Atopic Dermatitis
Conditions
Keywords
THerapy for acute moderate to severe flares
Brief summary
Atopic dermatitis is a chronic relapsing disease with acute flares. The standard therapy is to treat acute flares using topical medications. The two most common classes of topical medications for atopic dermatitis (AD) are topical corticosteroids and topical calcineurin inhibitors. Pimecrolimus and topical corticosteroids exert their activity by different mechanisms, there may be a synergistic effect of the combination therapy. Therefore, a combination therapy may provide a faster resolution of severe skin lesions and consequently reduce the duration of the topical corticosteroid treatment. Another benefit of the combination therapy maybe the use of a lower potency corticosteroid to achieve the same degree of clearance. The hypothesis of this trial is that the combination of the two agents will lead to faster clearance than the single agent of topical corticosteroids.
Detailed description
This trial is a double-blind controlled trial of fluticasone cream daily and pimecrolimus cream BID versus fluticasone cream daily and placebo cream BID for the treatment of acute flares of atopic dermatitis. While pimecrolimus cream 1% has been proven to be effective in mild and moderate Atopic dermatitis (AD), there is a need for a fast control of severe skin lesions. On the other hand, reducing the duration of the topical corticosteroid treatment is a reasonable approach to minimize the occurrence of adverse effects. Because pimecrolimus and topical corticosteroids exert their activity by different mechanisms, there may be a synergistic effect of the combination therapy. Therefore, a combination therapy may provide a faster resolution of severe skin lesions and consequently reduce the duration of the topical corticosteroid treatment. Another benefit of the combination therapy maybe the use of a lower potency corticosteroid to achieve the same degree of clearance. In vitro data have demonstrated that a combination of steroids and tacrolimus has synergistic effects on in vitro human lymphocyte proliferation. In addition, it has previously been reported, in a pilot investigation in two subjects, that a combination regimen of pimecrolimus 1% twice a day and fluticasone propionate cream 0.05% once daily was superior to fluticasone propionate cream 0.05% once daily in the acute treatment of atopic dermatitis (AD). This study is conducted to validate these findings in a larger number of patients.
Interventions
DRUGCombination of pimecrolimus and fluticasone
Pimecrolimus cream twice a day and fluticasone cream once a day
DRUGpimecrolimus
apply daily with fluticasone cream for flares
Sponsors
Novartis Pharmaceuticals
Children's Hospital of Philadelphia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Age 2 to 65 years * Clinical diagnosis of (Atopic Dermatitis) AD according to the American Academy of Dermatology (AAD) Consensus Conference (2001) * At least two lesions of AD on symmetrical part of the body (same location for each side of the body), of severe intensity (m-EASI is at least 7 on each site, with erythema of at least 3 (severe) and papulation/infiltration of at least 3 (severe)) and similar severity (m-EASI does not differ from more than 2 points on both sides) * Signed written informed consent * Willingness and ability to comply with the study requirements * Female is able to enter and participate in this study if she is of: * Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) or * Childbearing potential, has a negative pregnancy test (urine) at the screen visit and agrees to an adequate method of birth control throughout the study (which may, at the investigator's discretion, include abstinence)
Exclusion criteria
* History of immune deficiencies or history of malignant disease * Patients with moderate to severe lichenification at the target areas (i.e. score 2 or 3) * Active cutaneous bacterial, viral or fungal infections in target areas * History of other skin disorders, including Netherton syndrome, that could interfere with the evaluations * Use of any topical treatment known or suspected to have an effect on atopic dermatitis within one week prior to the screen visit (except for calcineurin inhibitors, for which the washout is 2 weeks) * Use of any systemic treatment (including phototherapy) known or suspected to have an effect on AD within four weeks prior to the screen visit \[(patients on a stable and low dose of inhaled steroids, on a stable dose of anti histamines, on stable dose of leukotriene antagonists, or receiving occasional short-acting b2-agonists for the treatment of asthma and topical corticosteroids (nasal spray) for the treatment of allergic rhinitis may participate). High-dose inhaled corticosteroids (\> 440 mcg of fluticasone a day) and anti-IgE products are not permitted\]. * Known sensitivity to pimecrolimus or vehicle (placebo) or fluticasone propionate cream or any of their ingredients * Patients with severe medical condition(s) that in the view of the investigator prohibits participation in the study * Use of any other investigational agent in the last 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the m-EASI (Eczema Area Severity Index) Score. | up to 15 days | Eczema Area severity index (EASI) is a composition of scores based on area of eczema involved, (0 = mild to 3 = severe) for four separate Atopic Dermatitis (AD) symptoms: erythema,infiltration ⁄population, excoriation and ichenification. Total score 0-12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Time to the First Day When m-EASI is Scored by the Investigator as 2 or Less | up to one week | Time to partial clearance of the localized eczema lesion assessed by the investigator is measured in days |
| The Percentage of Target Areas Reaching a l-IGA (Localized Investigator Global Assessment (l-IGA) or 0 or 1) | up to 15 days | The Investigator Global Assessment (IGA) and l-IGA were graded on a scale of 0-4 (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe). The percentage of eczema lesions from the total population that reach almost clear |
