Clinical Trials

Inclusion Criteria:

• Evidence of a personally signed and dated informed consent document indicating that the subject, or his/her legally acceptable representative/parent(s) or legal guardian if a minor, have been informed of all pertinent aspects of the study.
• Male or female subjects of 12 years of age or older, at the time of informed consent  and body weight ≥ 40 kg. Adolescent subjects below the legal age of majority (legal adulthood) in the subject’s country will only be enrolled in this study if instructed by the sponsor and approved by the country’s regulatory/health authority. If these approvals have not been granted, only subjects ≥ the legal age of majority (legal adulthood) in the subject’s country will be enrolled.
• Meet all the following atopic dermatitis criteria:
  • 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 at the screening and baseline visits according to Hanifin and Rajka criteria of AD43;
  • 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.
    • NOTE: Medicated topical therapy is defined as a topical product that contains an active pharmaceutical ingredient indicated for the treatment of AD (irrespective of whether it is an over-the-counter [OTC] or  prescription only product).
  • Moderate to severe AD (affected BSA ≥ 10%, IGA ≥ 3, EASI ≥ 16 and pruritus NRS severity ≥ 4 on the day of the baseline visit).
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
• Female subjects who are of child-bearing potential (which includes adolescents aged 12 years and older regardless of whether they have experienced menarche) must not be intending to become pregnant, currently pregnant, or lactating. The following conditions apply:
  • Female subjects of childbearing potential must have a confirmed negative pregnancy test prior to treatment with investigational product;
  • 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.
    • NOTE: Sexual abstinence, defined as completely and persistently refraining from all heterosexual intercourse (including during the entire period of risk associated with study treatments) may obviate the need for contraception ONLY if this is the preferred and usual lifestyle of the subject.
• 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.
• Must agree to avoid prolonged exposure to the sun and not to use tanning booths, sun lamps or other ultraviolet light sources during 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.
• Any psychiatric condition including recent or active suicidal ideation or behavior that meets any of the following criteria:
  • Suicidal ideation associated with actual intent and a method or plan in the past year: “Yes” answers on items 4 or 5 of the Columbia suicide severity rating scale (C-SSRS) (Appendix 15);
  • Previous history of suicidal behaviors in the past 5 years: “Yes” answer (for events that occurred in the past 5 years) to any of the suicidal behavior items of the C-SSRS;
  • Any lifetime history of serious or recurrent suicidal behavior;
  • Suicidal behaviors questionnaire – revised (SBQ-R) total score ≥ 8;
  • Clinically significant depression: patient health questionnaire – 8 items (PHQ-8) total score ≥ 15;
  • The presence of any current major psychiatric disorder that is not explicitly permitted in the inclusion/exclusion criteria;
  • In the opinion of the investigator or Pfizer (or designee) exclusion is required.
• A current or past medical history of conditions associated with thrombocytopenia, coagulopathy or platelet dysfunction.
• Receiving anti-coagulants or medications known to cause thrombocytopenia (unless considered safe to stop and washout for the duration of the study).
• Currently have active forms of other inflammatory skin diseases, ie, not AD or have evidence of skin conditions (eg, psoriasis, seborrheic dermatitis, Lupus) at the time of Day 1 that would interfere with evaluation of atopic dermatitis or response to treatment.
• Vaccinated or exposed to a live or attenuated vaccine within the 6 weeks prior to the first dose of investigational product, or is expected to be vaccinated or to have household exposure to these vaccines during treatment or during the 6 weeks following discontinuation of investigational product.
• Adolescent subjects 12 to <18 years old without documented evidence of having received at least one dose of the varicella vaccine in countries where the vaccine is approved and standard of care or those who do not have evidence of prior exposure to varicella zoster virus (VZV) based on serological testing (i.e., varicella zoster virus immunoglobulin G antibody [VZV IgG Ab]) at screening.
• Subjects who have received prior treatment with any JAK inhibitors.
• Participation in other studies involving investigational drug(s) within 8 weeks or within 5 half-lives (if known) whichever is longer, prior to study entry and/or during study participation.
  • Note: Any investigational or experimental therapy taken or procedure performed for AD, psoriasis, psoriatic arthritis or rheumatoid arthritis in the previous 1 year should be discussed with the Pfizer Medical Monitor (or designee). Subjects cannot participate in studies of other investigational or experimental therapies or procedures at any time during their participation in this study.
• Have received any of the following treatment regimens specified in the timeframes outlined below:
  • Within 1 year of first dose of investigational product:
    • Prior treatment with non B cell-specific lymphocyte depleting agents/therapies (e.g., alemtuzumab [CAMPATH®], alkylating agents [eg, cyclophosphamide or chlorambucil], total lymphoid irradiation, etc.). Subjects who have received rituximab or other selective B lymphocyte depleting agents (including experimental agents) are eligible if they have not received such therapy for at least 1 year prior to study baseline and have normal cluster of differentiation (CD) 19/20+ counts by fluorescence-activated cell sorting (FACS) analysis.
  • Within 12 weeks of first dose of investigational product:
    •  Other biologics: within 12 weeks of first dose of investigational product or 5 half-lives (if known), whichever is longer.
  • Within 6 weeks of first dose of investigational product:
    • Use of dupilumab.
