A Multicenter trial to Assess the Pharmacokinetics, Safety and Efficacy of Nemolizumab in Pediatric Subjects with Moderate-to-Severe Atopic Dermatitis

Phase 1

Conditions: Moderate-to-Severe Atopic Dermatitis
MedDRA version: 21.1Level: LLTClassification code 10003639Term: Atopic dermatitisSystem Organ Class: 10040785 - Skin and subcutaneous tissue disorders
Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Registration Number: EUCTR2021-000448-23-PL

Lead Sponsor: Galderma S.A.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: A

Sex: All

Target Recruitment: 105

Inclusion Criteria

1. 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.

Are the trial subjects under 18? yes
Number of subjects for this age range: 70
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age rang

Exclusion Criteria

1. 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. Cutaneous infection within 1 week before the baseline visit or any infection requiring treatment with oral or parenteral antibiotics, antivirals, antiparasitics, or antifungals within 2 weeks before the baseline visit, or any confirmed or suspected coronavirus disease (COVID-19) infection within 2 weeks before the screening or baseline visit. Subjects may be rescreened once the infection has resolved. Resolution of COVID-19 infection can be confirmed by recovery assessment methods, as described in Section 8.3.4.2.
6. Requiring rescue therapy for AD during the run-in period or expected to require rescue therapy within 2 weeks following the baseline visit.
7. 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 (eg., 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.
8. 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 subjec

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of the study is to assess the pharmacokinetics (PK) and safety and tolerability of nemolizumab administered concomitantly with topical corticosteroids (TCS) in pediatric subjects with moderate-to-severe atopic dermatitis (AD) not adequately controlled with topical treatments.;Secondary Objective: The secondary objective of the study is to assess the efficacy of nemolizumab (CD14152) and to further characterize the relationship between nemolizumab concentrations and clinical efficacy endpoints.;Primary end point(s): Pharmacokinetics (PK):<br>•Nemolizumab serum concentrations at Weeks 4, 8, 12, 16, 32, and 52<br>•Nemolizumab serum PK parameters estimated with a population PK analysis <br><br>Safety: <br>• Incidence of adverse events (AEs), including treatment-emergent AEs (TEAEs), AEs of special interests (AESIs), AEs leading to discontinuation and serious AEs (SAEs) through the study.;Timepoint(s) of evaluation of this end point: As specified within the list of endpoints

Secondary Outcome Measures

Name	Time	Method

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