A phase IV randomised, double-blind, parallel-design, controlled multi-center trial of a NOVel moisturiser for Atopic dermatitis: effect on relapse prevention in children, NOVA II

The primary objective of this study is to demonstrate the **superiority** of a newly developed moisturizer in preventing eczema relapse in children with **atopic dermatitis** (AD) compared to a reference cream. This is clinically relevant as effective prevention of eczema relapse can significantly improve the quality of life for pediatric patients and reduce the burden of disease management.

Secondary objectives include:

• To study the disease severity during different stages of AD (i.e., cleared eczema vs. relapse), as evaluated by investigators, participants, and participants' parent(s) and/or legal guardian(s).
• To investigate the quality of life during different stages of AD.
• To assess participant/parent satisfaction.
• To assess the cosmetic/organoleptic properties of the investigational products.
• To investigate the number of participants with FLG loss-of-function mutations and explore if there is any evidence of a relationship to treatment effects.
• To explore the microbiome in different stages of AD (cleared vs. relapsed AD) and how the investigational product and reference product affect skin microflora over time.
• To assess tolerability and safety of the investigational products.

The clinical trial focuses on a pediatric population diagnosed with **atopic dermatitis** (eczema), specifically targeting children aged over 2 to 12 years, inclusive of both male and female participants. The study aims to evaluate the efficacy of a newly developed moisturizer in preventing eczema relapse compared to a reference cream. Participants were selected based on a confirmed diagnosis of atopic dermatitis according to the UK Working Party criteria from 1994, with additional requirements such as a history of flexural involvement, personal history of other atopic diseases, and visible mild to moderate eczema as per the objective SCORAD. The trial includes children who have experienced at least two relapses in the past year, including one at the screening visit. Participants are required to abstain from using any other prescription, over-the-counter, or natural remedies for eczema or dry skin during the study. The trial involves a vulnerable population, and informed consent was obtained from legally acceptable representatives, with assent from the participants as age-appropriate. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is a **randomized**, **double-blind**, parallel-design, controlled multi-center study aimed at evaluating the efficacy of a novel moisturizer in preventing relapse in children with **atopic dermatitis**. The trial is designed to compare the new moisturizer against a reference cream, with the primary objective being to demonstrate the superiority of the new product in preventing eczema relapse. The trial is expected to last approximately 12 months, with participant involvement spanning up to 6 months, depending on individual treatment response and relapse occurrence.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific criteria, such as age, diagnosis of atopic dermatitis, and history of eczema relapses. Following successful screening, participants will be randomized to receive either the test moisturizer or the reference cream. The study includes multiple follow-up visits to monitor treatment efficacy and safety, assess disease severity, and evaluate quality of life. These visits will occur at regular intervals throughout the study duration, with assessments including the use of tools such as PO-SCORAD and POEM.

The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted, and any remaining study-related queries will be addressed. Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with study protocols, or if the investigator deems it necessary for their safety. The trial's primary endpoint is the relapse of atopic eczema, measured as a hazard ratio, with secondary endpoints including time to relapse, proportion of participants remaining eczema-free, and quality of life assessments.

The clinical trial involves the use of several topical **creams** as part of the treatment regimen. The experimental medication, **Miniderm Duo 20 mg/g + 200 mg/g kräm**, is a cream containing the active substances **glycerol** and **urea**. It is administered topically with a maximum daily dose of 18 ml and a total maximum dose of 3240 ml over a treatment period of up to 6 weeks. The cream is provided in identical plastic pump jars of 500 ml to ensure blinding in the study.

**Essex, creme** is another treatment used in the trial, containing **paraffin white soft** and **liquid paraffin** as active substances. This cream is also applied topically, with a maximum daily dose of 18 ml and a total maximum dose of 3240 ml over a 6-week period. It serves as a comparator in the study.

**Advantan® 0.1% Creme** contains **methylprednisolone aceponate** as its active ingredient. This cream is applied topically with a maximum daily dose of 1 ml and a total maximum dose of 21 ml over a 3-week period. It is used as a standard-of-care therapy in the trial.

**Linola Fett** is a cream containing **unsaturated fatty acids (C18:2)**. It is administered topically with a maximum daily dose of 4 ml and a total maximum dose of 112 ml over a 4-week period. This cream is used as an auxiliary treatment in the study.

**ECURAL® Fettcreme, 1 mg/g Creme** contains **mometasone furoate** as its active substance. It is applied topically with a maximum daily dose of 1 ml and a total maximum dose of 21 ml over a 3-week period. This cream is also used as a standard-of-care therapy in the trial.

All treatments are administered topically, and participant compliance is monitored throughout the study to ensure adherence to the dosing schedules. The trial aims to evaluate the efficacy of the experimental moisturizer in preventing eczema relapse in children with atopic dermatitis compared to the reference creams.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints designed to evaluate the effectiveness of a novel moisturizer in preventing eczema relapse in children with **Atopic Dermatitis**. The primary endpoint is the relapse of atopic eczema, which will be measured as a hazard ratio. A relapse is defined as an episode that necessitates escalation of treatment from the perspective of the participant or their legal guardians. The date of relapse will be recorded in an eDiary and confirmed by the investigator.

Secondary endpoints include the time to relapse of atopic eczema, measured in days, and the proportion of participants remaining eczema-free after 1 to 6 months of maintenance treatment. Additional assessments will involve absolute and relative risk reduction, disease severity using PO-SCORAD and POEM at visits 1 through 4, and peak itch intensity by VAS obtained from PO-SCORAD. Weekly assessments of disease severity will be conducted using RECAP during the maintenance phase.

Quality of life will be evaluated using disease-specific instruments such as IDQoL for participants below four years and CDLQI for those above four years, as well as the general instrument EQ-5D-Y for participants above four years, all assessed at visits 1 through 4. Cream consumption will be monitored based on the weight of the investigational product before and after use at visits 2 and 4. A questionnaire will be used to evaluate the cosmetic and organoleptic properties of the creams, and another will be connected to microbiome analysis for consenting participants.

Additional assessments include the number of participants with FLG loss-of-function mutations and their relationship to treatment effects, tolerability measured as smarting or stinging on a VAS immediately and 5 minutes after the first application and after one week of treatment, and the number of participants with treatment-emergent adverse events from baseline up to day 180 or relapse.