Randomized Placebo Controlled Study to Determine Safety, Pharmacodynamics and Efficacy of ILV-094 in Atopic Dermatitis

NCT01941537 | Completed Phase 2 Results DMC

• 1 other identifier: JKR-0766
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Atopic Dermatitis

Keywords

Atopic Dermatitis

Outcome Measures

Primary Outcomes (1)

• Percentage Change in SCORAD

  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).

  12 weeks

Secondary Outcomes (3)

• 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

• The (Per-patient) Percent Improvement in the SCORAD Relative to Baseline.

  12 weeks

• Change in IGA Score

  12 weeks

Study Arms (2)

ILV-094

EXPERIMENTAL

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).

Drug: ILV-094

Placebo comparator

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).

Drug: Placebo Comparator

Interventions

ILV-094 DRUG

IV infusion of ILV-094

ILV-094

Placebo Comparator DRUG

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).

Also known as: Placebo

Placebo comparator

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• \*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

Sponsors & Collaborators

• Rockefeller University: lead
• Icahn School of Medicine at Mount Sinai: collaborator

Study Sites (1)

The Rockefeller University

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Dermatitis, Atopic

Interventions

fezakinumab

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

Results Point of Contact

• Title: James Krueger
• Organization: Rockefeller University

kruegej@rockefeller.edu

2123277730

Study Officials

• James Krueger, MD

  The Rockefeller University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: August 29, 2013
• First Posted: September 13, 2013
• Study Start: October 1, 2013
• Primary Completion: February 1, 2016
• Study Completion: January 1, 2019
• Last Updated: May 7, 2019
• Results First Posted: May 7, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)