Randomized Placebo Controlled Study to Determine Safety, Pharmacodynamics and Efficacy of ILV-094 in Atopic Dermatitis
Condition: Atopic Dermatitis
MeSH terms: Dermatitis, Atopic; Dermatitis; Eczema
Intervention: ILV-094; Placebo Comparator
Intervention description: IV infusion of ILV-094; Twenty patients will be enrolled in the ILV-094 placebo arm. A loading IV dose of a placebo will be given at baseline (Day 0), followed by five additional IV doses of placebo every two weeks (Weeks 2, 4, 6, 8, and 10).
Intervention MeSH terms: Fezakinumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Atopic Dermatitis

Summary:

      Atopic dermatitis (AD) is a common inflammatory skin disorder that adversely affects most
      aspects of everyday life in majority of patients. It has a prevalence of up to 3-4% of adults
      and up to 25% among children. AD has a complex pathogenesis, characterized by: 1) immune
      activation with increased numbers of T-cells, dendritic cells (DCs), and increased expression
      of inflammatory molecules 2) marked epidermal hyperplasia in chronic diseased skin, and 3)
      defective barrier function with increased trans-epidermal water loss (TEWL) and decreased
      lipids, reflecting underlying alterations in keratinocyte differentiation. AD is
      predominantly a Th2 (IL-4, IL-13, and IL-31) disease, and recently was also found to be a
      "T22" (IL-22) polarized disease.

      ILV-094 is an anti IL-22 antibody and therefore should reverse the immune activation of AD.
      This study is being done to assess the safety, tolerability, clinical efficacy, and mechanism
      of action of ILV-094 in patients with AD.
    

Eligibility criteria:

        -Inclusion Criteria:

        Signed and dated an IRB-approved informed consent form before any study-specific screening
        procedures are performed.

        Male or females between the ages of 18-75 year-old.

        Have moderate to severe AD (as determined using the Objective SCORAD scale ≥30), and an IGA
        index>3).

        Patients who fail or cannot sustain response with one or more of the three treatment
        categories listed below (used for at least 4 weeks):

          -  Category 1: Hydration plus topical steroids and/or antibiotics (tetracycline, bactrim,
             cephalosporins, etc) and or topical immune modulators (protopic/elidel).

          -  Category 2: Systemic Steroids and/or Phototherapy.

          -  Category 3: Cyclosporine and/or Other Immunomodulators (Methotrexate, CellCept, and
             Immuran).

          -  A washout period from cyclosporine and/or oral steroids of 4 weeks and from
             phototherapy of 2 weeks prior to baseline.

          -  A washout period of at least 1 week prior to baseline will also be required for
             patients that responded, but did not sustain response to strong topical steroids (i.e
             clobetasol) or topical immune modulators (i.e Protopic, and Elidel).

          -  The patients will be allowed to use topical therapy during the washout period. These
             will include emollients, and mild steroids (class 6 or 7), except on one target area
             that will be the site for the skin biopsies.

          -  A washout period from any systemic investigational therapy of at least 90 days.

          -  A washout period from cyclosporine and/or oral steroids of 4 weeks and from
             phototherapy of 2 weeks prior to baseline.

          -  A washout period of at least 1 week prior to baseline will also be required for
             patients that responded, but did not sustain response to strong topical steroids (i.e
             clobetasol) or topical immune modulators (i.e protopic, and elidel).

          -  The patients will be allowed to use topical therapy during the washout period. These
             will include emollients, and mild steroids (class 6 or 7), except on one target area
             that will be the site for the skin biopsies.

        Women of childbearing potential must test negative for pregnancy and agree to use birth
        control measures that are highly effective. Highly effective methods are defined as those
        that result in a low failure rate (i.e. less that 1 percent per year abstinence) when used
        consistently and correctly, such as implants, injectables, combined oral contraceptives,
        some intrauterine contraceptive devices (IUD's), sexual abstinence, or a vasectomized
        partner. Likewise, sexually active men must also use appropriate methods of birth control
        (e.g., abstinence, barrier methods with spermicide, or have had surgical sterilization such
        as vasectomy).

