A Dose Ranging Placebo-Controlled Double-Blind Study to Evaluate the Safety and Efficacy of Tezepelumab in Atopic Dermatitis
Condition: Atopic Dermatitis
MeSH terms: Dermatitis, Atopic; Dermatitis; Eczema
Intervention: Tezepelumab; Placebo
Intervention description: Solution for injection; Placebo solution for injection
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This phase 2b study is designed to evaluate the safety and efficacy of tezepelumab as a monotherapy and explore its efficacy as adjunct therapy in subjects with moderate-to-severe AD. This study consists of Part A (the main study evaluating tezepelumab as a monotherapy) and Part B (a study evaluating tezepelumab as adjunctive therapy when combined with a topical corticosteroid regimen
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 251.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Atopic Dermatitis; eczema; tezepelumab; dermatology; dermatitis; inflammation; skin; moderate dermatitis; severe dermatitis

Summary:

      This phase 2b study is designed to evaluate the safety and efficacy of tezepelumab as a
      monotherapy and explore its efficacy as adjunct therapy in subjects with moderate-to-severe
      atopic dermatitis (AD).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject has provided informed consent prior to initiation of any study specific
             activities/procedures.

          -  Age greater than or equal to 18 to less than or equal to 75 years at screening.

          -  Clinical diagnosis of chronic AD (also known as atopic eczema) for at least 2 years
             prior to screening and has confirmed AD (Hanifin and Rajka criteria for AD (Hanifin
             and Rajka, 1980).

          -  AD that affects greater than or equal to' 10% body surface area as assessed by EASI at
             screening and on day 1.

          -  An IGA score of greater than or equal to 3 at screening and on day 1.

          -  An EASI score of greater than or equal to 16 at screening and on day 1.

          -  Subject discontinued treatment with TCS, topical calcineurin inhibitors (TCI), and
             prescription moisturizers containing TCS or topical calcineurin inhibitors (TCI) for
             at least the 7 days immediately prior to the first dose of investigational product

          -  Documented recent history (within 12 months before the screening visit) of inadequate
             response totreatment with topical TCS or subjects for whom topical treatments are
             otherwise medically inadvisable (ie, because of important side effects or safety
             risks).

               -  Inadequate response is defined as failure to achieve and maintain remission or a
                  low disease activity state (comparable to IGA 0 = clear to IGA 2 = mild) despite
                  treatment with a daily regimen of TCS of medium or higher potency (with or
                  without TCI as appropriate).

        Exclusion Criteria:

          -  Active dermatologic conditions, which might confound the diagnosis of AD or would
             interfere with the assessment of treatment, such as scabies, seborrheic dermatitis,
             cutaneous lymphoma, ichthyosis, psoriasis, allergic contact dermatitis, or irritant
             contact dermatitis.

          -  History of a clinically significant infection within 28 days prior to day 1 that, in
             the opinion of the investigator or medical monitor, might compromise the safety of the
             subject in the study, interfere with evaluation of the investigational product, or
             reduce the subject's ability to participate in the study. Clinically significant
             infections are defined as either of the following: 1) a systemic infection; or 2) a
             serious skin infection requiring parenteral antibiotic, antiviral, or antifungal
             medication.

          -  Diagnosis of a helminth parasitic infection within 6 months prior to screening that
             had not been treated with or had failed to respond to standard of care therapy.

          -  Documented medical history of chronic alcohol or drug abuse within 12 months prior to
             screening.

          -  History of anaphylaxis following any biologic therapy.

          -  Evidence of active liver disease at screening, including jaundice or aspartate
             aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase
             greater than twice the upper limit of normal (ULN).

          -  Subjects who, in the opinion of the investigator, have evidence of active tuberculosis
             (TB), either treated or untreated, or a positive QuantiFERON-tuberculosis Gold (QFT-G)
             test for TB during screening. Subjects with an indeterminate QFT-G may be enrolled if
             they have ALL of the following:

               -  No symptoms of TB: productive, prolonged cough (> 3 weeks); coughing up blood;
                  fever; night sweats; unexplained appetite loss; unintentional weight loss

               -  No evidence of active TB on chest radiograph within 3 months prior to the first
                  dose of investigational product. Note: Chest radiograph is not part of screening
                  procedure and will be the responsibility

          -  Positive hepatitis B surface antigen or hepatitis C antibody serology. Subjects with a
             history of hepatitis B vaccination without a history of hepatitis B are allowed to
             enroll in the study.

