AliCsa; Efficacy of oral alitretinoin versus oral cyclosporine in patients with moderate to very severe hand eczema. A randomized prospective open-label trial with blinded outcome assessment

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Medisch Centrum Groningen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Decision date (initial)

2024-11-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

University Medical Center Groningen, Department of Dermatology

External identifiers

EU CT number

2024-515140-23-00

EudraCT number

2015-003488-12

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Dose response, Therapy, Efficacy, Pharmacoeconomic

To compare the efficacy of alitretinoin and cyclosporine in patients with moderate to very severe hand eczema.

Secondary objectives 5

1. • to compare time to response
2. • to compare health related quality of life
3. • to compare improvement in severity of hand eczema, assessed by the patient
4. • to compare safety
5. • to compare cost-utility and cost-effectiveness

Conditions and MedDRA coding

Hand eczema

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. • Age ≥ 18 years and ≤ 75 years
2. • 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
3. • 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
4. • 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
5. Able to provide written Informed Consent
6. Able to speak and read the Dutch language

Exclusion criteria 4

1. 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
2. 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)
3. 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)
4. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. In this study the main endpoint is the between-group difference in response to treatment between baseline and 24 weeks of treatment.

Secondary endpoints 10

1. 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.
2. Between-group difference in response to treatment between baseline and 12 weeks of treatment.
3. 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.
4. 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).
5. 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.
6. 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’
7. Safety and tolerability • Adverse events in both groups will be registered
8. 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
9. 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
10. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Medisch Centrum Groningen

Sponsor organisation

Universitair Medisch Centrum Groningen

Address

Hanzeplein 1

City

Groningen

Postcode

9713 GZ

Country

Netherlands

Scientific contact point

Organisation

Universitair Medisch Centrum Groningen

Contact name

Marie-Louise Schuttelaar

Public contact point

Organisation

Universitair Medisch Centrum Groningen

Contact name

Marie-Louise Schuttelaar

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications