Pharmacokinetics, Safety and Efficacy of Nemolizumab in Participants With Moderate-to-Severe Atopic Dermatitis

Study Overview
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Brief Summary
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The purpose of this study is to assess the pharmacokinetics (PK), efficacy, and safety of nemolizumab in pediatric participants with moderate-to-severe atopic dermatitis (AD).

Official Title
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A Multicenter, Open-Label, Single-Group Clinical Trial to Assess the Pharmacokinetics, Safety and Efficacy of Nemolizumab (CD14152) in Pediatric Subjects (Aged 2 to 11 Years) With Moderate-to-Severe Atopic Dermatitis

Conditions
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Moderate-to-Severe Atopic Dermatitis

Intervention / Treatment
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* Drug: Nemolizumab
* Drug: Nemolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic AD that has been documented for at least 6 months for participants aged 2-6 years and at least 1 year for participants aged 7-11 years before the screening visit and confirmed according to the American Academy of Dermatology Consensus Criteria at the time of the screening visit EASI score >=16 at both screening and baseline visits IGA score >=3 at both screening and baseline visits AD involvement >=10% of BSA at both screening and baseline visits Peak (maximum) PP NRS score of at least 4.0 at both screening and baseline visits Agree to apply a moisturizer throughout the study from the screening visit daily, and liberally as needed; agree to apply an authorized topical corticosteroids (TCS) from the screening visit and throughout the study as determined appropriate by the investigator Participant and caregiver willing and able to comply with all of the time commitments and procedural requirements of the clinical trial protocol Other protocol defined inclusion criteria could apply Exclusion Criteria: Body weight less than 10 kilogram (kg) 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 Participants with a current medical history of chronic bronchitis Requiring rescue therapy for AD during the run-in period or expected to require rescue therapy within 2 weeks following the baseline visit 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 (example; polymerase chain reaction [PCR]), or human immunodeficiency virus (HIV) antibody at the screening visit History of lymphoproliferative disease, hypersensitivity (including anaphylaxis) to an immunoglobulin product and intolerance to low or mid potency topical corticosteroids Known or suspected immunosuppression Participants unwilling to refrain from using prohibited medications during the clinical trial. Other protocol defined exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Participants aged 7-11 years<br>Participants aged 7-11 years will receive nemolizumab for 52 weeks. | Drug: Nemolizumab<br>* Participants will receive subcutaneous (SC) injection of 10, 20 or 30 milligrams (mg) nemolizumab, every 4 weeks (Q4W) for 52 weeks with a loading dose of 20, 40 or 60 mg at Day 1 based on the body weight.<br>* Other names: CD14152;|
| Experimental: Cohort 1.1: Participants aged 7-11 years<br>Participants aged 7-11 years will receive nemolizumab for 52 weeks. | Drug: Nemolizumab<br>* Participants will receive SC injection of 5, 10 or 15 mg nemolizumab, Q4W for 52 weeks with a loading dose of 10, 20 or 30 mg at Day 1 based on the body weight.<br>* Other names: CD14152;|
| Experimental: Cohort 2: Participants aged 2-6 years<br>Participants aged 2-6 years will receive nemolizumab for 52 weeks. | Drug: Nemolizumab<br>* Participants will receive SC injection of 5, 10 or 15 mg nemolizumab, Q4W for 52 weeks with a loading dose of 10, 20 or 30 mg at Day 1 based on the body weight.<br>* Other names: CD14152;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nemolizumab Serum Concentrations of Pediatric Participants |  | At Week 4, 8, 12, 16, 32 and 52 | 
| Apparent Total Body Clearance (Cl/F) of Nemolizumab |  | At Week 4, 8, 12, 16, 32 and 52 | 
| Apparent Volume of Distribution (Vd/F) of Nemolizumab |  | At Week 4, 8, 12, 16, 32 and 52 | 
| Absorption Rate Constant (Ka) of Nemolizumab |  | At Week 4, 8, 12, 16, 32 and 52 | 
| Maximum Observed Serum Concentration (Cmax) of Nemolizumab |  | At Week 4, 8, 12, 16, 32 and 52 | 
| Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Nemolizumab |  | At Week 4, 8, 12, 16, 32 and 52 | 
| Time to Reach the Maximum Observed Serum Concentration (Tmax) of Nemolizumab |  | At Week 4, 8, 12, 16, 32 and 52 | 
| Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Nemolizumab |  | At Week 4, 8, 12, 16, 32 and 52 | 
| Apparent Terminal Half-life (t1/2) of Nemolizumab |  | At Week 4, 8, 12, 16, 32 and 52 | 
| Number of Participants with Treatment Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs), Adverse Events Leading to Discontinuation and Serious Adverse Events (SAEs) |  | Baseline through Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Each Visit up to Week 52 | EASI assesses severity and extent of AD signs through a composite score of erythema, induration/population, excoriation, and lichenification. The severity will be assessed on a scale of 0 (absent) to 3 (severe) for each of the 4 body areas: head/neck, trunk, upper limbs, and lower limbs, with half points allowed. The EASI score can range from 0 to 72 with higher scores representing greater severity of atopic dermatitis. | Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | 
| Absolute Change From Baseline in Eczema Area and Severity Index (EASI) Score at Each Visit up to Week 52 | EASI assesses severity and extent of AD signs through a composite score of erythema, induration/population, excoriation, and lichenification. The severity will be assessed on a scale of 0 (absent) to 3 (severe) for each of the 4 body areas: head/neck, trunk, upper limbs, and lower limbs, with half points allowed. The EASI score can range from 0 to 72 with higher scores representing greater severity of atopic dermatitis. | Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | 
| Number of Participants Achieving 50%, 75% or 90% Response From Baseline in Eczema Area and Severity Index (EASI-50, EASI-75 and EASI-90) at Each Visit up to Week 52 | EASI assesses severity and extent of AD signs through a composite score of erythema, induration/population, excoriation, and lichenification. The severity will be assessed on a scale of 0 (absent) to 3 (severe) for each of the 4 body areas: head/neck, trunk, upper limbs, and lower limbs, with half points allowed. The EASI score can range from 0 to 72 with higher scores representing greater severity of atopic dermatitis. EASI-50, EASI-75 and EASI-90 responders will be the participants who achieved >=50%, >=75% and >=90% overall improvement in EASI score respectively from baseline to Week 52. | Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | 
| Investigator's Global Assessment (IGA) Success Rate at Each Visit up to Week 52 | IGA is a 5-point scale used by the investigator or trained designee to evaluate the global severity of AD. The Investigator will review the participant's skin and give a score of 0 (Clear), 1 (Almost clear), 2 (Mild), 3 (Moderate), or 4 (Severe). | Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | 
| Change From Baseline in Body Surface Area (BSA) Involvement by Atopic Dermatitis (AD) |  | Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | 
| Absolute Change From Baseline in Weekly Average of Peak Pruritus Numeric Rating Scale (PP NRS) Score at Each Visit up to Week 52 | Pruritus NRS is a scale that will be used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores are provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicate worse outcome. | Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | 
| Percent Change From Baseline in Weekly Average of Peak Pruritus Numeric Rating Scale (PP NRS) Score at Each Visit up to Week 52 | Pruritus NRS is a scale that will be used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores are provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicate worse outcome. | Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | 
| Proportion of Participants With an Improvement of >= 4 From Baseline in Weekly Average of Peak Pruritus Numeric Rating Scale (PP NRS) at Each Visit up to Week 52 | Pruritus NRS is a scale that will be used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores are provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicate worse outcome. | Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | 
| Absolute Change From Baseline in Weekly Average of Average Pruritus Numeric Rating Scale (NRS) Score at Each Visit up to Week 52 | Pruritus NRS is a scale that will be used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores are provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicate worse outcome. | Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | 
