Alitretinoin for Hand eczema

Inclusion criteria

• {"criterion_text":"- • Age ≥ 18 years and ≤ 75 years\n- • Moderate, severe or very severe hand eczema for a minimum duration of 3 months as defined by a Physician Global Assessment (PGA) using a validated Photoguide (16), including all clinical types of hand eczema as defined by the Danish Contact Dermatitis Group\n- • Refractory to standard therapy, defined as: o 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 o Patients had also received standard skin care, including emollients and barrier protection as appropriate, without significant improvement o Patients had avoided irritants and contact allergens, if identified, without significant improvement\n- • 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\n- • Able to provide written Informed Consent\n- • Able to speak and read the Dutch language"}

Exclusion criteria

• {"criterion_text":"- General criteria prior to randomization • Treated with alitretinoin or cyclosporine in the previous 3 months • 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. For systemic prednisolone; patients with treatment within the previous 2 weeks will be excluded • 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) (17) • 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"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- 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"}

Primary endpoints

• {"endpoint_text":"- In this study the main endpoint is the between-group difference in response to treatment between baseline and 24 weeks of treatment.","definition_or_measurement_approach":"Between-group difference in response to treatment between baseline and 24 weeks of treatment. No further measurement definition for the primary endpoint is provided in the available record."}

Secondary endpoints

• {"endpoint_text":"- Between-group difference in reaching an improvement of ≥ 2 steps on the PGA score, based on a validated Photographic Guide developed by Coenraads et al (16) at 24 weeks of treatment.","definition_or_measurement_approach":"Improvement of ≥ 2 steps on the Physician Global Assessment (PGA) score using a validated Photographic Guide by Coenraads et al."}
• {"endpoint_text":"- Between-group difference in response to treatment between baseline and 12 weeks of treatment.","definition_or_measurement_approach":"Between-group difference in response at 12 weeks compared to baseline; no additional measurement details provided beyond timing."}
• {"endpoint_text":"- Between-group difference in mean change between baseline and week 4, 8, 12 and 24, assessed by the Hand Eczema Severity Index (HECSI) score.(23) The HECSI is an objective severity assessment based on clinical symptoms only. It includes erythema, fissures, vesicles, scaling, oedema, papules and measurement of the affected area. The score ranges from 0-360, with a score > 28 indicating severe hand eczema.","definition_or_measurement_approach":"Mean change in HECSI score at weeks 4, 8, 12 and 24 versus baseline. HECSI score range 0-360; >28 indicates severe hand eczema."}
• {"endpoint_text":"- Between-group difference in time to response (achieving ‘clear’/’almost clear’ in the PGA score). This is only measured at control visits so possible outcome is limited to 4, 8, 12 and 24 weeks. This will be corrected using statistical methods (see paragraph 10.2).","definition_or_measurement_approach":"Time to achieving 'clear'/'almost clear' on PGA measured at scheduled control visits (4, 8, 12, 24 weeks); statistical correction methods applied as described in protocol."}
• {"endpoint_text":"- Between-group mean change in quality of life between baseline and 12 and 24 weeks, assessed by the Quality Of Life in Hand Eczema Questionnaire (QOLHEQ). The QOLHEQ is a multi domain disease specific instrument for hand eczema assessing impairments in quality of life. The score ranges from 0-120, with 120 indicating worst quality of life.","definition_or_measurement_approach":"Mean change in QOLHEQ score at weeks 12 and 24 versus baseline. QOLHEQ range 0-120; higher worse."}
• {"endpoint_text":"- Between-group difference in patients reporting improvement as ‘clear or almost clear’ at week 12 and 24, assessed by Patient Global Assessment (PaGA). The PaGA takes signs and symptoms into account. It covers 6 degrees of improvement: ‘clear or almost clear’ (at least 90% clearing of disease signs and symptoms compared to baseline), ‘marked improvement’ (at least 75% clearing), ‘moderate improvement’ (at least 50% clearing), ‘mild improvement’ (at least 25% clearing), ‘no change’, or ‘worsening’","definition_or_measurement_approach":"Proportion of patients reporting 'clear or almost clear' on PaGA at weeks 12 and 24. PaGA categories defined with percent clearings as provided."}
• {"endpoint_text":"- Safety and tolerability • Adverse events in both groups will be registered","definition_or_measurement_approach":"Adverse events will be recorded in both treatment groups; no further safety assessment details provided in the available record."}
• {"endpoint_text":"- Between-group difference in mean Quality Adjusted Life Years (QALY’s) measured by the EQ-5D-5L score at baseline, week 12 and week 24. The EQ-5D-5L is a measure for HRQoL and utility values. The EQ-5D-5L questionnaire includes a descriptive system, which comprises 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Moreover it includes a visual analog scale (VAS),that records the respondent's self-rated health status on graduated (0–100) scale","definition_or_measurement_approach":"Mean QALYs derived from EQ-5D-5L measured at baseline, week 12 and week 24; EQ-5D-5L includes descriptive system and VAS (0-100)."}
• {"endpoint_text":"- Direct medical costs will be calculated using standardized prices for consultations, treatments (alitretinoin, cyclosporine, corticosteroids, emollients, antibiotics), diagnostic tests, lab measurements, GP visits for hand eczema, and hospital admissions (inpatient/daycare). Patients will track out-of-pocket expenses for OTC medications and other hand eczema products. Direct non-medical costs, like travel expenses, will follow average travel costs to the hospital as per Dutch healthcare guidelin","definition_or_measurement_approach":"Direct medical and non-medical costs calculated using standardized prices; patients track out-of-pocket expenses. Method follows Dutch healthcare guidelines."}
• {"endpoint_text":"- Indirect costs, consisting mainly of productivity loss, will be also be calculated using tables from the guidelines with average income of Dutch workers stratified by age and gender, corrected for shift working / irregular working hours.","definition_or_measurement_approach":"Indirect costs (productivity loss) calculated using guideline tables with average income stratified by age and gender and corrected for shift/irregular working hours."}

Netherlands

Earliest CTIS Part Ii Submission Date

04-11-2024

Latest Decision Or Authorization Date

08-11-2024

Processing Time Days

4

Number Of Sites

1

Number Of Participants

78

Primary sponsor

Full Name

Universitair Medisch Centrum Groningen

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands