Clinical trial NCT00817063: Efficacy and Safety of a Retinoid in the Treatment of Severe Chronic Hand Eczema
Official title: Efficacy and Safety of Alitretinoin in the Treatment of Severe Chronic Hand Eczema Refractory to Topical Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Eczema
Keywords: retinoid treatment
fingertip dermatitis
hyperkeratotic hand eczema
vesicular hand eczema
pompholyx
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Basilea Pharmaceutica
First posted: 2009-01-06
Enrollment: 599
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the safety and efficacy of alitretinoin in the treatment of severe chronic hand eczema that does not respond to treatment with potent topical steroids.

Detailed description: Chronic hand eczema (CHE)is a distressing disease that poses difficult problems for dermatologists. CHE leads to considerable work-absenteeism, disability and exclusion from labour market. Conventional treatments, including highly potent topical steroids, yield often unsatisfactory results. This study investigates the efficacy and safety of oral alitretinoin, a retinoid, in patients who have not responded to avoidance of causative factors, such as contact allergens and skin irritants, non-medicated skin care and highly potent topical steroids. Eligible patients are randomly assigned to receive alitretinoin or a placebo.

Eligibility criteria: Inclusion Criteria:

* all types of chronic hand eczema, lasting for at least 6 months since initial diagnosis
* rated as severe by the physician
* unresponsive to highly potent topical corticosteroids, such as clobetasol

Exclusion Criteria:

* patients whose disease is adequately controlled by standard non-medicated therapy, including potent topical steroids, skin moisturizers, and avoidance of allergens and irritants
* patients with known allergens and irritants, who have not made a reasonable effort to avoid the substances
* patients with psoriasis lesions
* active fungal, bacterial or viral infections of the hands
* female patients who are pregnant or breastfeeding
* female patients of childbearing potential who cannot use or will not commit to use two effective methods of contraception

