A Pharmacokinetics and Safety Study of Nemolizumab in Adolescent Participants With Atopic Dermatitis (AD)
- Conditions
- Atopic Dermatitis
- Interventions
- Biological: Nemolizumab
- Registration Number
- NCT03921411
- Lead Sponsor
- Galderma R&D
- Brief Summary
The purpose of this study was to evaluate the pharmacokinetics and safety of nemolizumab in adolescent participants with AD.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Nemolizumab Nemolizumab Nemolizumab
- Primary Outcome Measures
Name Time Method First Order Constant of Absorption (ka) Baseline to week 24 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.
Population Lag Time (Tlag) Baseline to week 24 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.
Nemolizumab Serum Concentrations at Week 8 At week 8 Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA).
Apparent Clearance After Extravascular Administration (Cl/F) of Nemolizumab Baseline to week 24 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 \[AUC (0-inf)\].
Nemolizumab Serum Concentrations at Week 4 At week 4 Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA).
Nemolizumab Serum Concentrations at Week 24 At week 24 Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA).
Apparent Volume of Distribution After Extravascular Administration (Vd/F) of Nemolizumab Baseline to week 24 Vd/F was calculated as dose divided by lambda_z \*AUC(0-inf).
Maximum Observed Serum Concentration (Cmax) of Nemolizumab Baseline to week 12 Cmax was obtained from serum concentration time curve.
Time to Reach Maximum Observed Serum Concentration (Tmax) of Nemolizumab Baseline to week 12 Time to reach maximum observed serum concentration (Tmax) for Nemolizumab was derived from serum concentrations versus time data.
Trough Serum Concentration (Ctrough) of Nemolizumab at Week 8 At week 8 Ctrough is the concentration prior to study drug administration.
Trough Serum Concentration (Ctrough) of Nemolizumab at Week 16 At week 16 Ctrough is the concentration prior to study drug administration.
Nemolizumab Serum Concentrations at Week 16 At week 16 Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA).
Area Under the Serum Concentration-Time Curve From Time Zero to 8 Week Post-dose (AUC0-8w) Pre-dose through 8 weeks post-dose 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.
Nemolizumab Serum Concentrations at Week 1-2 At week 1-2 Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA).
Nemolizumab Serum Concentrations at Week 12 At week 12 Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA).
Area Under the Serum Concentration-Time Curve From Zero to 4 Week Post-dose (AUC0-4w) Pre-dose through 4 weeks post-dose 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.
Number of Participants With Asthma Control Test (ACT) Score Less Than or Equal to (=<) 19 at Week 4 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.
Area Under the Serum Concentration-Time Curve From Time Zero to 12 Week Post-dose (AUC0-12w) Pre-dose through 12 week post-dose 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.
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings at Week 16 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.
Trough Serum Concentration (Ctrough) of Nemolizumab at Week 4 At week 4 Ctrough is the concentration prior to study drug administration.
Trough Serum Concentration (Ctrough) of Nemolizumab at Week 12 At week 12 Ctrough is the concentration prior to study drug administration.
Number of Participants With Abnormal Peak Expiratory Flow (PEF) <80% Predicted Value at Week 4 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.
Number of Participants With Treatment-Related Positive Anti-Drug Antibodies (ADA) in Serum at Week 4 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.
Apparent Terminal Half-life (t1/2) Baseline to week 24 Apparent Terminal Half-life (t1/2) is the time required for a given drug concentration in the serum to decrease by 50%.
Area Under the Serum Concentration-Time Curve From Time Zero to 16 Week Post-dose (AUC0-16w) Pre-dose through 16 weeks post-dose 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.
Number of Participants With Neutralizing Antibodies Baseline up to Week 24 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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Adverse Event of Special Interests (AESI) and Serious Adverse Events (SAEs) Baseline through week 24 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.
Number of Participants With Asthma Control Test (ACT) Score Less Than or Equal to (=<) 19 at Week 1-2 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.
Number of Participants With Asthma Control Test (ACT) Score Less Than or Equal to (=<) 19 at Week 8 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.
Number of Participants With Clinically Significant Abnormalities in Laboratory Values Baseline up to Week 24 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.
Number of Participants With Clinically Significant Abnormalities in Vital Signs Baseline up to Week 24 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..
Number of Participants With Abnormal Peak Expiratory Flow (PEF) <80% of Predicted Value at Week 1-2 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.
Number of Participants With Asthma Control Test (ACT) Score Less Than or Equal to (=<) 19 at Week 12 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.
Number of Participants With Clinically Significant Abnormalities in Physical Examination (PE) Findings Baseline up to Week 24 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.
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in Weekly Average of Average Pruritus Numeric Rating Scale (NRS) Score at Week 16 Baseline, 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.
Number of Topical Atopic Dermatitis Medication-Free Days Through Week 24 Baseline 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.
Dermatology Life Quality Index (DLQI) For Participants > 16 Years of Age at Baseline and Week 16 Baseline, 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).
Absolute Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16 Baseline, 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.
Absolute Change From Baseline in Weekly Average Sleep Disturbance Numeric Rating Scale (NRS) Score at Week 16 Baseline, 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.
Non-Compartmental Analysis: Area Under the Serum Concentration-Time Curve From Time Zero to 8 Week Post-dose (AUC0-8w) Pre-dose through 8 weeks post-dose 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.
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16 Baseline, 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.
Change From Baseline in the Percentage of Body Surface Area (BSA) Involvement by Atopic Dermatitis (AD) at Each Visit up to Week 24 Baseline, Week 1-2, 4, 8, 12, 14, 16 and 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.
Percent Change From Baseline in Weekly Average of Peak Pruritus Numeric Rating Scale (NRS) Score at Week 16 Baseline, 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.
Absolute Change From Baseline in Weekly Average of Average Pruritus Numeric Rating Scale (NRS) Score at Week 16 Baseline, 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.
Children's Dermatology Life Quality Index (cDLQI) For Participants 12-16 Years of Age at Baseline and Week 16 Baseline, 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).
Non-Compartmental Analysis: Area Under the Serum Concentration-Time Curve From Time Zero to 12 Week Post-dose (AUC0-12w) Pre-dose through 12 week post-dose 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
Absolute Change From Baseline in Weekly Average of Peak Pruritus Numeric Rating Scale (NRS) Score at Week 16 Baseline, 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.
Non-Compartmental Analysis: Area Under the Serum Concentration-time Curve From Time Zero to 4 Weeks Post-dose AUC(0-4w) Pre-dose through 4 weeks post-dose 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.
Non-Compartmental Analysis: Area Under the Serum Concentration-Time Curve From Time Zero to 16 Week Post-dose (AUC0-16w) Pre-dose through 16 weeks post-dose 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.
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 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.
Percent Change From Baseline in Weekly Average Sleep Disturbance Numeric Rating Scale (NRS) Score at Week 16 Baseline, 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.
Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 16 Baseline, 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).
Trial Locations
- Locations (1)
Galderma Investigational Site
🇺🇸Richmond, Virginia, United States