  • Within 4 weeks of first dose of investigational product:
    • Use of oral immunosuppressive drugs (e.g., cyclosporin A [CsA], azathioprine, methotrexate, systemic corticosteroids, mycophenolate-mofetil, IFN-y) within 4 weeks of first dose of investigational product or within 5 half-lives (if known), whichever is longer;
    • Phototherapy narrowband UVB (NB-UVB) or broad band phototherapy;
    • Regular use (more than 2 visits per week) of a tanning booth/parlor;
    • Herbal medications with unknown properties or known beneficial effects for AD.
  • Within 1 week of first dose of investigational product:
    • Anti-platelet drugs.
  • Note: low dose acetyl salicylic acid (≤ 100 mg QD) is permitted, for the purpose of cardiovascular prophylaxis, at the discretion of the investigator.
  • Within 72 hours of first dose of investigational product:
    • Topical treatments that could affect atopic dermatitis (e.g., corticosteroids, calcineurin inhibitors, tars, antibiotic creams, topical antihistamines).
  • Note: Corticosteroid inhalers and intranasal sprays are allowed for stable asthma and/or allergic rhinitis patients.
• Have a history of any lymphoproliferative disorder such as Epstein Barr Virus (EBV) related lymphoproliferative disorder, history of lymphoma, leukemia, or signs or symptoms suggestive of current lymphatic or lymphoid disease.
• Infection History:
  • Have a history of systemic infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator within 6 months prior to Day 1;
  • Have active chronic or acute skin infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks prior to Day 1, or superficial skin infections within 1 week prior to Day 1;
  • A subject known to be infected with Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C;
  • Have a history (single episode) of disseminated herpes zoster or disseminated herpes simplex, or a recurrent (more than one episode of) localized, dermatomal herpes zoster.
• Have a history of alcohol or substance abuse within 6 months prior to Day 1 that in the opinion of the investigator will preclude participation in the study.
• A Screening 12-lead ECG that demonstrates clinically significant abnormalities requiring treatment (e.g., acute myocardial infarction, serious tachy- or brady-arrhythmias) or that are indicative of serious underlying heart disease (e.g., cardiomyopathy, major congenital heart disease, low voltage in all leads, Wolff-Parkinson-White syndrome) or criteria associated with Q wave interval (QT)/Fridericia-corrected Q wave (QTcF) abnormalities including:
  • A marked prolongation of QTcF interval (>450 milliseconds [ms]) on the screening ECG;
  • A history of additional risk factors for Torsade de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome);
  • Use of concomitant medications that prolong the QT/QTcF interval.
• Have a known immunodeficiency disorder or a first-degree relative with a hereditary immunodeficiency.
• Have any malignancies or have a history of malignancies with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin, or cervical carcinoma in situ.
• Require treatment with prohibited concomitant medication(s) or have received a prohibited concomitant medication within the specified time frame prior to the first dose of study medication.
• Have evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB) as evidenced by any of the following:
  • A positive QuantiFERON®-TB Gold (QFT-G) In-Tube test or positive Mantoux/Purified Protein Derivative (PPD) tuberculin skin test performed at or within the 12 weeks prior to Day 1.
  • It is recommended that subjects with a history of Bacille Calmette Guérin (BCG) vaccination be tested with the QFT-G test since the Mantoux/PPD tuberculin skin test may be positive due to vaccination. 
  • A negative QFT-G or Mantoux/PPD tuberculin skin test is required unless the subject has previously received a documented adequate course of therapy for either latent (9 months of isoniazid in a locale where rates of primary multi-drug TB resistance are <5% or an acceptable alternative regimen) or active (acceptable multi-drug regimen) TB infection. If the current incidence rates of multi-drug resistant TB infection in the locale are unavailable, an adequate treatment regimen should be defined as the regimen recommended by the health ministry or expert panel in the locale;
  • Chest radiograph (or chest Computed Tomography (CT) scan, if available) taken at screening with changes suggestive of active tuberculosis (TB) infection as determined by a qualified radiologist. A chest X-ray is required for adults and recommended for adolescents per local standard/guidelines, unless previously performed and documented within 12 weeks prior to Study Day 1.
  • A history of either untreated or inadequately treated latent or active TB infection;
  • A subject who is currently being treated for active TB infection is to be excluded.
• ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat, if deemed necessary:
  • Absolute neutrophil count of <1.2 x 109/L (<1200/mm3);
  • Hemoglobin <10.0 g/dL or hematocrit <30%;
  • Platelet count of <150 x 109/L (<150,000/mm3);
  • Absolute lymphocyte count of <0.50 x 109 /L (<500/mm3);
  • Estimated Creatinine Clearance <40 mL/min based on the age appropriate calculation, or serum creatinine >1.5 times the upper limit of normal (ULN);
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values >2 times the ULN;
  • Total bilirubin ≥ 1.5 times the ULN; subjects with a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is ≤ ULN.
• In the opinion of the investigator or sponsor, have any uncontrolled clinically significant laboratory abnormality that would affect interpretation of study data or the subject’s participation in the study.
• Have undergone significant trauma or major surgery within 1 month of the first dose of investigational product.
• Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study.
• Have known hypersensitivity to PF-04965842 or to any of the excipients of the study drug.