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

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

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

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

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

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

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

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)].

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

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.

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.

Cmax was obtained from serum concentration time curve.

Time to reach maximum observed serum concentration (Tmax) for Nemolizumab was derived from serum concentrations versus time data.

Ctrough is the concentration prior to study drug administration.

Ctrough is the concentration prior to study drug administration.

Ctrough is the concentration prior to study drug administration.

Ctrough is the concentration prior to study drug administration.

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.

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.

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.

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) is the time required for a given drug concentration in the serum to decrease by 50%.

Antidrug antibodies were determined using a validated enzyme-linked immunosorbent assay (ELISA) assay. Number of participants with positive ADA in Serum were reported.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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..

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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).

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).