Pilot Study of Ustekinumab for Subjects With Chronic Atopic Dermatitis

NCT01806662 | Completed Phase 2 Results

• 1 other identifier: JKR-0737
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Atopic Dermatitis

Keywords

Atopic Dermatitis; Eczema

Outcome Measures

Primary Outcomes (1)

• Proportion of SCORAD-50 Response at Week 16.

  Greater improvement from their baseline objective SCORAD (SCORing Atopic Dermatitis) at Week 16. The efficacy variable for each randomized group is the proportion of subjects who achieve an improvement of 50% or greater from their baseline objective SCORAD at Week 16 (at crossover). SCORAD-50 is the percentage of decrease in baseline SCOARD at Week 16. SCORAD is a clinical tool used to assess the extent and severity of eczema. Calculation is based on extent of involvement (skin involvement) and subjective symptoms of itching and loss of sleep. The SCORAD scale ranges from 0 (minimum, lowest possible score, Mild severity) to 103 (maximum, highest possible score, Severe severity) \[last observation carry forward\].

  Week 16

Study Arms (2)

Treatment Arm (Ustekinumab first, Then Placebo)

EXPERIMENTAL

Since there is a crossover design, each patient will be in the treatment arm for 16 weeks of the study.

Drug: Ustekinumab; Other: Placebo

Placebo Arm (Placebo first, Then Ustekinumab)

PLACEBO COMPARATOR

Since there is a crossover design, each patient will be in the placebo arm for 16 weeks of the study. If a patient begins in the placebo arm, they will switch over to the treatment arm at week 16.

Drug: Ustekinumab; Other: Placebo

Interventions

Ustekinumab DRUG

Injection of monoclonal antibody against the p40 subunit of IL-12/23

Also known as: Stelara

Placebo Arm (Placebo first, Then Ustekinumab); Treatment Arm (Ustekinumab first, Then Placebo)

Placebo OTHER

Injection of placebo

Placebo Arm (Placebo first, Then Ustekinumab); Treatment Arm (Ustekinumab first, Then Placebo)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are male or female and ages 18-75.
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Rockefeller University: lead

Study Sites (1)

Rockefeller University

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Dermatitis, Atopic; Eczema

Interventions

Ustekinumab

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: James Krueger
• Organization: Rockefeller University

gilleap@mail.rockefeller.edu

2123278333

Study Officials

• James Krueger, MD PhD

  Rockefeller University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2013
• First Posted: March 7, 2013
• Study Start: March 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: March 14, 2018
• Results First Posted: December 19, 2017

Record last verified: 2018-02

Locations

US (1)