| Percent Change From Baseline in Weekly Average of Average Pruritus Numeric Rating Scale (NRS) Score at Each Visit up to Week 52 | Pruritus NRS is a scale that will be used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores are provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicate worse outcome. | Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | 
| Absolute Change From Baseline in Weekly Average of Sleep Disturbance Numeric Rating Scale (NRS) Score at Each Visit up to Week 52 | The sleep disturbance NRS is a scale used by the participants to report the degree of their sleep loss related to AD. Participants will be asked the following questions in their local language: how would you rate your sleep last night? On a scale of 0 to 10, with 0 being 'no sleep loss related to signs/symptoms of AD' and 10 being 'I cannot sleep at all due to the signs/symptoms of AD'. Higher scores indicate worse outcome. | Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | 
| Percent Change From Baseline in Weekly Average of Sleep Disturbance Numeric Rating Scale (NRS) Score at Each Visit up to Week 52 | The sleep disturbance NRS is a scale used by the participants to report the degree of their sleep loss related to AD. Participants will be asked the following questions in their local language: how would you rate your sleep last night? On a scale of 0 to 10, with 0 being 'no sleep loss related to signs/symptoms of AD' and 10 being 'I cannot sleep at all due to the signs/symptoms of AD'. Higher scores indicate worse outcome. | Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | 
| Proportion of Participants Receiving any Rescue Therapy by Rescue Treatment |  | Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | 
| Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Each Visit up to Week 52 | SCORAD is a clinical tool for assessing the severity and the extent of AD signs and symptoms. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). | Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | 
| Change From Baseline in Children's Dermatology Life Quality Index (cDLQI) For Participants >=4 Years of Age up to Week 16 and Week 52 | The DLQI is a validated 10-item questionnaire covering domains including symptoms/feelings, daily activities, leisure, work/school, personal relationships, and treatment. The participant will rate each question ranging from 0 (not at all) to 3 (very much) and score ranges from 0 to 30. A higher total score indicates a poorer quality of life (QoL). | Baseline, Week 16 and Week 52 | 
| Change From Baseline in Infants' Dermatology Life Quality Index (iDLQI) For Participants <4 Years of Age From Baseline up to Week 16 and up to Week 52 | The DLQI is a validated 10-item questionnaire covering domains including symptoms/feelings, daily activities, leisure, work/school, personal relationships, and treatment. The participant will rate each question ranging from 0 (not at all) to 3 (very much) and score ranges from 0 to 30. A higher total score indicates a poorer quality of life (QoL). | Baseline, Week 16 and Week 52 | 
| Change From Baseline in Patient-Oriented Eczema Measure (POEM) up to Week 16 and Week 52 | The POEM is a 7-item questionnaire that assessed disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life [QOL]). | Baseline, Week 16 and Week 52 | 
| Pharmacokinetic (PK)/Pharmacodynamic (PD) Relationship Between Nemolizumab Serum Concentration and Changes in Peak Pruritus Numeric Rating Scale (PP NRS) | The relationship between nemolizumab serum concentrations will be evaluated using correlation and/or linear regression methods to evaluate possible associations with changes in PP-NRS score. | Baseline, Week 16 and Week 52 | 
| Pharmacokinetic (PK)/Pharmacodynamic (PD) Relationship Between Nemolizumab Serum Concentration and Changes in Eczema Area and Severity Index (EASI) Score | The relationship between nemolizumab serum concentrations will be evaluated using correlation and/or linear regression methods to evaluate possible associations with changes in EASI score. | Baseline, Week 16 and Week 52 | 
| Pharmacokinetic (PK)/Pharmacodynamic (PD) Relationship Between Nemolizumab Serum Concentration and Changes in Investigator's Global Assessment (IGA) Score | The relationship between nemolizumab serum concentrations will be evaluated using correlation and/or linear regression methods to evaluate possible associations with changes in IGA score. | Baseline, Week 16 and Week 52 | 
| Number of Participants with Positive Anti-Drug Antibody (ADA) for Nemolizumab |  | Baseline, Week 16 and Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atopic Dermatitis, Nemolizumab, CD14152