Primary outcomes:
measure: Number of Participants Who Responded as Per Physician's Global Assessment (PGA) at Week 24
timeFrame: Week 24 (end-of-treatment)
Secondary outcomes:
measure: Percentage Change From Baseline in Modified Total Lesion Symptom Score (mTLSS) at the End-of-treatment
timeFrame: Baseline (Week 0) and Week 24 (end-of-treatment)
measure: Number of Participants Who Responded as Per Patient Global Assessment (PaGA) at End-of-treatment
timeFrame: Week 24 (end-of-treatment)
measure: Percentage Change From Baseline in Extent of Disease at End-of-treatment
timeFrame: Baseline (Week 0) and Week 24 (end-of-treatment)
measure: Response Duration for Responding Participants at the End-of-therapy
timeFrame: Up to 72 Weeks (including 24 weeks of treatment and 48 weeks of follow-up)
measure: Time to Relapse for Responding Participants at the End-of-therapy
timeFrame: Up to 72 Weeks (including 24 weeks of treatment and 48 weeks of follow-up)
measure: Time to Response for Responding Participants at End-of-therapy
timeFrame: Up to 72 Weeks (including 24 weeks of treatment and 48 weeks of follow-up)
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Treatment Period
timeFrame: Up to Week 24 (end-of-treatment)
measure: Number of Participants With Maximum Post Baseline Laboratory Values Outside the Marked Reference Range
timeFrame: Up to Week 28
measure: Number of Participants Referred or Not Referred to a Psychiatrist as Per Brief Summary Inventory (BSI) 53 Questionnaire up to 24 Weeks
timeFrame: Up to Week 24
measure: Change From Baseline in Patient Health Questionnaire (PHQ-9) Score Over 28 Weeks
timeFrame: Baseline (Week 0) and Week 4, 8, 12, 16, 20, 24, 28
measure: Number of Participants Meeting the Referral Criteria of Psychiatric Evaluation Over 28 Weeks
timeFrame: Up to 28 Weeks
measure: Change From Baseline in Hearing Handicap Inventory for the Elderly-Screening (HHIE-S) Over 24 Weeks
timeFrame: Baseline (Week 0) and Week 4, 8, 12, 16, 20, 24
measure: Change From Baseline in Dizziness Handicap Inventory (DHI) Over 24 Weeks
timeFrame: Baseline (Week 0) and Week 4, 8, 12, 16, 20, 24
measure: Number of Participants Responding to Tinnitus Ototoxicity Monitoring Interview (TOMI) Questionnaire Over 24 Weeks
timeFrame: Up to Week 24
measure: Percent Change From Baseline in Bone Mineral Density (BMD) by Dual Energy X-ray Absorptiometry (DXA) Over 72 Weeks
timeFrame: Baseline (Week 0) and Week 72
measure: Number of Participants With Adequecy of Images Assessed by X-ray Evaluation of Bones
timeFrame: Up to Week 72
measure: Number of Participants With Adverse Ophthalmological Change as Assessed by Fundus Photography - Intraocular Pressure
timeFrame: Up to Week 24
measure: Number of Participants With Adverse Audiological Change as Assessed by Puretone Audiogram at Highest Frequency
timeFrame: Up to Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama, Birmingham
state: Alabama
city: Tucson
country: United States
facility: Radiant Research Inc.
state: Arizona
city: Fort Smith
country: United States
facility: Johnson Dermatology
state: Arkansas
city: Little Rock
country: United States
facility: Dermatology Research of Arkansas
state: Arkansas
city: Rogers
country: United States
facility: Hull Dermatology
state: Arkansas
city: Encino
country: United States
facility: Shahram Jacobs, MD, Inc.
state: California
city: La Jolla
country: United States
facility: University of California, San Diego Dermatology Clinical Trials Unit
state: California
city: Los Angeles
country: United States
facility: Dermatology Research Associates
state: California
city: Marina Del Rey
country: United States
facility: Laser and Dermatology Center
state: California
city: Riverside
country: United States
facility: Integrated Research Group
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: San Diego
country: United States
facility: Therapeutics Clinical Research
state: California
city: San Ramon
country: United States
facility: East Bay Psoriasis Treatment Center
state: California
city: Stanford
country: United States
facility: Stanford University Dept of Dermatology
state: California
city: Vallejo
country: United States
facility: Solano Clinical Research, Dow Pharmaceutical Sciences
state: California
city: Longmont
country: United States
facility: Longmont Clinic, P.C.
state: Colorado
city: Wheat Ridge
country: United States
facility: Western State Clinical Research Inc.
state: Colorado
city: Washington
country: United States
facility: George Washington University - Medical Faculty Associates
state: District of Columbia
city: Orange Park
country: United States
facility: Park Avenue Dermatology, PA
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Research Center
state: Florida
city: Toccoa
country: United States
facility: Toccoa Clinic Medical Associates
state: Georgia
city: Nampa
country: United States
facility: Saltzer Medical Group
state: Idaho
city: Arlington Heights
country: United States
facility: Michael Bukhalo MD
state: Illinois
city: Belleville
country: United States
facility: Dermassociates, Ltd
state: Illinois
city: Schaumburg
country: United States
facility: Schaumburg Dermatology
state: Illinois
city: West Dundee
country: United States
facility: Dundee Dermatology
state: Illinois
