The purpose of this study was to evaluate the pharmacokinetics and safety of nemolizumab in adolescent participants with AD.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
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.
Galderma Investigational Site
Fountain Valley, California, United States
Galderma Investigational Site
Fremont, California, United States
Galderma Investigational Site
Jacksonville, Florida, United States
Nemolizumab Serum Concentrations at Week 1-2
Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA).
Time frame: At week 1-2
Nemolizumab Serum Concentrations at Week 4
Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA).
Time frame: At week 4
Nemolizumab Serum Concentrations at Week 8
Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA).
Time frame: At week 8
Nemolizumab Serum Concentrations at Week 12
Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA).
Time frame: At week 12
Nemolizumab Serum Concentrations at Week 16
Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA).
Time frame: At week 16
Nemolizumab Serum Concentrations at Week 24
Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA).
Time frame: 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 \[AUC (0-inf)\].
Time frame: Baseline to week 24
Apparent Volume of Distribution After Extravascular Administration (Vd/F) of Nemolizumab
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Galderma Investigational Site
Tampa, Florida, United States
Galderma Investigational Site
Columbus, Georgia, United States
Galderma Investigational Site
Sandy Springs, Georgia, United States
Galderma Investigational Site
Gresham, Oregon, United States
Galderma Investigational Site
Dallas, Texas, United States
Galderma Investigational Site
Frisco, Texas, United States
Galderma Investigational Site
Richmond, Virginia, United States
Vd/F was calculated as dose divided by lambda\_z \*AUC(0-inf).
Time frame: 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.
Time frame: 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.
Time frame: Baseline to week 24
Maximum Observed Serum Concentration (Cmax) of Nemolizumab
Cmax was obtained from serum concentration time curve.
Time frame: 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.
Time frame: Baseline to week 12
Trough Serum Concentration (Ctrough) of Nemolizumab at Week 4
Ctrough is the concentration prior to study drug administration.
Time frame: At week 4
Trough Serum Concentration (Ctrough) of Nemolizumab at Week 8
Ctrough is the concentration prior to study drug administration.
Time frame: At week 8
Trough Serum Concentration (Ctrough) of Nemolizumab at Week 12
Ctrough is the concentration prior to study drug administration.
Time frame: At week 12
Trough Serum Concentration (Ctrough) of Nemolizumab at Week 16
Ctrough is the concentration prior to study drug administration.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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%.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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..
Time frame: 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.
Time frame: 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.
Time frame: At week 4
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.
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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).
Time frame: 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).
Time frame: Baseline, Week 16