Alitretinoin vs Azathioprine in Severe Non-hyperkeratotic Hand Eczema (ALIAZ)

University Medical Center Groningen (UMCG)

Status and phase: Unknown; Phase 3

Conditions: Hand Eczema

Treatments: Drug: Azathioprine; Drug: Alitretinoin

Study type: Interventional

Funder types: Other

Identifiers

NCT03026907

52232

Details and patient eligibility

About

The purpose of this study is to compare the efficacy of alitretinoin and azathioprine in the treatment of patients with severe chronic non-hyperkeratotic hand eczema.

Enrollment: 116 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age ≥ 18 years and ≤ 75 years
• Severe or very severe chronic non-hyperkeratotic 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 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

• Treatment with alitretinoin or azathioprine in the previous 3 months
• Hyperkeratotic palmar eczema as defined by the Danish Contact Dermatitis Group
• Patients with predominantly atopic dermatitis, in which the hands are also involved. Patients with mild atopic dermatitis, in which the hands are mainly affected are eligible for inclusion.
• Psoriasis
• 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
• 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
• 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
• Evidence of alcohol abuse or drug addiction
• 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)

Azathioprine specific

• Patients with low or absent thiopurine methyltransferase (TPMT) activity (defined in our center as <52 nmol/gHb/hour, combined with genotyping showing homozygous of compound heterozygous mutations) and a subsequent risk for life-threatening myelotoxicity

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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116 participants in 2 patient groups

Alitretinoin

Active Comparator group

Description:

Patients with severe chronic non-hyperkeratotic hand eczema, randomized to treatment with alitretinoin.

Treatment:

Drug: Alitretinoin

Azathioprine

Active Comparator group

Description:

Patients with severe chronic non-hyperkeratotic hand eczema, randomized to treatment with azathioprine.

Treatment:

Drug: Azathioprine