Overview

Pilot Study of Ustekinumab for Subjects With Chronic Atopic Dermatitis

Status:
Completed
Trial end date:
2015-03-01
Target enrollment:
0
Participant gender:
All
Summary
Atopic dermatitis (AD) is a chronic disease associated with intense itching, which affects most aspects of everyday life in the majority of patients. Acute inflammation and extensor/facial involvement is common in infants, whereas chronic inflammation increases in prevalence with age, as do localization to flexures. AD has a complex background characterized by immune activation, increased epidermal thickness in chronic diseased skin, and defective barrier function. In normal, healthy skin, the outer layer of the epidermis, the stratum corneum is made up flattened dead cells called corneocytes held together by a mixture of lipids and proteins. The stratum corneum and, in particular, the lipid layer are vital in providing a natural barrier function that locks water inside the skin and keeps allergens and irritants out. In people with AD, the barrier function is defective, which leads to dry skin. As the skin dries out, it cracks allowing allergens and irritants to penetrate. Mild AD can be controlled with emollients and topical medications. However, moderate to severe AD is extremely difficult to control and requires systemic treatment that is often unsatisfactory due to impracticality and lack of effectiveness. Only three therapeutic options exist for moderate to severe AD, including: 1) oral steroids 2) cyclosporine A (CsA), that is not widely used in the US as it is not FDA approved for AD and 3) ultraviolet phototherapy. Oral steroids and CsA treatments have major side effects and UV radiation therapy is highly inconvenient for patients. Several biologic medications, such as TNF-alpha inhibitors, are effective, convenient, and relatively safe therapies for psoriasis, but have thus far not shown efficacy in AD. Ustekinumab is a unique biologic medication that may specifically target AD. The investigators study will determine whether there is a reversal of the skin thickness and the immune pathways involved in the disease during treatment with Ustekinumab and what specific immune cells are involved. The investigators are also interested to understand how the clinical reversal of the disease will correlate with tissue reversal of the disease.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Rockefeller University
Treatments:
Ustekinumab
Criteria
Inclusion Criteria:

- Are male or female and ages 18-75.

- Have moderate to severe AD (as determined using the Objective SCORAD scale ≥15) and a
history of therapeutic failure with at least two of the three different treatment
categories as listed within the inclusion criteria.

- Patients must have tried and failed at least two of the three treatment categories of
the following treatment modalities:

Category 1 : Hydration plus topical steroids and/or antibiotics Category 2: Systemic
Steroids and/or Phototherapy Category 3: Cyclosporine and/or Other Immunomodulators
(Methotrexate, CellCept, Immuran, topical Calcineurin inhibitors)

- Patients who initially respond to cyclosporine but cannot sustain a response after the
drug is discontinued will also be eligible.

- Patients that have contraindications to category 3 drugs will also be allowed to
participate in the study.

- A washout period prior to screening will be required for the following medications:

- Cyclosporine/Oral Steroids/Imuran/Mycophenolate Mofetil/Other systemic
immunosuppressants: 4 weeks

- Phototherapy/Moderate to High Potency Topical Corticosteroids: 2 weeks

- Women of childbearing potential must test negative for pregnancy and be using adequate
birth control measures (e.g., Abstinence, oral contraceptives, intrauterine device,
barrier method with spermicide, or have had a tubal ligation or a hysterectomy) during
the study and for 6 months after receiving the last treatment. Likewise, men capable
of fathering children must also use appropriate methods of birth control (e.g.,
abstinence, barrier methods with spermicide, or have had surgical sterilization such
as vasectomy).

- Patients must be in general good health in the opinion of the investigator.

- Patients with stable chronic asthma, treated with inhaled corticosteroids, will be
eligible.

- The screening laboratory tests must meet the following criteria:

Hemoglobin >9 g/dl WBC count >3.5 x 109 cells/L Neutrophils >1.5 x 109 cells/L Platelets
>100 x 109 cells/L AST/SGOT and ALT/SGPT levels must be within 2 times the upper limit of
normal for the laboratory conducting the test. Alkaline phosphatase levels must be within 2
times the upper limit of normal for the laboratory conducting the test.

- Are PPD negative at the time of screening.

- 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.

Exclusion Criteria:

- Previous treatment with ustekinumab or other agent that specifically targets IL-12 or
23

- Have a history of latent or active granulomatous infection, including TB,
histoplasmosis, or coccidioidomycosis, prior to screening, or are frequently in
contact with individuals who carry active TB infection or a non-tubercular
mycobacterial infection or an opportunistic infection

- Are HIV positive by history or POCT on the screening visit

- Have documented current active hepatitis B (surface antigen positive or asymptomatic
chronic carriers) or 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 any 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. Women of
childbearing age who plan to get pregnant within 15 weeks of stopping study agent