        PPD negative at screening.

        Patients with stable chronic asthma, treated with inhaled corticosteroids, will be allowed
        to participate in the study.

        Willingness to avoid alcohol intake 48 hours before each visit in which study drug will be
        received, in order to avoid increases in liver function tests (LFTs) (this was an exclusion
        in other ILV-094 studies in order to guard against increased LFTs due to alcohol intake
        being attributed to study drug).

        -Exclusion Criteria:

        History of active or latent serious infections (TB, or other granulomatous disorders such
        as histoplasmosis, coccidioidomycosis, etc). Skin colonization by Staph. aureus is expected
        in a high percentage of atopic patients with active disease and will not be considered as
        an exclusion criteria.

        *Patients with a history of a positive PPD that have received prophylaxis will be permitted
        to enroll into the study.

        Have a known malignancy or history of malignancy (except for basal or squamous cell
        carcinoma completely excised without evidence of recurrence and treated carcinoma in situ
        of the cervix) or lymphoproliferative diseases such as including lymphoma, or signs and
        symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of
        unusual size or location (e.g. nodes in the posterior triangle of the neck,
        intraclavicular, epitrochlear or periaortic areas) or splenomegaly.

        Have a nontuberculous mycobacterial infection or opportunistic systemic infection (e.g.,
        Pneumocystis carinii, and aspergillosis) within 6 months prior to screening.

        Have positive HIV by history or POCT on the screening visit.

        Have documented current active hepatitis B (surface antigen positive or asymptomatic
        chronic carriers) or a history of hepatitis C infection (anti-HCV positive), by history
        and/or screening test.

        Have a history of substance abuse (drug or alcohol) within the past year before screening.

        Have a serious concomitant illness that could require the use of systemic corticosteroids
        or otherwise interfere with the patient's participation in the trial.

        Pregnant women or women that are breast feeding or plan to breast feed.

        Evidence of acute or unstable clinically significant disease (eg, unstable cardiovascular,
        cerebrovascular, respiratory, renal, or psychiatric disease or any unstable serious
        disorder requiring active frequent monitoring.

        Evidence of other concomitant skin conditions (eg, psoriasis, or lupus erythematosus) other
        than atopic dermatitis that would interfere with evaluations of the effect of study
        medication on atopic dermatitis.

        Have shown a previous immediate hypersensitivity response, including anaphylaxis, to an
        immunoglobulin product (plasma-derived, recombinant, e.g. monoclonal antibody).

        Use of any investigational small molecule drug within 90 days before the first dose of test
        article administration.

        Have a transplanted organ (with the exception of a corneal transplant performed >3 months
        prior to screening).

        Have concomitant autoimmune disease (such as lupus, rheumatoid arthritis, multiple
        sclerosis, Crohn's Disease, etc).

        Clinically important deviation from normal limits in physical examination, vital sign
        measurements, 12-lead electrocardiograms (ECGs), or clinical laboratory tests results, not
        associated with a chronic, well-controlled medical condition. Examples of these

        deviations include following:

          1. Undiagnosed hypertension.

          2. Evidence of undiagnosed ischemic heart disease or potentially

             clinically significant arrhythmia on ECG.

          3. Hemoglobin <9 g/dl

          4. WBC count < 3.5 x 109 cells/L

          5. Neutrophils <1 x 109 cells/L

          6. Platelets < 100 x 109 cells/L

          7. AST/SGOT and ALT/SGPT levels above 2 times the upper limit of normal for the
             laboratory conducting the test.

          8. Alkaline phosphatase levels above 2 times the upper limit of normal for the laboratory
             conducting the test.

        Live vaccines within 3 months before test article administration or during the study.

        Any medical, psychological or social condition that, in the opinion of the investigator,
        would jeopardize the health or well-being of the participant during any study procedures or
        the integrity of the data.