          -  Positive human immunodeficiency virus (HIV) test at screening or the subject is taking
             antiretroviral medications, as determined by medical history, prior medications,
             and/or the subject's verbal report.

          -  Other Medical Conditions>

          -  History of malignancy, except for basal cell carcinoma or in situ carcinoma of the
             cervix treated with apparent success with curative therapy ≥ 12 months prior to
             screening or other malignancies treated with apparent success with curative therapy ≥
             5 years prior to screening.

          -  History or evidence of severe depression, schizophrenia, previous suicide attempts, or
             suicidal ideation.

        Prior/Concomitant Therapy:

          -  Subjects who are unwilling to abstain from the use of TCS, TCI, and prescription
             moisturizers (those that contain TCS and TCI) from screening through week 16 (applies
             only to Part A subjects)

          -  Subjects who have had side effects of topical medications including intolerance to
             treatment, hypersensitivity reactions, significant skin atrophy, or systemic effects
             as assessed by the investigator or by the subject's treating physician (applies only
             to Part B subjects)

          -  More than or equal to 30% of the total lesional surface is located on areas of thin
             skin that cannot be safely treated with medium or higher potency TCS (eg, face, neck,
             intertriginous areas, areas of skin atrophy) (applies only to Part B subjects)

          -  Receipt of any approved biologic agent (eg, dupilumab) within 4 months or 5
             elimination half-lives (whichever is longer) prior to screening

          -  Have used immunosuppressive/immunomodulating drugs (eg, systemic corticosteroids,
             cyclosporine, mycophenolate-mofetil, interferon (IFN)-gamma, Janus kinase inhibitors,
             azathioprine, methotrexate) within 4 weeks prior to screening, or any condition that,
             in the opinion of the investigator, is likely to require such treatment(s) during the
             first 4 weeks of study treatment.

          -  Have had phototherapy for AD in the 2 months prior to day 1, and subjects unwilling to
             avoid phototherapy during the first 16 weeks of the study

          -  If on allergen-specific immunotherapy, subjects must be on a maintenance dose and
             schedule for ≥ 28 days prior to screening. Allergen-specific immunotherapy is defined
             as SC immunotherapy to aeroallergens and/o venom (Hymenoptera) as well as sublingual
             immunotherapy to aeroallergens

          -  Vaccination with a live or attenuated vaccine within 28 days prior to day 1. Receipt
             of inactive/killed vaccinations (eg, inactive influenza) is allowed. Note that receipt
             of the Th2 cytokine inhibitor suplatast within 15 days prior to randomization and
             during the study is not allowed.

          -  Major surgery within 8 weeks prior to screening or planned inpatient surgery or
             hospitalization during the study period

          -  Currently receiving treatment in another investigational device or drug study, or less
             than 6 months since ending treatment on another investigational device or drug
             study(ies). Other investigational procedures while participating in this study are
             excluded.

        Other Exclusions:

          -  Female subject is pregnant or breastfeeding or planning to become pregnant or
             breastfeed during treatment and for an additional 16 weeks after the last dose of
             investigational product. (Females of childbearing potential should only be enrolled in
             the study after a negative highly sensitive serum pregnancy test).

          -  Female subjects of childbearing potential who are sexually active with unsterilized
             male partners unwilling to use 1 highly effective method of contraception during
             treatment and for an additional 16 weeks after the last dose of investigational
             product. Cessation of contraception after this point must be discussed with a
             responsible physician. Females of childbearing potential are defined as those who are
             not surgically sterile (ie, had bilateral tubal ligation, bilateral oophorectomy, or
             complete hysterectomy) or postmenopausal (defined as 12 months with no menses without
             an alternative medical cause). A highly effective method of contraception is defined
             as one that resulted in a low failure rate (ie, < 1% per year) when used consistently
             and correctly.

          -  Subject has known sensitivity to any of the products or components to be administered
             during dosing.

          -  History or evidence of any other clinically significant disorder, condition or disease
             (with the exception of those outlined above) that, in the opinion of the investigator
             or Amgen physician, if consulted, would pose a risk to subject safety or interfere
             with the study evaluation, procedures, or completion.