Study of Ixekizumab (LY2439821) in Children 6 to Less Than 18 Years With Moderate-to-Severe Plaque Psoriasis

PASI combines assessments of the extent of body surface involvement in 4 regions (head & neck(h), trunk(t), arms(u), legs(l)) & severity of scaling (S), redness (R), & plaque induration/infiltration (thickness, T) in each region. Severity is rated for each index (R, S, T) on a 0-4 scale (0 for no involvement up to 4 for severe involvement): 0 = none, 1 = slight, 2 = mild, 3 = moderate, 4 = severe Fraction of total body surface area (BSA) affected is graded on a 0-6 scale (0 for no involvement to 6 for 90% - 100% involvement): 0 = 0% (clear), 1 = \>0% to \<10%, 2 = 10% to \<30%, 3 = 30% to \<50%, 4 = 50% to \<70%, 5 = 70% to 90%, 6 = 90% to 100%. Overall score ranges from 0 (no psoriasis) to 72 (most severe disease).

Time frame: Week 12

Population: All randomized Participants in placebo and Ixekizumab arms. Missing values were imputed by Nonresponder imputation.~Participants who do not meet the clinical response criteria or have missing clinical response data or without at least 1 post-baseline observation are considered as nonresponders for NRI analysis.

Static Physician Global Assessment (sPGA): The physician's global assessment of the Participant's psoriasis lesions at a given time point. Plaques are assessed for induration, erythema, and scaling, and an overall rating of psoriasis severity is given using the anchors of clear (0), minimal (1), mild (2), moderate (3), severe (4), or very severe (5). An sPGA assessed as either 0 or 1 represents a clinically meaningful response of minimal plaque severity or complete resolution of plaque psoriasis.

Time frame: Week 12

Population: All randomized participants in placebo and Ixekizumab arms. Missing values were imputed by Nonresponder imputation(NRI).~Pts who do not meet the clinical response criteria or have missing clinical response data or without at least 1 post-baseline observation are considered as nonresponders for NRI analysis.

NAPSI is a numeric, reproducible, objective tool for evaluation of nail psoriasis. This scale was used to evaluate the severity of nail bed psoriasis & nail matrix psoriasis by area of involvement in the nail unit. Both fingernail & toenail involvement were assessed.The nail is divided with imaginary horizontal & longitudinal lines into quadrants. Each nail is given a score for nail bed psoriasis (0 to 4) & nail matrix psoriasis (0 to 4), depending on the presence (score of 1) or absence (score of 0) of any of the features of nail bed & nail matrix psoriasis in each quadrant: 0 = None 1. = present in one quadrant of nail 2. = present in two quadrants of nail 3. = present in three quadrants of nail 4. = present in four quadrants of nail NAPSI score of a nail is the sum of scores in nail bed & nail matrix from each quadrant (maximum of 8). Each nail is evaluated, & the sum of all the fingernails and toenails is the total NAPSI score ranging from 0 to 160 (No to Severe nail Psoriasis)

Time frame: Baseline, Week 12

Population: All randomized participants with baseline and post baseline NAPSI score in placebo and Ixekizumab arms.~Least squares(LS) Mean was calculated using mixed model repeated measures (MMRM) with treatment, region, baseline sPGA score,baseline weight category, baseline value, visit, treatment-by-visit, \& baseline-by-visit interactions as fixed factors.

PPASI was used if the participant has palmoplantar psoriasis at baseline. Both the palms & soles on each hand & foot was assessed for erythema, induration, desquamation & percentage of area affected as follows: Erythema (E), Induration (I), & Desquamation (D):0 = None, 1 = Slight, 2 = Moderate, 3 = Severe, 4 = Very Severe Percent of Palm and Sole Area Covered: 0 = None, 1 = \<10%, 2 = 10% - 29%, 3 = 30% - 49%, 4 = 50% - 69%, 5 = 70% - 89%, 6 = 90% - 100% PPASI score is a composite score derived from the sum scores for E, I, & D multiplied by a score for the extent of palm & sole area involvement. The range is 0 (no psoriasis) to 72 (most severe disease).

Time frame: Baseline, Week 12

Population: All randomized participants with baseline PPASI score in placebo and Ixekizumab arms.~LSMean was calculated using MMRM model with treatment, region, baseline sPGA score, baseline weight category, baseline value, visit, treatment-by-visit, and baseline-by-visit interactions as fixed factors.

The scalp was assessed for erythema (redness), induration (hardness), and desquamation (shedding of skin) and percentage of area affected as follows: Erythema, Induration and Desquamation: 0 = Absent 1. = Slight 2. = Moderate 3. = Severe 4. = Severest Possible Percent of Scalp Involved: 1. = \<10% 2. = 10% - 29% 3. = 30% - 49% 4. = 50% - 69% 5. = 70% - 89% 6. = 90% - 100% The PSSI score is a composite score derived from the sum of the scores for erythema, induration and desquamation multiplied by the score for the extent of scalp area involved (percent of scalp involved). The range is 0 (no psoriasis) to 72 (Most severe Disease). LSMean was calculated using treatment, region, baseline sPGA score, baseline weight category, baseline value, visit, treatment-by-visit, and baseline-by-visit interactions as fixed factors.

Time frame: Baseline, Week 12

Population: All randomized participants with baseline and post-baseline PSSI score in placebo and Ixekizumab.~LSMean was calculated using MMRM model with treatment, region, baseline sPGA score, baseline weight category, baseline value, visit, treatment-by-visit, and baseline-by-visit interactions as fixed factors.

