Clinical trial NCT05682859: Treatment of Chronic Hand Eczema With Oral Roflumilast (HERO)
Official title: Treatment of Chronic Hand Eczema With Oral Roflumilast (HERO) - a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Chronic Hand Eczema
Lead sponsor: Bispebjerg Hospital
Sponsor class: OTHER
Collaborators: name: The Novo Nordic Foundation
First posted: 2023-01-12
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicentre, double-blinded, randomized, placebo-controlled, clinical trial with open-label extension
Primary purpose: TREATMENT

Brief summary: This study is a multicentre, double-blinded, randomized, placebo-controlled, clinical trial with open-label extension.

The purpose and aim of this study is to investigate the efficacy and safety of roflumilast (PDE4-inhibitor) in adult patients with chronic hand eczema (CHE).

Patients will receive 16-week treatment with either roflumilast or placebo tablets. Hereafter, both groups continue in open-label treatment for 12 weeks where both groups will receive treatment with roflumilast.

Detailed description: This study will investigate the efficacy and safety of roflumilast in adult patients with CHE and it is hypothesized that patients treated with oral roflumilast (500 microgram once daily) will experience an improvement in their moderate-to-severe CHE (measured by hand eczema severity index (HECSI)) and alter the skin microbiome. Secondly, it is hypothesized that patients treated with oral roflumilast will experience improved lung function and weight loss.

This study includes two phases:

Phase 1: 20 patients will receive 500 microgram tablet of roflumilast once daily for 16 weeks while 20 patients will receive placebo once daily for 16 weeks.

Phase 2: All 40 patients from phase 1 will receive 500 microgram tablet of roflumilast once daily for 12 weeks.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Age ≤ 75 years
* HECSI ≥ 18 (moderate to severe hand eczema)
* IGA-CHE ≥ 3
* Body mass index (BMI) ≥ 20 kg/m2
* Negative pregnancy test (only women of child-bearing potential (see section 2.8))
* Willing to use safe anticonception during entire study and at least 1 week after end of treatment (-5 times plasma half-life of Roflumilast). This only account for women child-bearing potential
* Speaks, understands, and reads danish.

Exclusion Criteria:

* Severe immunological disease, e.g. HIV, systemic lupus, and systemic sclerosis
* Diagnosis of current tuberculosis
* Current viral hepatitis
* History of heart failure (NYHA III-IV)
* History of moderate or severe liver failure (Child-Pugh B-C)
* Current or former depression with suicidal ideation
* Topical therapy (anti-inflammatory) for chronic hand eczema 14 days before randomization
* Topical therapy (anti-inflammatory) for chronic hand eczema during study
* Systemic therapy for chronic hand eczema 28 days before randomization
* Systemic therapy for chronic hand eczema during study
* Current treatment with oral dicloxacillin or macrolide
* Current treatment with topical antibiotics
* Diagnosis of contact eczema of clinical significance 3 months before randomization
* Previous treatment with apremilast (Otezla®) or roflumilast (Daxas®)
* Confirmed pregnancy
* Breast feeding
* Blood donation during study
* Allergy to roflumilast or any other PDE-4 inhibitor

Primary outcomes:
measure: Proportion of patients achieving at least 75% reduction in hand eczema severity index (HECSI75) at week 16 when compared to HECSI at baseline.
timeFrame: Through study completion, an average of 28 weeks
Secondary outcomes:
measure: Proportion of patients achieving at least 50% reduction in baseline HECSI (HECSI50) at assessments.
timeFrame: Through study completion, an average of 28 weeks
measure: Proportion of patients achieving at least 90% reduction in baseline HECSI (HECSI90) at assessments.
timeFrame: Through study completion, an average of 28 weeks
measure: Proportion of patients achieving at least 100% reduction in baseline HECSI (HECSI100) at assessments
timeFrame: Through study completion, an average of 28 weeks
measure: Percent change from baseline in HECSI score at assessments.
timeFrame: Through study completion, an average of 28 weeks
measure: Change (2 or more points) in physician global assessment for chronic hand eczema IGA-CHE) at assessments.
timeFrame: Through study completion, an average of 28 weeks
measure: Change from baseline in dermatology life quality index (DLQI) at assessments.
timeFrame: Through study completion, an average of 28 weeks
measure: Change from baseline in patient's global assessment (PaGA) at assessments.
timeFrame: Through study completion, an average of 28 weeks
measure: Change from baseline in numeric rating scale (NRS) - Peak skin pain on hands within the last 24 hours at assessments.
timeFrame: Through study completion, an average of 28 weeks
measure: Change from baseline in numeric rating scale (NRS) - Peak skin pain on hands within the last 7 days at assessments.
timeFrame: Through study completion, an average of 28 weeks
measure: Change from baseline in NRS - Peak itch on hands within the last 24 hours at assessments.
timeFrame: Through study completion, an average of 28 weeks
measure: Change from baseline in NRS - Peak itch on hands within the last 7 days at assessments.
timeFrame: Through study completion, an average of 28 weeks
measure: Change from baseline in NRS - sleeplessness within the last 24 hours at assessments.
timeFrame: Through study completion, an average of 28 weeks
measure: Change from baseline in NRS - sleeplessness within the last 7 at assessments.
timeFrame: Through study completion, an average of 28 weeks
measure: Change from baseline in NRS - Patient treatment satisfaction within the last 7 at assessments.
timeFrame: Through study completion, an average of 28 weeks
measure: Change from baseline in quality of life hand eczema questionnaire (QOLHEQ) at assessments.
timeFrame: Through study completion, an average of 28 weeks
measure: Change from baseline in work productivity and activity impairment: CHE (WPAI:CHE) at assessments.
timeFrame: Through study completion, an average of 28 weeks
measure: Adverse events (AEs), serious adverse events (SAEs), serious adverse reactions (SARs), and suspected unexpected serious adverse reactions (SUSARS) documented at assessments.
timeFrame: Through study completion, an average of 28 weeks
Other outcomes:
measure: Change in lung function between baseline and week 16
timeFrame: 16 weeks
measure: Change in lung function between baseline and week 16
timeFrame: 16 weeks
measure: Change in natural moisturizing factor (NMF) between baseline and week 16
timeFrame: 16 weeks
measure: Change in cytokine levels between baseline and week 16
timeFrame: 16 weeks
measure: Change in ceramides (lipids) between baseline and week 16
timeFrame: 16 weeks
measure: Change in skin bacterial communities between baseline and week 16
timeFrame: 16 weeks
Locations:
city: Copenhagen
country: Denmark
facility: Department of dermatology and veneorology, Bispebjerg Hospital
Study officials:
References: