INTEGUMENT-INFANT Phase 2 Trial Will Assess Roflumilast in Pediatric Patients with AD

Image Credit: © Olekond - stock.adobe.com

At the 2025 Revolutionizing Atopic Dermatitis (RAD) conference in Nashville, Tennessee, Arcutis Biotherapeutics presented a poster on the upcoming INTEGUMENT-INFANT trial.¹ This phase 2 study will evaluate the safety and efficacy of roflumilast (Zoryve) in infant patients between the ages of 3 months to less than 2 years with atopic dermatitis (AD).

Background

AD is most commonly diagnosed in children before 5 years of age, with the greatest incidence occurring in infants aged 3 to 6 months. Standard treatments such as corticosteroids, calcineurin inhibitors, and crisaborole, a phosphodiesterase-4 (PDE4) inhibitor, may have limited efficacy and poor tolerance in infants. Some are not approved for long-term use and may cause adverse reactions in this patient population.

The study will evaluate roflumilast, a selective PDE4 inhibitor that does not contain potentially irritating ethanol ingredients, including ethanol, propylene glycol, formaldehyde, or fragrances. The drug is available in 2 formulations: a water-based cream and a foam. The cream 0.15% version is currently approved for once-daily treatment in adult and pediatric patients aged ≥6 years with mild to moderate disease.

Roflumilast’s safety and efficacy for patients between the ages of 2 to 5 has been evaluated in the phase 3 INTEGUMENT-PED trial, a randomized, vehicle-controlled study that occurred over 4 weeks.² The upcoming phase 2, open-label, single-arm INTEGUMENT-INFANT study will assess roflumilast cream 0.05%’s tolerability, safety, and efficacy in patients aged ≥3 months to <2 years.

“Patients aged <6 years (including infants and toddlers) have higher BSA to body mass ratios and often have greater BSA involvement than patients aged ≥6 years (for whom cream 0.15% is approved); therefore, roflumilast cream 0.05% was evaluated in the INTEGUMENT-PED trial and this study,” the authors wrote. “This is expected to result in consistent pharmacokinetic, efficacy, and safety profiles in patients aged ≥3 months to <2 years and those aged 2–5 years or ≥6 years.”

Methods

Roflumilast cream 0.05% will be applied once daily for 4 weeks, similar to the INTEGUMENT-PED trial. This will include all areas, including the scalp, regardless of the number of lesions or degree of clearness. At least 4 clinic visits will be held, which include screening, baseline testing, week 2, and week 4 results.

The primary endpoints will include safety and application-site tolerability, assessing changes in vital signs, adverse effects, and serious adverse events. The exploratory endpoints will evaluate effectiveness using the total BSA and Validated Investigator Global Assessment for AD (vIGA-AD) scores, along with the specific levels on the scalp. Clinician-assessed Eczema Area and Severity Index scores (EASI) will be measured along with patient-reported outcomes, including Worst Scratch/Itch-Numeric Rating Scale (WSI-NRS), Dynamic Pruritus Score (DPS), Infants’ Dermatitis Quality of Life Index (IDQOL), Dermatitis Family Impact Questionnaire (DFI), and Patient-Oriented Eczema Measure (POEM) scores. The study participant survey will be completed by the parents and caregivers of each patient.

Patients

The patient population will include approximately 100 healthy male and female infants and toddlers at 25 clinic sites in the United States, Canada, and the Dominican Republic. Eligible participants will have a clinical diagnosis of mild to moderate AD for 1 month prior to or at the initial screening. They will also have a body surface area (BSA) involvement of ≥3% and a vIGA-AD score of mild or moderate, which includes the scalp and non-scalp areas. Scalp involvement is not required for this trial.

Patients will be required to complete a washout period if previous therapies have been used. Those with other dermatological conditions, history of major surgery, active infections, or unstable AD with a consistent requirement for high-potency corticosteroids will not be included. Additionally, pediatric patients currently experiencing food challenges or undergoing allergy testing are ineligible, as this may be associated with AD diagnosis.

Conclusion

The researchers hope that the results of the INTEGUMENT-INFANT study will support the potential use of roflumilast cream 0.05% in this patient population. Additionally, it will be the first trial to evaluate the treatment of AD on the scalp with roflumilast cream.

References

1. Hebert A, Eichenfield L, Gonzalez M, et al. INTEGUMENT-INFANT: A Phase 2, 4-Week, Open-Label Safety Study of Roflumilast Cream 0.05% in Infants Aged 3 Months to Less Than 2 Years with Atopic Dermatitis. Poster presented at the 2025 Revolutionizing Atopic Dermatitis (RAD) conference; June 6-7, 2025; Nashville, Tennessee.

2. Eichenfield L, Serrao R, Prajapati V, et al. Efficacy and safety of once-daily roflumilast cream 0.05% in pediatric patients aged 2–5 years with mild-to-moderate atopic dermatitis (INTEGUMENT-PED): A phase 3 randomized controlled trial. Pediatric Dermatology. 2025. doi:10.1111/pde.15840