A Pharmacokinetics and Safety Study of Nemolizumab in Adolescent Participants With Atopic Dermatitis (AD)

Study Overview
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Brief Summary
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The purpose of this study was to evaluate the pharmacokinetics and safety of nemolizumab in adolescent participants with AD.

Official Title
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A Multicenter, Open-Label, Single-Group Clinical Trial to Assess the Pharmacokinetics and Safety of Nemolizumab (CD14152) in Adolescent Subjects (12-17 Years) With Moderate-to-Severe Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Biological: Nemolizumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria Male or female participants ≥ 12 to < 17 years of age Chronic AD that has been documented for at least 2 years Eczema Area and Severity Index (EASI) score ≥ 16 Investigator's Global Assessment (IGA) score ≥ 3 AD involvement ≥ 10% of Body Surface Area (BSA) Documented recent history of inadequate response to topical medications Women of childbearing potential must agree to be strictly abstinent or to use an effective and approved method of contraception throughout the study and for 12 weeks after the last study drug injection. Key Exclusion Criteria Body weight < 30 kilogram (kg) Cutaneous infection within 1 week or any infection requiring treatment with oral or parenteral antibiotics, antivirals, antiparasitics, or antifungals within 1 week History of hypersensitivity (including anaphylaxis) to an immunoglobulin product (plasma-derived or recombinant, example., monoclonal antibody) Any medical or psychological condition, or any clinically relevant laboratory abnormalities that may have put the subject at significant risk according to the investigator's judgment

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nemolizumab<br>Nemolizumab | Biological: Nemolizumab<br>* Participants received subcutaneous (SC) injection of 30 milligram (mg) of Nemolizumab every 4 weeks (Q4W) over a 16-week treatment period, with a loading dose of 60 mg on Day 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nemolizumab Serum Concentrations at Week 1-2 | Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA). | At week 1-2 | 
| Nemolizumab Serum Concentrations at Week 4 | Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA). | At week 4 | 
| Nemolizumab Serum Concentrations at Week 8 | Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA). | At week 8 | 
| Nemolizumab Serum Concentrations at Week 12 | Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA). | At week 12 | 
| Nemolizumab Serum Concentrations at Week 16 | Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA). | At week 16 | 
| Nemolizumab Serum Concentrations at Week 24 | Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA). | At week 24 | 
| Apparent Clearance After Extravascular Administration (Cl/F) of Nemolizumab | CL/F is apparent clearance of the drug from the serum, calculated as the drug dose divided area under the curve from time 0 extrapolated to infinite time [AUC (0-inf)]. | Baseline to week 24 | 
| Apparent Volume of Distribution After Extravascular Administration (Vd/F) of Nemolizumab | Vd/F was calculated as dose divided by lambda_z *AUC(0-inf). | Baseline to week 24 | 
| Population Lag Time (Tlag) | Lag time is defined as the time taken for a drug to appear in the systemic circulation following administration. The population Tlag value was estimated for the overall population and was reported in this endpoint. | Baseline to week 24 | 
| First Order Constant of Absorption (ka) | PK of Nemolizumab was evaluated in participants using Ka using PK samples collected on Weeks 1-2, 4, 8, 12, 16 and 24. Ka was evaluated by population PK (popPK) methods and mean and standard from the model has been tabulated. | Baseline to week 24 | 
| Maximum Observed Serum Concentration (Cmax) of Nemolizumab | Cmax was obtained from serum concentration time curve. | Baseline to week 12 | 
| Time to Reach Maximum Observed Serum Concentration (Tmax) of Nemolizumab | Time to reach maximum observed serum concentration (Tmax) for Nemolizumab was derived from serum concentrations versus time data. | Baseline to week 12 | 
| Trough Serum Concentration (Ctrough) of Nemolizumab at Week 4 | Ctrough is the concentration prior to study drug administration. | At week 4 | 
| Trough Serum Concentration (Ctrough) of Nemolizumab at Week 8 | Ctrough is the concentration prior to study drug administration. | At week 8 | 
| Trough Serum Concentration (Ctrough) of Nemolizumab at Week 12 | Ctrough is the concentration prior to study drug administration. | At week 12 | 
| Trough Serum Concentration (Ctrough) of Nemolizumab at Week 16 | Ctrough is the concentration prior to study drug administration. | At week 16 | 
| Area Under the Serum Concentration-Time Curve From Zero to 4 Week Post-dose (AUC0-4w) | Area under the drug concentration-time curve from 0 to 4 week post dosing for Nemolizumab. AUC(0-4w) was calculated according to the mixed log-linear trapezoidal rule. | Pre-dose through 4 weeks post-dose | 