| The Time to Clearance of the Disease | assessed up to 30 days following drug application | The time to clearance of eczema measured in days |
| The Percentage of Target Areas Reaching a m-EASI (Modifed-Eczema Area Severity Index) Score of 2 or Less | up to one week | The EASI is a measure of Atopic Dermatitis (AD) severity. A m-EASI score (0-12) was also calculated as the sum of severity (0 = mild to 3 = severe) for four separate AD symptoms: erythema, infiltration ⁄population, excoriation and lichenification. The percentage of participants whose eczema reaches almost clear |
| Change From Baseline in Patients' Self Assessment of Disease Severity (PSA) of Target Areas | 30 days | The patient or caregiver assessment of eczema severity (PSA) was recorded daily in a diary using a 0-4 scale similar to that of the IGA.(0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease,4 = severe disease). Difference in value of PSA from baseline to end of study |
| The Percentage of Target Areas Improved (i.e., Decrease in Localized Investigator Global Assessmet (l-IGA) Score From Baseline) | up to 15 days | The percentage of eczema areas that show improvement in l-IGA score. The l-IGA were graded on a scale of 0-4 (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe disease). |
Countries
United States
Participant flow
Recruitment details
Medical clinics at academic centers
Pre-assignment details
Patients are self controls. Equivalent areas of eczema were compared
Participants by arm
| Arm | Count |
|---|---|
| Active Therapy Patients had equivalent eczema on each side of the body. One side of the body was treated with 1% pimecrolimus cream twice a day and fluticasone cream once a day. The opposite side of the body was treated with placebo cream twice a day and fluticasone cream once a day | 45 |
| Placebo Arm Patients had equivalent eczema on each side of the body. One side of the body was treated with 1% pimecrolimus cream twice a day and fluticasone cream once a day. The opposite side of the body was treated with placebo cream twice a day and fluticasone cream once a day | 45 |
| Total | 90 |
Baseline characteristics
| Characteristic | Placebo Arm | Active Therapy | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 22 Participants | 22 Participants | 44 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 23 Participants | 46 Participants |
| Age Continuous | 16.2 years STANDARD_DEVIATION 17.4 | 16.2 years STANDARD_DEVIATION 17.4 | 16.2 years STANDARD_DEVIATION 17.4 |
| Region of Enrollment United States | 45 participants | 45 participants | 90 participants |
| Sex: Female, Male Female | 27 Participants | 27 Participants | 54 Participants |
| Sex: Female, Male Male | 18 Participants | 18 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 45 | 0 / 45 |
| serious Total, serious adverse events | 0 / 45 | 0 / 45 |
Outcome results
Primary
Change From Baseline in the m-EASI (Eczema Area Severity Index) Score.
Eczema Area severity index (EASI) is a composition of scores based on area of eczema involved, (0 = mild to 3 = severe) for four separate Atopic Dermatitis (AD) symptoms: erythema,infiltration ⁄population, excoriation and ichenification. Total score 0-12
Time frame: up to 15 days
Population: Analysis was per protocol, last observation carried forward
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Therapy | Change From Baseline in the m-EASI (Eczema Area Severity Index) Score. | 5.04 units of a 0-12 scale | Standard Deviation 2.7 |
| Placebo Arm | Change From Baseline in the m-EASI (Eczema Area Severity Index) Score. | 4.77 units of a 0-12 scale | Standard Deviation 2.4 |
p-value: <0.05t-test, 2 sided
Secondary
Change From Baseline in Patients' Self Assessment of Disease Severity (PSA) of Target Areas
The patient or caregiver assessment of eczema severity (PSA) was recorded daily in a diary using a 0-4 scale similar to that of the IGA.(0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease,4 = severe disease). Difference in value of PSA from baseline to end of study
Time frame: 30 days
Secondary
The Percentage of Target Areas Improved (i.e., Decrease in Localized Investigator Global Assessmet (l-IGA) Score From Baseline)
The percentage of eczema areas that show improvement in l-IGA score. The l-IGA were graded on a scale of 0-4 (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe disease).
Time frame: up to 15 days
Secondary
The Percentage of Target Areas Reaching a l-IGA (Localized Investigator Global Assessment (l-IGA) or 0 or 1)
The Investigator Global Assessment (IGA) and l-IGA were graded on a scale of 0-4 (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe). The percentage of eczema lesions from the total population that reach almost clear
Time frame: up to 15 days
Secondary
The Percentage of Target Areas Reaching a m-EASI (Modifed-Eczema Area Severity Index) Score of 2 or Less
The EASI is a measure of Atopic Dermatitis (AD) severity. A m-EASI score (0-12) was also calculated as the sum of severity (0 = mild to 3 = severe) for four separate AD symptoms: erythema, infiltration ⁄population, excoriation and lichenification. The percentage of participants whose eczema reaches almost clear
Time frame: up to one week
Secondary
The Time to Clearance of the Disease
The time to clearance of eczema measured in days
Time frame: assessed up to 30 days following drug application
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Therapy | The Time to Clearance of the Disease | 9.22 days | Standard Error 4.5 |
| Placebo Arm | The Time to Clearance of the Disease | 7.88 days | Standard Error 3.88 |
Secondary
The Time to the First Day When m-EASI is Scored by the Investigator as 2 or Less
Time to partial clearance of the localized eczema lesion assessed by the investigator is measured in days
Time frame: up to one week