ALICsA: Alitretinoin vs Cyclosporine in Severe Recurrent Vesicular Hand Eczema

Sponsor

University Medical Center Groningen (Other)

Overall Status

Unknown status

CT.gov ID

NCT03026946

Collaborator

ZonMw: The Netherlands Organisation for Health Research and Development (Other)

Enrollment

Location

Arms

61.1

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the efficacy of alitretinoin and cyclosporine in the treatment of patients with severe recurrent vesicular hand eczema.

Condition or Disease	Intervention/Treatment	Phase
Hand Eczema	Drug: Alitretinoin Drug: cyclosporin A	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

76 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Efficacy of Oral Alitretinoin Versus Oral Cyclosporine in Patients With Severe Recurrent Vesicular Hand Eczema. A Randomized Prospective Open-label Trial With Blinded Outcome Assessment

Actual Study Start Date :

May 29, 2017

Anticipated Primary Completion Date :

Jul 1, 2022

Anticipated Study Completion Date :

Jul 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Alitretinoin Patients with severe recurrent vesicular hand eczema, randomized to treatment with alitretinoin.	Drug: Alitretinoin Oral alitretinoin capsule of 30mg once daily for a total of 24 weeks. Other Names: Toctino 9-cis-retinoic acid ATC code: D11AH04
Active Comparator: Cyclosporin A Patients with severe recurrent vesicular hand eczema, randomized to treatment with cyclosporin A.	Drug: cyclosporin A Oral cyclosporine A start dose 5 mg/kg/day (split in 2 doses), decreasing the dose after 8 weeks to 3 - 3.5 mg/kg/day (split in 2 doses). The treatment period is 24 weeks. Other Names: Neoral

Arm

Intervention/Treatment

Active Comparator: Alitretinoin

Patients with severe recurrent vesicular hand eczema, randomized to treatment with alitretinoin.

Drug: Alitretinoin

Oral alitretinoin capsule of 30mg once daily for a total of 24 weeks.

Other Names:

Toctino

9-cis-retinoic acid

ATC code: D11AH04

Active Comparator: Cyclosporin A

Patients with severe recurrent vesicular hand eczema, randomized to treatment with cyclosporin A.

Drug: cyclosporin A

Oral cyclosporine A start dose 5 mg/kg/day (split in 2 doses), decreasing the dose after 8 weeks to 3 - 3.5 mg/kg/day (split in 2 doses). The treatment period is 24 weeks.

Other Names:

Neoral

Outcome Measures

Primary Outcome Measures

Response to treatment/hand eczema severity (Photoguide) [24 weeks (end of treatment)]

Secondary Outcome Measures

Response to treatment/hand eczema severity (Photoguide) [12 weeks]
Response to treatment/hand eczema severity (Hand Eczema Severity Index, HECSI) [Week 4, 8, 12, 24]
Time to response [Week 4, 8, 12, 24]
Patient reported improvement (Patient Global Assessment, PaGA) [Week 12 and 24]
Safety and tolerability (adverse events) [Up to 24 weeks]
Cost-utility. QALY's: registered direct/indirect costs, combined with EQ-5D outcome [Week 12 and 24]
Cost-effectiveness: registered direct/indirect costs combined with the primary and secondary effectiveness outcomes (Photoguide/HECSI) [Week 12 and 24]
Quality of Life: questionnaire. [Week 12 and 24]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years and ≤ 75 years

Severe or very severe recurrent vesicular hand eczema for a minimum duration of 3 months as defined by a Physician Global Assessment (PGA) using a validated Photoguide
Refractory to standard therapy, defined as:

Patients received treatment with topical corticosteroids of class II or higher for at least 8 weeks within 3 months before enrolment, with either no response or a transient response. Patients had also received standard skin care, including emollients and barrier protection as appropriate, without significant improvement. Patients had avoided irritants and contact allergens, if identified, without significant improvement.

Women of childbearing potential are required to use at least two forms of contraception for at least 1 month before starting treatment, during treatment, and for at least 1 month after finishing treatment; these women are required to take monthly pregnancy tests
Able to provide written Informed Consent
Able to speak and read the Dutch language

Exclusion Criteria:

General criteria prior to randomization

Treated with alitretinoin or cyclosporine in the previous 3 months
Other morphologic types of hand eczema as defined by the Danish Contact Dermatitis Group
Patients with predominantly atopic dermatitis, in which the hands are also involved. (Patients with controlled atopic dermatitis, in which the hands are mainly affected, are eligible for inclusion.)
Psoriasis of the hands
Active bacterial, fungal, or viral infection of the hands
Pregnant/lactating or planning to become pregnant during the study period
Treatment with systemic medication or UV radiation within the previous 4 weeks
Mentally incompetent
Immunocompromised status
Uncontrolled arterial hypertension (minimally 3 measurements). Systolic pressure > 160 mmHg or diastolic pressure > 95 mmHg, despite starting anti-hypertensive medication (first choice amlodipine 5 mg/day)
Known or suspected allergy to ingredients in the study medications
Inclusion in a study of an investigational drug within 60 days prior to start of treatment
Current malignancy (other than successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and⁄or localized carcinoma in situ of the cervix)
Current active pancreatitis
Evidence of alcohol abuse or drug addiction
Malabsorption
Currently active gout
Recurring convulsions / epilepsy
Living vaccine (including bacillus Calmette-Guérin (BCG), varicella, measles, mumps, rubella, yellow fever, oral polio and oral typhoid) in the last 2 weeks or the planned application of such a vaccine during the study period
Chronic or recurrent infectious diseases
Contact sensitizations with clinical relevance to the hands, in which exposure to allergens is not avoided.
Hypervitaminosis A due to the use of vitamin A supplements containing >2000 IU
Use of drugs with potential to change the effective dosis of study drugs within the previous 2 weeks Laboratory exclusion criteria post randomization
Alanine aminotransferase (ALAT) and ⁄or aspartate aminotransferase (ASAT) values > 200% of the upper limit of normal
Impaired renal function as indicated by a clinically relevant abnormal creatinine value (to be determined by investigator or treating physician)
Anemia as indicated by a clinically relevant lowered hemoglobin value (to be determined by investigator or treating physician) Alitretinoin specific
Triglycerides > 200% of the upper limit of normal,
Cholesterol or low density lipoprotein (LDL) cholesterol values > 200% of the upper limit of normal
Uncontrolled hypothyroidism (to be determined by investigator or treating physician)

Cyclosporine specific:

Impaired renal function as indicated by a clinically relevant abnormal creatinine value (to be determined by investigator or treating physician)
Uremia
Hyperkalemia
Hyperuricemia in patients with a medical history of gout