Study Evaluating Efficacy and Safety of PF-04965842 and Dupilumab in Adult Subjects With Moderate to Severe Atopic Dermatitis on Background Topical Therapy

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

• Drug: PF-04965842 100 mg

  PF-04965842 100 mg, administered as two tablets to be taken orally once daily as follows:

  1. 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;
  2. 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.
• Drug: PF-04965842 200 mg

  PF-04965842 200 mg, administered as two tablets to be taken orally once daily as follows:

  1. 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;
  2. 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.
• Drug: Dupilumab
  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.
• Drug: Oral Placebo

  Oral placebo (for PF-04965842) administered as two tablets to be taken orally once daily as follows:

  1. 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;
  2. 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.
• Drug: Injectable Placebo
  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.

• Experimental: PF-04965842 100 mg + Placebo Inj followed by PF-04965842 100mg
  Once-daily oral PF-04965842 100 mg + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral PF-04965842 100 mg from Week 16 to Week 20
  Interventions:

  • Drug: PF-04965842 100 mg
  • Drug: Injectable Placebo
• Experimental: PF-04965842 200 mg + Placebo Inj followed by PF-04965842 200mg
  Once-daily oral PF-04965842 200 mg + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral PF-04965842 200 mg from Week 16 to Week 20
  Interventions:

  • Drug: PF-04965842 200 mg
  • Drug: Injectable Placebo
• Active Comparator: Dupilumab Injection + Oral Placebo followed by Oral Placebo
  Dupilumab injected subcutaneously once every 2 weeks + once-daily oral Placebo from Day 1 until Week 16 followed by once-daily oral Placebo from Week 16 to Week 20
  Interventions:

  • Drug: Dupilumab
  • Drug: Oral Placebo
• Placebo Comparator: Oral Placebo + Placebo Inj followed by 100 mg PF-04965842
  Once-daily oral Placebo + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral 100 mg PF-04965842 from Week 16 to Week 20
  Interventions:

  • Drug: PF-04965842 100 mg
  • Drug: Oral Placebo
  • Drug: Injectable Placebo
• Placebo Comparator: Oral Placebo + Placebo Inj followed by 200 mg PF-04965842
  Once-daily oral Placebo + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral 200 mg PF-04965842 from Week 16 to Week 20
  Interventions:

  • Drug: PF-04965842 200 mg
  • Drug: Oral Placebo
  • Drug: Injectable Placebo

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