A Randomized Placebo-controlled Study to Determine the Safety, Tolerability, Pharmacodynamics and Clinical Efficacy of ILV-094 (an IL-22 Antibody) Administered Intravenously to Subjects With Atopic Dermatitis (AD)
Overview
- Phase
- Phase 2
- Intervention
- ILV-094
- Conditions
- Atopic Dermatitis
- Sponsor
- Rockefeller University
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Percentage Change in SCORAD
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief 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.
Detailed Description
This is a randomized, double-blind, placebo-controlled, study of six IV infusions of ILV-094 administered to subjects with atopic dermatitis. Sixty subjects will be randomly assigned in a 2:1 ratio to one of the two treatments arms (ILV-094 vs placebo). Forty patients will be enrolled in the ILV-094 treatment arm and 20 in the placebo-treatment arm, accordingly. A loading IV dose of 600 mg of ILV-094 or placebo will be given at baseline (Day 0), followed by five additional IV doses of 300 mg of ILV-094 or placebo every two weeks (Weeks 2, 4, 6, 8, and 10). We will continue to follow the patients every two weeks for an additional 10 weeks after the last IV dose (20 weeks post baseline).
Investigators
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.
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.
Arms & Interventions
ILV-094
Forty patients will be enrolled in the ILV-094 treatment arm. A loading IV dose of 600 mg of ILV-094 will be given at baseline (Day 0), followed by five additional IV doses of 300 mg of ILV-094 every two weeks (Weeks 2, 4, 6, 8, and 10).
Intervention: ILV-094
Placebo comparator
Twenty patients will be enrolled in the ILV-094 placebo arm. A loading IV dose of 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: Placebo Comparator
Outcomes
Primary Outcomes
Percentage Change in SCORAD
Time Frame: 12 weeks
Percentage Change in the Scoring of Atopic Dermatitis (SCORAD) at week 12 compared to baseline in both arms of the study in subjects with atopic dermatitis. SCORAD (Severity scoring of Atopic Dermatitis) is composite severity index comprising a) the amount/extent of body surface area affected, b) subjective symptom visual analog assessments \[itchy 0 (no itching) to 3 (severe itching) and sleep disturbance 0(no sleep disturbance) to 3 (severe sleep disturbance)\], and c) 6 disease intensity assessments \[dryness/scaling, erythema, induration/papulation, excoriation, lichenification and oozing/weeping/crusting, each graded from 0 to (none) to 3 (severe). A SCORAD score ranges from 0 (no AD present) to 103 (severe).
Secondary Outcomes
- The Percentage of Patients Who Achieve an Improvement of 50% or Greater From Their Baseline Objective SCORAD at Week 12 of ILV-094 Treatment(12 weeks)
- Change in IGA Score(12 weeks)
- The (Per-patient) Percent Improvement in the SCORAD Relative to Baseline.(12 weeks)