Randomized Placebo Controlled Study to Determine Safety, Pharmacodynamics and Efficacy of ILV-094 in Atopic Dermatitis
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|ClinicalTrials.gov Identifier: NCT01941537|
Recruitment Status : Completed
First Posted : September 13, 2013
Results First Posted : May 7, 2019
Last Update Posted : May 7, 2019
|First Submitted Date ICMJE||August 29, 2013|
|First Posted Date ICMJE||September 13, 2013|
|Results First Submitted Date ICMJE||January 10, 2019|
|Results First Posted Date ICMJE||May 7, 2019|
|Last Update Posted Date||May 7, 2019|
|Actual Study Start Date ICMJE||October 2013|
|Actual Primary Completion Date||February 2016 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||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).
|Original Primary Outcome Measures ICMJE
|Change History||Complete list of historical versions of study NCT01941537 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
||Reversal of the pathological epidermal phenotype during ILV-094 therapy [ Time Frame: 12 weeks ]
Reversal of the pathological epidermal phenotype during ILV-094 therapy, and which immune pathways are suppressed during treatment with the drug.
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Randomized Placebo Controlled Study to Determine Safety, Pharmacodynamics and Efficacy of ILV-094 in Atopic Dermatitis|
|Official Title ICMJE||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)|
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).|
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 2|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
|Condition ICMJE||Atopic Dermatitis|
|Study Arms ICMJE||
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE||Same as current|
|Actual Study Completion Date ICMJE||January 2019|
|Actual Primary Completion Date||February 2016 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
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):
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).
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:
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.
|Ages ICMJE||18 Years to 75 Years (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT01941537|
|Other Study ID Numbers ICMJE||JKR-0766|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||
|Responsible Party||Rockefeller University|
|Study Sponsor ICMJE||Rockefeller University|
|Collaborators ICMJE||Icahn School of Medicine at Mount Sinai|
|PRS Account||Rockefeller University|
|Verification Date||January 2019|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP