Pharmacokinetics, Safety, and Efficacy of Nemolizumab with Topical Corticosteroids in Pediatric Patients with Moderate-to-Severe Atopic Dermatitis

Trial ID: 2024-514405-65-00
Protocol: RD.06.SPR.118126
Sponsor: Galderma S.A.

Trial statistics

science

test molecule

location_city

research sites

public

countries

medical_information

disease

person_search

investigators

handshake

vendors

Diseases & Conditions

Dermatitis atopic

Objectives

The primary objective of this study is to evaluate the **pharmacokinetics** (PK), safety, and tolerability of **nemolizumab** when administered concomitantly with topical corticosteroids in pediatric subjects aged 2 to 11 years with moderate-to-severe **atopic dermatitis** that is not adequately controlled with topical treatments. This is clinically relevant as it aims to determine the appropriate dosing and safety profile of nemolizumab in a pediatric population, which is crucial for managing atopic dermatitis effectively in children who do not respond well to standard topical therapies.

The secondary objective is to assess the efficacy of nemolizumab and to further characterize the relationship between nemolizumab concentrations and clinical efficacy endpoints. This will provide additional insights into the therapeutic potential and optimal dosing strategies of nemolizumab in achieving clinical improvement in atopic dermatitis.

Participants

The clinical trial involves a total of **11 participants** diagnosed with **atopic dermatitis**. The study population includes both male and female pediatric subjects, specifically those aged **2 to 11 years**. Participants are required to have moderate-to-severe atopic dermatitis that is not adequately controlled with topical treatments. The trial population was selected based on specific inclusion criteria, including a documented history of chronic atopic dermatitis for at least 6 months for those aged 2-6 years and at least 1 year for those aged 7-11 years. Additionally, participants must have an Eczema Area and Severity Index (EASI) score of 16 or higher and an Investigator's Global Assessment (IGA) score of 3 or higher. The study also considers lifestyle factors, requiring participants to apply a moisturizer daily and use authorized topical corticosteroids as needed. The trial includes both genders and considers the population as vulnerable due to the pediatric age group involved.

Plans and Procedures

The clinical trial is designed to evaluate the **pharmacokinetics**, safety, and efficacy of **nemolizumab** in pediatric subjects aged 2 to 11 years with moderate-to-severe **atopic dermatitis**. This is a multicenter, open-label, single-group study. The trial will involve the administration of nemolizumab in conjunction with topical corticosteroids. The study is expected to run from December 16, 2021, to April 30, 2025, with the primary objective of assessing the pharmacokinetics, safety, and tolerability of the drug in the specified population.

Participants will be involved in the study for a maximum treatment period of 60 weeks. The trial includes several key visits: an initial screening visit to confirm eligibility, followed by regular follow-up visits at Weeks 4, 8, 12, 16, 32, and 52 to monitor **serum concentrations** of nemolizumab and assess any adverse events. The end-of-study visit will occur at Week 52, where final assessments will be conducted. The primary endpoints include measuring nemolizumab serum concentrations and evaluating the incidence of adverse events throughout the study. Secondary endpoints focus on changes in the Eczema Area and Severity Index (EASI) score and the Investigator’s Global Assessment (IGA) success rate.

Participants are expected to adhere to the study protocol, including the application of moisturizers and authorized topical corticosteroids. Conditions that may lead to early termination from the study include the occurrence of serious adverse events or non-compliance with the study protocol. The trial is not categorized as low intervention and is classified as a Phase 4 clinical study. The study aims to provide valuable insights into the treatment of atopic dermatitis in a pediatric population, contributing to the understanding of nemolizumab's role in managing this condition.

Treatment

**Nemolizumab** is the experimental medication being evaluated in this clinical trial. It is formulated as a **solution for injection** and is administered via **subcutaneous use**. The active substance, **nemolizumab**, is a protein of other origin, and the product is classified as a biological medicinal product. The maximum daily dose of nemolizumab is 60 mg, with a total maximum dose of 210 mg over the course of the treatment period, which spans up to 60 days. The pharmaceutical form is specifically designed for injection, and the product is not a pediatric formulation. The sponsor product code for nemolizumab is CD14152 / CIM331, and it is developed by GALDERMA S.A.

In addition to the experimental treatment, participants in the study will receive non-experimental treatments, specifically topical corticosteroids (TCS), which are standard-of-care therapy for moderate-to-severe atopic dermatitis. The use of TCS is intended to be concomitant with nemolizumab administration to assess the pharmacokinetics, safety, and efficacy of the combined treatment regimen. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed treatment protocol.

Efficacy

The efficacy of **Nemolizumab** in pediatric subjects with moderate-to-severe atopic dermatitis will be assessed using several key endpoints. Primary efficacy endpoints include the measurement of **Nemolizumab** serum concentrations at specified timepoints: Weeks 4, 8, 12, 16, 32, and 52. Additionally, serum pharmacokinetic (PK) parameters will be estimated through a population PK analysis. The incidence of adverse events (AEs), including treatment-emergent AEs (TEAEs), AEs of special interest (AESIs), AEs leading to discontinuation, and serious AEs (SAEs) will also be monitored throughout the study.

Secondary efficacy endpoints focus on the clinical response of atopic dermatitis to **Nemolizumab** treatment. These include the absolute and percent change in the Eczema Area and Severity Index (EASI) score from baseline at each visit up to Week 16 and Week 52. The proportion of subjects achieving 50%, 75%, or 90% improvement in EASI (EASI-50, EASI-75, and EASI-90) will be evaluated at baseline and at each visit up to Week 16 and Week 52. Furthermore, the Investigator’s Global Assessment (IGA) success rate, defined as an IGA score of 0 (Clear) or 1 (Almost clear) with a ≥2-point improvement from baseline, will be assessed at each visit up to Week 16 and Week 52.

