Efficacy and Safety of Oral Roflumilast in Adult Patients with Chronic Hand Eczema: A Randomized Controlled Trial

The primary objective of this study is to investigate the **efficacy** and **safety** of roflumilast, a PDE4-inhibitor, in adult patients with **chronic hand eczema** (CHE). This is clinically relevant as chronic hand eczema is a persistent and often debilitating condition that can significantly impact a patient's quality of life. Evaluating the effectiveness and safety of roflumilast could provide a new therapeutic option for managing this condition.

The clinical trial focuses on evaluating the efficacy and safety of **roflumilast**, a PDE4-inhibitor, in adult patients diagnosed with **chronic hand eczema**. The study population includes both male and female participants, aged between 18 and 75 years, with a body mass index (BMI) of at least 20 kg/m². Participants are required to have a moderate to severe condition, as indicated by a Hand Eczema Severity Index (HECSI) score of 18 or higher and an Investigator's Global Assessment of Chronic Hand Eczema (IGA-CHE) score of 3 or more. The trial does not involve a vulnerable population. Participants must be able to speak, understand, and read Danish. Women of child-bearing potential are required to have a negative pregnancy test and must agree to use safe contraception throughout the study and for at least one week after the end of treatment. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed to evaluate the **efficacy** and safety of **roflumilast**, a PDE4-inhibitor, in adult patients with chronic hand eczema. This is a **randomized, controlled trial** with a double-blind design, ensuring that neither the participants nor the investigators know which treatment the participants are receiving. The trial is set to run from August 2023 to August 2028, with an estimated recruitment start date in August 2023. Participants will be randomly assigned to receive either roflumilast or a placebo, both administered orally in the form of film-coated tablets.

The trial will include several study visits, beginning with a screening visit to determine eligibility based on specific inclusion criteria, such as age between 18 and 75 years, a HECSI score of 18 or higher, and a body mass index of at least 20 kg/m². Women of childbearing potential must have a negative pregnancy test and agree to use safe contraception throughout the study and for at least one week after the end of treatment. The primary endpoint is the proportion of patients achieving at least a 75% reduction in the hand eczema severity index (HECSI75) at week 16 compared to baseline. Secondary endpoints include various measures of disease severity, quality of life, and treatment satisfaction.

Participants will be involved in the study for a maximum treatment period of 28 days for those receiving roflumilast and 16 days for those receiving the placebo. Follow-up visits will be conducted to assess the primary and secondary endpoints, as well as to monitor for any adverse events. The end-of-study visit will conclude the participant's involvement, during which final assessments will be made. Conditions that may lead to early termination from the study include the occurrence of serious adverse events or if the participant withdraws consent. The trial aims to provide valuable insights into the potential of roflumilast as a treatment for chronic hand eczema.

The clinical trial involves the administration of **Roflumilast**, a **PDE4-inhibitor**, as the experimental medication. Roflumilast is provided in the form of a film-coated tablet, with each tablet containing the active substance roflumilast. The dosage is set at a maximum daily dose of 500 micrograms, administered orally. The treatment period for Roflumilast is up to 28 days. Participants are required to adhere to the dosing schedule, and compliance will be monitored throughout the trial to ensure accurate assessment of the drug's efficacy and safety in treating chronic hand eczema.

In addition to the experimental treatment, a **placebo** is used as a comparator in this randomized controlled trial. The placebo is also presented as a film-coated tablet, identical in appearance to the Roflumilast tablet, but without the active substance. The placebo is administered orally with a maximum daily dose of 500 micrograms, and the treatment period is limited to 16 days. The use of a placebo allows for the evaluation of the true therapeutic effect of Roflumilast by providing a control for psychological and physiological responses unrelated to the active medication. Participant compliance with the placebo regimen will be similarly monitored to maintain the integrity of the trial results.

The efficacy of the clinical trial investigating the treatment of chronic hand eczema with oral **roflumilast** will be assessed using both primary and secondary endpoints. The primary endpoint is the proportion of patients achieving at least a 75% reduction in the Hand Eczema Severity Index (HECSI75) at week 16 compared to baseline. HECSI is a measure of hand eczema disease severity, with scores reflecting the extent and intensity of the disease.

Secondary endpoints include the proportion of patients achieving at least 50%, 90%, and 100% reduction in baseline HECSI at various assessments. Additional secondary measures involve changes in the Physician Global Assessment for Chronic Hand Eczema (IGA-CHE), Quality of Life Hand Eczema Questionnaire (QOLHEQ), Dermatology Life Quality Index (DLQI), and Patient's Global Assessment (PaGA). These assessments will be conducted using validated scales and questionnaires, such as the QOLHEQ and DLQI, which evaluate health-related quality of life and the impact of skin disease, respectively.

Further secondary endpoints include changes in the Numeric Rating Scale (NRS) for peak skin pain, itch, sleeplessness, and patient treatment satisfaction, as well as changes in work productivity and activity impairment due to chronic hand eczema (WPAI:CHE). Adverse events, serious adverse events, serious adverse reactions, and suspected unexpected serious adverse reactions will also be documented at assessments. The trial is designed to provide comprehensive data on the efficacy and safety of roflumilast in treating chronic hand eczema.