Efficacy and Safety Study of Mepolizumab in Subjects With Moderate to Severe Atopic Dermatitis
Condition: Dermatitis, Atopic
MeSH terms: Dermatitis, Atopic; Dermatitis; Eczema
Intervention: Mepolizumab 100 mg; Placebo matching mepolizumab
Intervention description: Mepolizumab is available as lyophilized powder in sterile vials for injection. The content is reconstituted with 1.2 milliliter (mL) Sterile Water just prior to use. Subjects will receive 1mL (100 mg/mL) bolus subcutaneous injections.; Placebo is available as 0.9% sodium chloride solution. Subjects will receive 1mL bolus subcutaneous injections.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: subcutaneous; safety; mepolizumab; efficacy; atopic dermatitis

Summary:

      Mepolizumab is a humanized Immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that acts on
      Interleukin-5 (IL-5), which is responsible for the growth and differentiation, recruitment,
      activation, and survival of eosinophils; thereby reducing the production and survival of
      eosinophils which may be therapeutic in subjects with atopic dermatitis (AD). This study will
      investigate the efficacy and safety of mepolizumab (100 milligram [mg] subcutaneous [SC]
      administered every 4 weeks) compared with placebo in adult subjects with moderate to severe
      atopic dermatitis (AD). Subjects will be randomized 1:1 to either placebo SC or mepolizumab
      SC. The study will comprise of a pre-screening period of up to approximately 4 weeks, a
      screening period of up to 2 weeks, followed by a 16-Week study treatment period (16 weeks
      with the last dose of study treatment at Week 12) and follow-up period of up to 4-week. The
      total duration of subject participation will be approximately 26 weeks. (Note: For subjects,
      who may need to stop treatment with a biologic, the total Pre-Screening and Screening period
      may last up to 20 weeks and total duration of participation in the study may be up to 40
      weeks).
    

Eligibility criteria:

        Inclusion Criteria

          -  Age between 18 and 70 years of age inclusive, at the time of signing the informed
             consent.

          -  AD diagnosed by the Eichenfield revised criteria of Hanifin and Rajka.

          -  Diagnosis of AD >=2 years prior to the Screening visit.

          -  An IGA score >=3 at the Screening and Baseline visits.

          -  AD involvement of >=10% body surface area at the Screening and Baseline visits.

          -  EASI score >=16 at the Screening and Baseline visits.

          -  Absolute blood eosinophil count >=350 cells/microliter at the Screening visit.

          -  Applied the same non-prescription, non-medicated (without an active ingredient)
             emollient twice daily for at least 7 days immediately before the Baseline visit.

          -  Recent history (<=6 months prior to the Screening visit) of inadequate response to a
             stable regimen of prescription topical medication or for whom prescription topical
             medications are not tolerated or where there is a concern for potential side effects,
             such as skin thinning or increased risk of hypothalamic-pituitary-adrenal [HPA]
             suppression; as well as, inadequate response to optimization of non-pharmacological
             measures such as moisturizers. Inadequate response to a stable regimen of prescription
             topical medication (such as medium to high potency topical corticosteroids or topical
             calcineurin inhibitors) is defined as failure to achieve and maintain remission or low
             disease activity state (equivalent to an IGA score =0 [clear] to 2 [mild]) despite
             treatment for the recommended duration as per label or for the maximum duration
             recommended for the subject treatment, whichever is shorter.

          -  Male or female: A female subject is eligible to participate if she is not pregnant (as
             confirmed by a negative urine human chorionic gonadotrophin (hCG) test), not
             lactating, and at least one of the following conditions: Non-reproductive potential-
             Pre-menopausal females with documented tubal ligation, documented hysteroscopic tubal
             occlusion procedure with follow-up confirmation of bilateral tubal occlusion,
             hysterectomy, documented bilateral oophorectomy; and postmenopausal defined as 12
             months of spontaneous amenorrhea (in questionable cases a blood sample with
             simultaneous follicle stimulating hormone [FSH] and estradiol levels consistent with
             menopause). Females on hormone replacement therapy (HRT) and whose menopausal status
             is in doubt will be required to use one of the highly effective contraception methods
             if they wish to continue their HRT during the study. Otherwise, they must discontinue
             HRT to allow confirmation of post-menopausal status prior to study enrolment.
             Reproductive potential and agrees to follow one of the options listed in the Modified
             List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive
             Potential (FRP) from 30 days prior to the first dose of study medication and until 16
             weeks after the last dose of study medication.

          -  The investigator is responsible for ensuring that subjects understand how to properly
             use these methods of contraception.

          -  Subject is able to give signed informed consent that includes compliance with the
             requirements and restrictions listed in the consent form and in this protocol.

        Exclusion Criteria

          -  Other types of eczema.

          -  Any other concomitant skin disorder (e.g., generalized erythroderma such as
             Netherton's Syndrome, or psoriasis), pigmentation, or extensive scarring that in the
             opinion of the investigator may interfere with the evaluation of AD lesions or
             compromise subject safety.

          -  Immunocompromised (e.g., lymphoma, acquired immunodeficiency syndrome, Wiskott-Aldrich
             Syndrome) or has a history of malignant disease within 5 years before the Baseline
             visit. Note: Subjects with successfully treated basal cell carcinoma (no more than 3
             lesions), squamous cell carcinoma of the skin, or cervical carcinoma in situ, with no
             evidence of recurrence within the 3 years prior to the Baseline visit may participate
             in the study.

          -  A positive history for human immunodeficiency virus (HIV) antibody.

          -  Chronic or acute infection requiring treatment with oral or intravenous (IV)
             antibiotics, antivirals, anti-protozoals, or antifungals within 4 weeks before the
             Screening visit or anytime between the Screening and Baseline visits.

          -  Superficial skin infections within 1 week before the Screening visit.

          -  Known, pre-existing or suspected parasitic infection within 6 months before the
             Screening visit.

          -  Other known or suspected conditions that could lead to elevated eosinophils, for
             example, hypereosinophilic syndromes including eosinophilic granulomatosis with
             polyangiitis (EGPA, also known as Churg-Strauss Syndrome), eosinophilic esophagitis,
             or severe asthma.

          -  A history or ongoing serious illness or medical, physical, or psychiatric condition(s)
             that, in the investigator's opinion, may interfere with the subject's completion of
             the study.

          -  ALT >2x upper limit of normal (ULN)

          -  Bilirubin >1.5x ULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is
             fractionated and direct bilirubin <35%).

          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).

          -  QT Interval Corrected by Fridericia Correction Formula (QTcF) >450 milliseconds (msec)
             or QTcF >480 msec in subjects with Bundle Branch Block.

          -  Clinically significant abnormality in the hematological or biochemical screen, as
             judged by the investigator.

          -  Previously treated with mepolizumab or participated in a previous mepolizumab clinical
             study.

          -  Prior treatment with any of the medications or treatments listed in Table 1 within the
             indicated periods before the Screening visit.

          -  Prolonged exposure to natural (e.g, sunlight) ultraviolet (UV) radiation within 4
             weeks prior to the Baseline visit and/or intention to have such exposure during the
             study, which is thought by the investigator to potentially impact the subject's AD.

          -  More than 2 visits per week to a tanning booth or parlor in the 4 weeks prior to the
             Baseline visit.

          -  Onset of a new exercise routine or major change to a previous exercise routine within
             2 weeks before randomization, or unwilling to maintain current level of physical
             activity throughout the length of participation in this study.

          -  History of alcohol or other substance abuse within the last 2 years.

          -  Hypersensitivity to mepolizumab or any of its excipients.

          -  Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test
             result at screening or within 3 months prior to first dose of study treatment.

          -  Exposure to more than 4 investigational medicinal products within 12 months prior to
             the Baseline visit.

          -  Subject is a member of the investigational team or his/her immediate family.