Clinical trial NCT00119158: Combination Therapy for Atopic Dermatitis
Official title: An Exploratory Double-blind, Randomized, Vehicle-controlled, Paired Study to Evaluate the Efficacy and Safety of Concomitant Use of Elidel Cream 1% and Cutivate Cream 0.05% in Patients With Severe Lesions of Atopic Dermatitis (AD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atopic Dermatitis
Keywords: THerapy for acute moderate to severe flares
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2005-07-13
Enrollment: 90
Sex: ALL
Minimum age (years): 2
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in the m-EASI (Eczema Area Severity Index) Score.
timeFrame: up to 15 days
Secondary outcomes:
measure: The Time to Clearance of the Disease
timeFrame: assessed up to 30 days following drug application
measure: The Time to the First Day When m-EASI is Scored by the Investigator as 2 or Less
timeFrame: up to one week
measure: The Percentage of Target Areas Reaching a l-IGA (Localized Investigator Global Assessment (l-IGA) or 0 or 1)
timeFrame: up to 15 days
measure: The Percentage of Target Areas Improved (i.e., Decrease in Localized Investigator Global Assessmet (l-IGA) Score From Baseline)
timeFrame: up to 15 days
measure: The Percentage of Target Areas Reaching a m-EASI (Modifed-Eczema Area Severity Index) Score of 2 or Less
timeFrame: up to one week
measure: Change From Baseline in Patients' Self Assessment of Disease Severity (PSA) of Target Areas
timeFrame: 30 days
Other outcomes:
Locations:
city: Denver
country: United States
facility: National Jewish Research Medical Center
state: Colorado
city: Chicago
country: United States
facility: Northwestern University School of Medicine
state: Illinois
city: Houston
country: United States
facility: University of Texas at Houston Medical School
state: Texas
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Jonathan M Spergel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Spergel J, Hultsch T. Pimecrolimus cream 1% and fluticasone propionate cream 0.05% versus fluticasone propionate cream 0.05% for the treatment of flares of atopic dermatitis. 28th Annual Hawaii Dermatology Seminar, 2004
citation: Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA. New insights into atopic dermatitis. J Clin Invest. 2004 Mar;113(5):651-7. doi: 10.1172/JCI21060.
citation: Grassberger M, Baumruker T, Enz A, Hiestand P, Hultsch T, Kalthoff F, Schuler W, Schulz M, Werner FJ, Winiski A, Wolff B, Zenke G. A novel anti-inflammatory drug, SDZ ASM 981, for the treatment of skin diseases: in vitro pharmacology. Br J Dermatol. 1999 Aug;141(2):264-73. doi: 10.1046/j.1365-2133.1999.02974.x.
citation: Eichenfield LF, Lucky AW, Boguniewicz M, Langley RG, Cherill R, Marshall K. 1% pimecrolimus cream for atopic dermatitis. Arch Dermatol. 2003 Oct;139(10):1369-70; author reply 1370-1. doi: 10.1001/archderm.139.10.1369. No abstract available.
citation: Wahn U, Bos JD, Goodfield M, Caputo R, Papp K, Manjra A, Dobozy A, Paul C, Molloy S, Hultsch T, Graeber M, Cherill R, de Prost Y; Flare Reduction in Eczema with Elidel (Children) Multicenter Investigator Study Group. Efficacy and safety of pimecrolimus cream in the long-term management of atopic dermatitis in children. Pediatrics. 2002 Jul;110(1 Pt 1):e2. doi: 10.1542/peds.110.1.e2.
citation: Lee MJ, Pyszczynski N, Jusko WJ. Combined inhibition effects of tacrolimus and methylprednisolone on in vitro human lymphocyte proliferation. Immunopharmacol Immunotoxicol. 1995 May;17(2):335-45. doi: 10.3109/08923979509019755.
citation: Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M. The eczema area and severity index (EASI): assessment of reliability in atopic dermatitis. EASI Evaluator Group. Exp Dermatol. 2001 Feb;10(1):11-8. doi: 10.1034/j.1600-0625.2001.100102.x.