors

          -  Previous treatment with dupilumab

          -  Unwilling to discontinue current AD medications prior to the study or require
             treatment with prohibited medications during the study