city: Evansville
country: United States
facility: Deaconess Clinic, Inc.
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Dermatology
state: Indiana
city: New Albany
country: United States
facility: The Dermatology Center
state: Indiana
city: Plainfield
country: United States
facility: Dermatology Center of Indiana/Indiana Clinical Trials Center
state: Indiana
city: Overland Park
country: United States
facility: Kansas City Dermatology, PA
state: Kansas
city: Shawnee Mission
country: United States
facility: American Dermatology Association
state: Kansas
city: Topeka
country: United States
facility: Kansas Medical Clinic
state: Kansas
city: Louisville
country: United States
facility: Dermatology Specialists
state: Kentucky
city: Louisville
country: United States
facility: Derm Research, PLLC
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University Health Sciences, Dermatology Dept
state: Louisiana
city: Fort Gratiot
country: United States
facility: Hamzavi Dermatology Clinic
state: Michigan
city: Grand Blanc
country: United States
facility: Silverton Skin Institute
state: Michigan
city: Warren
country: United States
facility: Grekin Skin Institute
state: Michigan
city: Edina
country: United States
facility: MAPS Applied Research Center
state: Minnesota
city: Fridley
country: United States
facility: Minnesota Clinical Studies Research Center
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University Dermatology Research
state: Missouri
city: Lincoln
country: United States
facility: South Lincoln Dermatology
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Somerset
country: United States
facility: UMDNJ - Robert Wood Johnson School of Medicine, Dermatology
state: New Jersey
city: New York
country: United States
facility: St.Luke's/Roosevelt Hospital Center
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine Clinical Dermatology
state: New York
city: Rochester
country: United States
facility: Helendale Dermatology and Medical Spa
state: New York
city: Stony Brook
country: United States
facility: Derm Research Center of New York Inc.
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina, Dermatology Department
state: North Carolina
city: Wilmington
country: United States
facility: Azalea Research Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forrest University School of Medicine
state: North Carolina
city: Cincinnati
country: United States
facility: Bernstein Clinical Research Center
state: Ohio
city: Portland
country: United States
facility: Oregon Dermatology and Research Center
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Paddington Testing Co.Inc
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Kingsport
country: United States
facility: Dermatology Associates of Kingsport
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Clinical Research Center
state: Tennessee
city: Arlington
country: United States
facility: Academy of Clinical Research
state: Texas
city: Dallas
country: United States
facility: Modern Research Associates
state: Texas
city: Houston
country: United States
facility: Center for Clinical Studies
state: Texas
city: San Antonio
country: United States
facility: Dermatology Clinical Research Center of San Antonio
state: Texas
city: Webster
country: United States
facility: Center for Clinical Studies
state: Texas
city: Burlington
country: United States
facility: Fletcher Allen Health Care
state: Vermont
city: Norfolk
country: United States
facility: Virginia Clinical Research Inc.
state: Virginia
city: Bellingham
country: United States
facility: Dermatology and Laser Center NW
state: Washington
city: Seattle
country: United States
facility: Premier Clinical Research
state: Washington
city: Madison
country: United States
facility: Madison Skin & Research Inc.
state: Wisconsin
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Diepgen TL, Agner T, Aberer W, Berth-Jones J, Cambazard F, Elsner P, McFadden J, Coenraads PJ. Management of chronic hand eczema. Contact Dermatitis. 2007 Oct;57(4):203-10. doi: 10.1111/j.1600-0536.2007.01179.x.
citation: Ruzicka T, Larsen FG, Galewicz D, Horvath A, Coenraads PJ, Thestrup-Pedersen K, Ortonne JP, Zouboulis CC, Harsch M, Brown TC, Zultak M. Oral alitretinoin (9-cis-retinoic acid) therapy for chronic hand dermatitis in patients refractory to standard therapy: results of a randomized, double-blind, placebo-controlled, multicenter trial. Arch Dermatol. 2004 Dec;140(12):1453-9. doi: 10.1001/archderm.140.12.1453.
citation: Ruzicka T, Lynde CW, Jemec GB, Diepgen T, Berth-Jones J, Coenraads PJ, Kaszuba A, Bissonnette R, Varjonen E, Hollo P, Cambazard F, Lahfa M, Elsner P, Nyberg F, Svensson A, Brown TC, Harsch M, Maares J. Efficacy and safety of oral alitretinoin (9-cis retinoic acid) in patients with severe chronic hand eczema refractory to topical corticosteroids: results of a randomized, double-blind, placebo-controlled, multicentre trial. Br J Dermatol. 2008 Apr;158(4):808-17. doi: 10.1111/j.1365-2133.2008.08487.x. Epub 2008 Feb 21.
citation: Fowler JF, Graff O, Hamedani AG. A phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of alitretinoin (BAL4079) in the treatment of severe chronic hand eczema refractory to potent topical corticosteroid therapy. J Drugs Dermatol. 2014 Oct;13(10):1198-204.