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

Population Lag Time (Tlag)

时间窗: 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.

First Order Constant of Absorption (ka)

时间窗: 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.

Nemolizumab Serum Concentrations at Week 8

时间窗: 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

时间窗: 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

时间窗: At week 4

Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA).

Nemolizumab Serum Concentrations at Week 24

时间窗: 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

时间窗: Baseline to week 24

Vd/F was calculated as dose divided by lambda_z \*AUC(0-inf).

Maximum Observed Serum Concentration (Cmax) of Nemolizumab

时间窗: Baseline to week 12

Cmax was obtained from serum concentration time curve.

Time to Reach Maximum Observed Serum Concentration (Tmax) of Nemolizumab

时间窗: 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

时间窗: At week 8

Ctrough is the concentration prior to study drug administration.

Trough Serum Concentration (Ctrough) of Nemolizumab at Week 16

时间窗: At week 16

Ctrough is the concentration prior to study drug administration.

Nemolizumab Serum Concentrations at Week 16

时间窗: 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)

时间窗: 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

时间窗: At week 1-2

Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA).

Nemolizumab Serum Concentrations at Week 12

时间窗: 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)

时间窗: 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

时间窗: 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)

时间窗: 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

时间窗: 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

时间窗: At week 4

Ctrough is the concentration prior to study drug administration.

Trough Serum Concentration (Ctrough) of Nemolizumab at Week 12

时间窗: 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

时间窗: 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

时间窗: 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.

Area Under the Serum Concentration-Time Curve From Time Zero to 16 Week Post-dose (AUC0-16w)

时间窗: 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.

Apparent Terminal Half-life (t1/2)

时间窗: 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%.

Number of Participants With Neutralizing Antibodies

时间窗: 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)

时间窗: 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

时间窗: 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

时间窗: 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

时间窗: 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

时间窗: 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

时间窗: 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

时间窗: 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

时间窗: 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.