Atopic Dermatitis
Conditions
Keywords
Atopic Dermatitis
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).
Interventions
DRUGILV-094
IV infusion of ILV-094
DRUGPlacebo Comparator
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).
Sponsors
Icahn School of Medicine at Mount Sinai
Rockefeller University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion 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. * 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). 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). -
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in SCORAD | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 SCORAD50 captures individuals who achieved 50% or greater improvement from baseline SCORAD score. This outcome measure is the percentage of participants who achieved SCORAD50 at week 12. This analysis will be performed using fisher exact test. Patients who drop-out will be considered treatment failures (non-responder approach). A sensitivity analysis will be carried out using data as observed. |
| The (Per-patient) Percent Improvement in the SCORAD Relative to Baseline. | 12 weeks | The (per-patient) percent improvement in the SCORAD relative to baseline, which will be analyzed using the MMRM approach described for the primary efficacy endpoint. Improvement is measured as the reduction in the score. |
| Change in IGA Score | 12 weeks | Change in Investigator Global Assessment score (IGA) at week 12 as compared to baseline for both arms of the study in subjects with atopic dermatitis. IGA is a score between 0-5, with 0 being all clear, 1 being almost clear, 2 being mild disease, 3 being moderate disease, 4 being severe disease and 5 being very severe disease. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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).
ILV-094: IV infusion of ILV-094 | 40 |
| 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).
Placebo Comparator: 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). | 20 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lack of Efficacy | 1 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo Comparator | ILV-094 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 40 Participants | 60 Participants |
| Age, Continuous | 41.3 years STANDARD_DEVIATION 16.3 | 40.5 years STANDARD_DEVIATION 14.9 | 40.5 years STANDARD_DEVIATION 15.3 |
| Region of Enrollment United States | 20 participants | 40 participants | 60 participants |
| Sex: Female, Male Female | 11 Participants | 17 Participants | 28 Participants |
| Sex: Female, Male Male | 9 Participants | 23 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 40 | 0 / 20 |
| serious Total, serious adverse events | 2 / 40 | 0 / 20 |
Outcome results
Primary
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).
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ILV-094 | Percentage Change in SCORAD | -18.8 percentage change | Standard Error 2.9 |
| Placebo Comparator | Percentage Change in SCORAD | -11.7 percentage change | Standard Error 3.9 |
Secondary
Change in IGA Score
Change in Investigator Global Assessment score (IGA) at week 12 as compared to baseline for both arms of the study in subjects with atopic dermatitis. IGA is a score between 0-5, with 0 being all clear, 1 being almost clear, 2 being mild disease, 3 being moderate disease, 4 being severe disease and 5 being very severe disease.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ILV-094 | Change in IGA Score | -0.6 score on a scale | Standard Error 0.1 |
| Placebo Comparator | Change in IGA Score | -0.3 score on a scale | Standard Error 0.1 |
Secondary
The Percentage of Patients Who Achieve an Improvement of 50% or Greater From Their Baseline Objective SCORAD at Week 12 of ILV-094 Treatment
The SCORAD50 captures individuals who achieved 50% or greater improvement from baseline SCORAD score. This outcome measure is the percentage of participants who achieved SCORAD50 at week 12. This analysis will be performed using fisher exact test. Patients who drop-out will be considered treatment failures (non-responder approach). A sensitivity analysis will be carried out using data as observed.
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ILV-094 | The Percentage of Patients Who Achieve an Improvement of 50% or Greater From Their Baseline Objective SCORAD at Week 12 of ILV-094 Treatment | 22.2 percentage of participants |
| Placebo Comparator | The Percentage of Patients Who Achieve an Improvement of 50% or Greater From Their Baseline Objective SCORAD at Week 12 of ILV-094 Treatment | 15.0 percentage of participants |
Secondary
The (Per-patient) Percent Improvement in the SCORAD Relative to Baseline.
The (per-patient) percent improvement in the SCORAD relative to baseline, which will be analyzed using the MMRM approach described for the primary efficacy endpoint. Improvement is measured as the reduction in the score.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ILV-094 | The (Per-patient) Percent Improvement in the SCORAD Relative to Baseline. | -13.8 percentage decline in SCORAD score | Standard Error 2.7 |
| Placebo Comparator | The (Per-patient) Percent Improvement in the SCORAD Relative to Baseline. | -8.0 percentage decline in SCORAD score | Standard Error 3.1 |