Alitretinoin vs Azathioprine in Severe Non-hyperkeratotic Hand Eczema

NCT ID: NCT03026907

Last Updated: 2018-05-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 116 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-31
• Study Completion Date: 2019-12-31

Brief Summary

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.

Conditions

Hand Eczema

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Alitretinoin

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

Group Type: ACTIVE_COMPARATOR

Alitretinoin

Intervention Type: DRUG

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

Azathioprine

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

Group Type: ACTIVE_COMPARATOR

Azathioprine

Intervention Type: DRUG

Oral azathioprine tablets twice daily in a dose of 1.5 or 2.5mg/kg/day, depending on the thiopurine methyltransferase (TPMT) activity.

Interventions

Alitretinoin

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

Intervention Type: DRUG

Azathioprine

Oral azathioprine tablets twice daily in a dose of 1.5 or 2.5mg/kg/day, depending on the thiopurine methyltransferase (TPMT) activity.

Intervention Type: DRUG

Other Intervention Names

Toctino; 9-cis-retinoic acid; ATC code: D11AH04; Imuran; Azafalk; ATC code: L04AX01

Eligibility Criteria

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

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Marie-Louise A Schuttelaar, MD, PhD

Principal investigator, dermatologist, MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

MLA Schuttelaar, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Locations

University Medical Center Groningen

Groningen, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

MLA Schuttelaar, MD, PhD

Role: CONTACT

m.l.a.schuttelaar@umcg.nl

+31503612520

JAF Oosterhaven, MD

Role: CONTACT

j.a.f.oosterhaven@umcg.nl

+31503610795

Facility Contacts

MLA Schuttelaar, MD, PhD

Role: primary

m.l.a.schuttelaar@umcg.nl

+31503612520

JAF Oosterhaven, MD

Role: backup

j.a.f.oosterhaven@umcg.nl

+31503610795

Other Identifiers

52232

Identifier Type: -

Identifier Source: org_study_id