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

Subjects ≥7 to <12 years of age or ≥2 to <7 years of age at the screening visit. Note: Subjects aged 2 to 6 years can be enrolled only after the IA-1.1 and the IDMC has assessed interim safety data from Cohort 1.1 (aged 7 to 11 years) and provided recommendations to the Sponsor, who will then determine the eligibility of this age group for enrollment in the study and confirm the dose. The Sponsor will send a written communication to the sites confirming that the study is open for enrollment of Cohort 2 (aged 2 to 6 years). This cohort must not be enrolled in the study until such communication is received. 2. Chronic AD that has been documented for at least 6 months for subjects aged 2-6 years and at least 1 year for subjects aged 7-11 years before the screening visit and confirmed according to the American Academy of Dermatology Consensus Criteria (Appendix 1) at the time of the screening visit. 3. Eczema Area and Severity Index (EASI) score ≥16 at both screening and baseline visits. 4. Investigator’s Global Assessment (IGA) score ≥3 (based on the IGA scale ranging from 0 to 4, in which 3 is moderate and 4 is severe) at both screening and baseline visits. 5. AD involvement ≥10% of Body Surface Area (BSA) at both screening and baseline visits. 6. Peak (maximum) Pruritus Numeric Rating Scale (PP NRS) score of at least 4.0 at both screening and baseline visits: • Screening PP NRS score will be determined by a single PP NRS assessment (score ranging from 0 to 10) for the 24-hour period immediately preceding the screening visit. • Baseline PP NRS score will be determined based on the average of daily PP NRS scores (score ranging from 0 to 10) during the 7 days immediately preceding baseline (rounding not permitted). A minimum of 4 daily scores out of the 7 days immediately preceding baseline is required for this calculation. 7. Documented history by a physician and/or investigator (within 6 months before the screening visit) of inadequate response to existing topical medication or use of systemic therapies for control of the disease. 8. Agree to apply a moisturizer throughout the study from the screening visit daily, and liberally as needed; agree to apply an authorized TCS, with or without TCI, from the screening visit and throughout the study as determined appropriate by the investigator. 9. Any female of childbearing potential (i.e., a subject who has started menstruating) who is, in the opinion of the investigator, sexually active and at risk for pregnancy must be willing and able either to be strictly abstinent or to use an adequate and approved method of contraception throughout the study and for 12 weeks after the last study drug injection. Adequate and approved methods of contraception applicable for the subject and/or her partner are defined below: • true abstinence, when in line with the preferred and usual lifestyle of the subject (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.) • oral hormonal contraception. 10. Subject and caregiver willing and able to comply with all of the time commitments and procedural requirements of the clinical trial protocol. 11. Understand and sign an Informed Consent Form (ICF) and Assent Form before any investigational procedures being performed.

cancel

Exclusion Criteria

Body weight <10 kg. 2. Child in Care: a child who has been placed under the control or protection of an agency, organization, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation. 3. Subjects meeting one or more of the following criteria at screening or baseline: 3a. Had a documented asthma exacerbation requiring hospitalization in the preceding 12 months. 3b. Reporting asthma that has not been well controlled as defined by one or more of the following: • Daytime asthma symptoms >2 times per week during the preceding 3 months • Nighttime awakenings with asthma symptoms >2 times per month during the preceding 3 months • Asthma exacerbation requiring oral corticosteroid use >2 times per year 3c. Childhood Asthma Control Test (cACT) ≤19 (applies only for subjects with a history of asthma aged 7 to 11 years; cACT will not be performed for subjects aged 2 to 6 years). 3d. Peak expiratory flow (PEF) <80% of the predicted value (applies only for subjects aged 7 to 11 years; PEF will not be performed for subjects aged 2 to 6 years). Note: In the event that PEF is <80% of the predicted value at screening in patients without any history of asthma or in patients with history of asthma but with the cACT score >19, PEF testing can be repeated once within 48 hours. 4. Subjects with a current medical history of chronic bronchitis. 5. Requiring rescue therapy for AD during the run-in period or expected to require rescue therapy within 2 weeks following the baseline visit. 6. Positive serology results for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb), hepatitis C (HCV) antibody with positive confirmatory test for HCV (e.g., polymerase chain reaction [PCR]), or human immunodeficiency virus (HIV) antibody at the screening visit. Note: Subjects with a positive HBcAb and a negative HBsAg can be included in this clinical trial if hepatitis B surface antibody (HBsAb) is positive (considered immune after a natural infection). Subjects with negative confirmatory test for HCV can be included in this clinical study. In the event of rescreening, the serology tests results (e.g., HBV, HCV, HIV) from the first screening can be used by the investigator to assess the eligibility of rescreened subjects if those tests were performed within 6 weeks prior to the baseline visit. 7. Current active tuberculosis (TB) or latent TB infection or history of either untreated or inadequately treated latent or active TB according to the local applicable guidelines. Note: Subjects who have a documented history of completion of an appropriate TB treatment regimen for latent or active TB with no history of re-exposure to TB since their treatment was completed are eligible to participate in the study. In the event of rescreening, the TB tests result from the first screening can be used by the investigator to assess the eligibility of rescreened subjects if the test was performed within 6 weeks prior to the baseline visit.