| Area Under the Serum Concentration-Time Curve From Time Zero to 8 Week Post-dose (AUC0-8w) | Area under the drug concentration-time curve from 0 to 8 week post dosing for Nemolizumab. AUC(0-8w) was calculated according to the mixed log-linear trapezoidal rule. | Pre-dose through 8 weeks post-dose | 
| Area Under the Serum Concentration-Time Curve From Time Zero to 12 Week Post-dose (AUC0-12w) | Area under the drug concentration-time curve from 0 to 12 week post dosing for Nemolizumab. AUC(0-12w) was calculated according to the mixed log-linear trapezoidal rule. | Pre-dose through 12 week post-dose | 
| Area Under the Serum Concentration-Time Curve From Time Zero to 16 Week Post-dose (AUC0-16w) | Area under the drug concentration-time curve from 0 to 16 week post dosing for Nemolizumab. AUC(0-16w) was calculated according to the mixed log-linear trapezoidal rule. | Pre-dose through 16 weeks post-dose | 
| Apparent Terminal Half-life (t1/2) | Apparent Terminal Half-life (t1/2) is the time required for a given drug concentration in the serum to decrease by 50%. | Baseline to week 24 | 
| Number of Participants With Treatment-Related Positive Anti-Drug Antibodies (ADA) in Serum at Week 4 | Antidrug antibodies were determined using a validated enzyme-linked immunosorbent assay (ELISA) assay. Number of participants with positive ADA in Serum were reported. | At week 4 | 
| Number of Participants With Neutralizing Antibodies | The number of participants with neutralizing antibodies response at time of baseline up to week 24 has been presented. Neutralizing antibodies response assay result have been only presented for participants with positive anti-drug antibody assay. | Baseline up to Week 24 | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Adverse Event of Special Interests (AESI) and Serious Adverse Events (SAEs) | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAEs is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAE was defined as AEs starting/worsening after first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs. An AESI is a noteworthy event for study drug that should be monitored closely and reported immediately. The following AEs will be considered AESIs: Anaphylactic reactions, Acute allergic reactions requiring treatment, Severe injection site reaction, Newly-diagnosed asthma or worsening of asthma, Peripheral edema: limbs, bilateral and Facial edema. | Baseline through week 24 | 
| Number of Participants With Asthma Control Test (ACT) Score Less Than or Equal to (=<) 19 at Week 1-2 | The ACT is a participant-completed assessment consisting of 5 questions health survey for measuring asthma control. Each question is answered with a score in a range of 1 to 5 and lower score represents the more severe condition. The scale range for Question 1 is all the time (1) to none of the time (5); Question 2 range: more than once a day (1) to not at all (5); Question 3 range: 4 or more nights a week (1) to not at all (5); Question 4 range: 3 or more times per day (1) to not at all (5); Question 5 range: not controlled at all (1) to completely controlled (5). A total ACT score is obtained as the sum of the 5 individual question scores that is from 5 to 25, where Higher scores mean that asthma is more controlled. | At week 1-2 | 
| Number of Participants With Asthma Control Test (ACT) Score Less Than or Equal to (=<) 19 at Week 4 | The ACT is a participant-completed assessment consisting of 5 questions health survey for measuring asthma control. Each question is answered with a score in a range of 1 to 5 and lower score represents the more severe condition. The scale range for Question 1 is all the time (1) to none of the time (5); Question 2 range: more than once a day (1) to not at all (5); Question 3 range: 4 or more nights a week (1) to not at all (5); Question 4 range: 3 or more times per day (1) to not at all (5); Question 5 range: not controlled at all (1) to completely controlled (5). A total ACT score is obtained as the sum of the 5 individual question scores that is from 5 to 25, where Higher scores mean that asthma is more controlled. | At week 4 | 
| Number of Participants With Asthma Control Test (ACT) Score Less Than or Equal to (=<) 19 at Week 8 | The ACT is a participant-completed assessment consisting of 5 questions health survey for measuring asthma control. Each question is answered with a score in a range of 1 to 5 and lower score represents the more severe condition. The scale range for Question 1 is all the time (1) to none of the time (5); Question 2 range: more than once a day (1) to not at all (5); Question 3 range: 4 or more nights a week (1) to not at all (5); Question 4 range: 3 or more times per day (1) to not at all (5); Question 5 range: not controlled at all (1) to completely controlled (5). A total ACT score is obtained as the sum of the 5 individual question scores that is from 5 to 25, where Higher scores mean that asthma is more controlled. | At week 8 | 
| Number of Participants With Asthma Control Test (ACT) Score Less Than or Equal to (=<) 19 at Week 12 | The ACT is a participant-completed assessment consisting of 5 questions health survey for measuring asthma control. Each question is answered with a score in a range of 1 to 5 and lower score represents the more severe condition. The scale range for Question 1 is all the time (1) to none of the time (5); Question 2 range: more than once a day (1) to not at all (5); Question 3 range: 4 or more nights a week (1) to not at all (5); Question 4 range: 3 or more times per day (1) to not at all (5); Question 5 range: not controlled at all (1) to completely controlled (5). A total ACT score is obtained as the sum of the 5 individual question scores that is from 5 to 25, where Higher scores mean that asthma is more controlled. | At week 12 | 
| Number of Participants With Clinically Significant Abnormalities in Physical Examination (PE) Findings | A complete PE included assessments of the head, ears, eyes, nose, throat, neck (including thyroid), skin/integumentary system, cardiovascular system, respiratory system, gastrointestinal system, musculoskeletal system, lymph nodes, and nervous system. Clinical significance was determined by the investigator. | Baseline up to Week 24 | 
| Number of Participants With Clinically Significant Abnormalities in Laboratory Values | Laboratory investigation included hematology, biochemistry, and urinalysis. Clinical significance was determined by the investigator. The number of participants with clinically significant abnormalities in laboratory parameters were reported. | Baseline up to Week 24 | 
| Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings at Week 16 | The ECG recordings were obtained after 10 minutes of rest in a semi-supine position. Number of participants with clinically significant change from baseline in ECG findings were reported. Clinically significance was decided by investigator. | At week 16 | 
| Number of Participants With Clinically Significant Abnormalities in Vital Signs | Vital signs included pulse rate, systolic and diastolic blood pressure (after the participant had been sitting for at least 5 minutes), and body temperature. Clinically significance was decided by investigator.. | Baseline up to Week 24 | 
| Number of Participants With Abnormal Peak Expiratory Flow (PEF) <80% of Predicted Value at Week 1-2 | PEF was the maximum speed of expiration measured using spirometer. A participant took rest just before the measurement. At each time of measurement, a participant expired for at least 6 seconds wherever possible. At each time of measurement, at least 3 readings were obtained, and three readings which were obtained in an appropriate manner were stored. PEF <80% of predictive value is considered as abnormal. | At week 1-2 | 
| Number of Participants With Abnormal Peak Expiratory Flow (PEF) <80% Predicted Value at Week 4 | PEF was the maximum speed of expiration measured using spirometer. A participant took rest just before the measurement. At each time of measurement, a participant expired for at least 6 seconds wherever possible. At each time of measurement, at least 3 readings were obtained, and three readings which were obtained in an appropriate manner were stored. PEF <80% of predictive value is considered as abnormal. | At week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-Compartmental Analysis: Area Under the Serum Concentration-time Curve From Time Zero to 4 Weeks Post-dose AUC(0-4w) | Area under the drug concentration-time curve from 0 to 4 week post dosing for Nemolizumab. AUC(0-4w) was calculated according to the mixed log-linear trapezoidal rule. | Pre-dose through 4 weeks post-dose | 
| Non-Compartmental Analysis: Area Under the Serum Concentration-Time Curve From Time Zero to 8 Week Post-dose (AUC0-8w) | Area under the drug concentration-time curve from 0 to 8 week post dosing for Nemolizumab. AUC(0-8w) was calculated according to the mixed log-linear trapezoidal rule. | Pre-dose through 8 weeks post-dose | 
| Non-Compartmental Analysis: Area Under the Serum Concentration-Time Curve From Time Zero to 12 Week Post-dose (AUC0-12w) | Area under the drug concentration-time curve from 0 to 12 week post dosing for Nemolizumab. AUC(0-12w) was calculated according to the mixed log-linear trapezoidal rule | Pre-dose through 12 week post-dose | 
| Non-Compartmental Analysis: Area Under the Serum Concentration-Time Curve From Time Zero to 16 Week Post-dose (AUC0-16w) | Area under the drug concentration-time curve from 0 to 16 week post dosing for Nemolizumab. AUC(0-16w) was calculated according to the mixed log-linear trapezoidal rule. | Pre-dose through 16 weeks post-dose | 
| Absolute Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16 | EASI assesses severity and extent of atopic dermatitis (AD) signs through a composite score of erythema, induration/population, excoriation, and lichenification. Each characteristic was assessed for severity on a scale of 0 (absent) to 3 (severe) for each of the 4 body areas: head/neck, trunk, upper limbs, and lower limbs. The total EASI score range from 0 to 72 with higher scores representing greater severity of AD. | Baseline, Week 16 | 
| Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16 | EASI assesses severity and extent of AD signs through a composite score of erythema, induration/population, excoriation, and lichenification. Each characteristic was assessed for severity on a scale of 0 (absent) to 3 (severe) for each of the 4 body areas: head/neck, trunk, upper limbs, and lower limbs. The EASI score can range from 0 to 72 with higher scores representing greater severity of AD. | Baseline, Week 16 | 
| Number of Participants Who Achieved Investigator's Global Assessment (IGA) Success (Defined as IGA 0 [Clear] or 1 [Almost Clear]) From Baseline to Week 16 | IGA is a 5-point scale used by the investigator or trained designee to evaluate the global severity of AD. Ranging from (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe), where higher score indicated higher severity. IGA success is defined as participants with 0 (clear) or 1 (almost clear) and at least 2 -grade improvement from baseline. Number of Participants who achieved Investigator's Global Assessment (IGA) Success from baseline to week 16 were reported. | Baseline to Week 16 | 
| Change From Baseline in the Percentage of Body Surface Area (BSA) Involvement by Atopic Dermatitis (AD) at Each Visit up to Week 24 | BSA affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck [9%], anterior trunk [18%], back [18%], upper limbs [18%], lower limbs [36%], and genitals [1%]) and reported as a percentage of all major body sections combined. The reported percentage of BSA was combined percentage of all major body sections. | Baseline, Week 1-2, 4, 8, 12, 14, 16 and 24 | 
| Absolute Change From Baseline in Weekly Average of Peak Pruritus Numeric Rating Scale (NRS) Score at Week 16 | Pruritus NRS is a scale that was used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]), higher scores indicated greater severity. | Baseline, Week 16 | 
| Percent Change From Baseline in Weekly Average of Peak Pruritus Numeric Rating Scale (NRS) Score at Week 16 | Pruritus NRS is a scale that was used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]), higher scores indicated greater severity. | Baseline, Week 16 | 
| Absolute Change From Baseline in Weekly Average of Average Pruritus Numeric Rating Scale (NRS) Score at Week 16 | Pruritus NRS is a scale that was used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]), higher scores indicated greater severity. | Baseline, Week 16 | 
| Percent Change From Baseline in Weekly Average of Average Pruritus Numeric Rating Scale (NRS) Score at Week 16 | Pruritus NRS is a scale that was used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]), higher scores indicated greater severity. | Baseline, Week 16 | 
| Absolute Change From Baseline in Weekly Average Sleep Disturbance Numeric Rating Scale (NRS) Score at Week 16 | The sleep disturbance NRS is a scale used by the participants to report the degree of their sleep loss related to AD. Participants were 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 16 | 
| Percent Change From Baseline in Weekly Average Sleep Disturbance Numeric Rating Scale (NRS) Score at Week 16 | The sleep disturbance NRS is a scale used by the participants to report the degree of their sleep loss related to AD. Participants were 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 16 | 
| Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 16 | Scoring Atopic Dermatitis (SCORAD) is a validated measure commonly used to assess the severity and the extent of AD signs and symptoms. SCORAD is a clinical tool for assessing the severity and the extent of AD signs and symptoms. Extent and intensity of six types of basic lesions (erythema/darkening, edema/papule, oozing/crusting, excoriation, lichenification/prurigo and dryness) and symptoms (itching and loss of sleep) were assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). | Baseline, Week 16 | 
| Number of Topical Atopic Dermatitis Medication-Free Days Through Week 24 | Number of topical AD medication-free days through Week 16 was calculated as the number of days that a participant used neither topical corticosteroid (TCS)/ topical calcineurin inhibitors (TCI) nor system rescue therapy divided by the study days. | Baseline through Week 24 | 
| Dermatology Life Quality Index (DLQI) For Participants > 16 Years of Age at Baseline and Week 16 | The DLQI is a validated 10-item questionnaire covering domains including symptoms/feelings, daily activities, leisure, work/school, personal relationships, and treatment. The participants were rate each question ranging from 0 (not at all) to 3 (very much) and overall score ranges from 0 to 30. A higher total score indicates a poorer quality of life (QoL). | Baseline, Week 16 | 
| Children's Dermatology Life Quality Index (cDLQI) For Participants 12-16 Years of Age at Baseline and Week 16 | The DLQI is a validated 10-item questionnaire covering domains including symptoms/feelings, daily activities, leisure, work/school, personal relationships, and treatment. The participants were rate each question ranging from 0 (not at all) to 3 (very much) and overall score ranges from 0 to 30. A higher total score indicates a poorer quality of life (QoL). | Baseline, Week 16 | 

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