A treatment emergent - antidrug antibody (TE-ADA) positive participant were defined as: 1. a participant with a \>= 4-fold increase over a positive baseline antibody titer; or 2. for a negative baseline titer, a participant with an increase from the baseline to a level of \>= 1:10.

Time frame: Baseline through Week 48

Population: All randomized participants from maintenance period (During maintenance period participants were on Ixekizumab treatment).

DLQI is a validated, dermatology-specific, patient reported measure that evaluates participant's health-related quality of life. It consists of 10 items that are grouped in 6 domains: symptoms & feelings, daily activities, leisure, work & school , personal relationships, & treatment. The recall period of this scale is over the last week. Response categories and corresponding scores are: Very much = 3, A lot = 2, A little = 1, Not at all = 0, Not relevant = 0. A DLQI total score is calculated by summing all 10 items responses, and has a range of 0 to 30 (higher scores are indicative of greater impairment). CDLQI questionnaire is designed for use in children (4 to 16 years of age). It consists of 10 items that are grouped into 6 domains: symptoms & feelings, leisure, school or holidays, personal relationships, sleep, & treatment. A CDLQI total score is calculated by summing all 10 items responses, and has a range of 0 to 30 (higher scores are indicative of greater impairment).

Time frame: Week 12

Population: All randomized participants in placebo and Ixekizumab arms. Missing values were imputed by Nonresponder imputation.~Participants who do not meet the clinical response criteria or have missing clinical response data or without at least 1 post-baseline observation are considered as nonresponders for NRI analysis.

PASI combines assessments of the extent of body surface involvement in 4 regions (head & neck(h), trunk(t), arms(u), legs(l)) & severity of scaling (S), redness (R), & plaque induration/infiltration (thickness, T) in each region. Severity is rated for each index (R, S, T) on a 0-4 scale (0 for no involvement up to 4 for severe involvement): 0 = none, 1 = slight, 2 = mild, 3 = moderate, 4 = severe Fraction of total BSA affected is graded on a 0-6 scale (0 for no involvement to 6 for 90% - 100% involvement): 0 = 0% (clear), 1 = \>0% to \<10%, 2 = 10% to \<30%, 3 = 30% to \<50%, 4 = 50% to \<70%, 5 = 70% to 90%, 6 = 90% to 100%. Overall score ranges from 0 (no psoriasis) to 72 (most severe disease).

Time frame: Week 12

Population: All randomized participants in placebo and Ixekizumab arms. Missing values were imputed by Nonresponder imputation.~Participants who do not meet the clinical response criteria or have missing clinical response data or without at least 1 post-baseline observation are considered as nonresponders for NRI analysis.

PASI combines assessments of the extent of body surface involvement in 4 regions (head & neck(h), trunk(t), arms(u), legs(l)) & severity of scaling (S), redness (R), & plaque induration/infiltration (thickness, T) in each region. Severity is rated for each index (R, S, T) on a 0-4 scale (0 for no involvement up to 4 for severe involvement): 0 = none, 1 = slight, 2 = mild, 3 = moderate, 4 = severe Fraction of total BSA affected is graded on a 0-6 scale (0 for no involvement to 6 for 90% - 100% involvement): 0 = 0% (clear), 1 = \>0% to \<10%, 2 = 10% to \<30%, 3 = 30% to \<50%, 4 = 50% to \<70%, 5 = 70% to 90%, 6 = 90% to 100%. Overall score ranges from 0 (no psoriasis) to 72 (most severe disease).

Time frame: Week 4

Population: All randomized participants in placebo and Ixekizumab arms. Missing values were imputed by Nonresponder imputation.~Pts who do not meet the clinical response criteria or have missing clinical response data or without at least 1 post-baseline observation are considered as nonresponders for NRI analysis.

PASI combines assessments of the extent of body surface involvement in 4 regions (head & neck(h), trunk(t), arms(u), legs(l)) & severity of scaling (S), redness (R), & plaque induration/infiltration (thickness, T) in each region. Severity is rated for each index (R, S, T) on a 0-4 scale (0 for no involvement up to 4 for severe involvement): 0 = none, 1 = slight, 2 = mild, 3 = moderate, 4 = severe Fraction of total BSA affected is graded on a 0-6 scale (0 for no involvement to 6 for 90% - 100% involvement): 0 = 0% (clear), 1 = \>0% to \<10%, 2 = 10% to \<30%, 3 = 30% to \<50%, 4 = 50% to \<70%, 5 = 70% to 90%, 6 = 90% to 100%. Overall score ranges from 0 (no psoriasis) to 72 (most severe disease).

Time frame: Week 12

Population: All randomized participants in Etanercept approved countries per protocol addendum. Missing values were imputed by Nonresponder imputation.~Participants who do not meet the clinical response criteria or have missing clinical response data or without at least 1 post-baseline observation are considered as nonresponders for NRI analysis.

PASI combines assessments of the extent of body surface involvement in 4 regions (head & neck(h), trunk(t), arms(u), legs(l)) & severity of scaling (S), redness (R), & plaque induration/infiltration (thickness, T) in each region. Severity is rated for each index (R, S, T) on a 0-4 scale (0 for no involvement up to 4 for severe involvement): 0 = none, 1 = slight, 2 = mild, 3 = moderate, 4 = severe Fraction of total BSA affected is graded on a 0-6 scale (0 for no involvement to 6 for 90% - 100% involvement): 0 = 0% (clear), 1 = \>0% to \<10%, 2 = 10% to \<30%, 3 = 30% to \<50%, 4 = 50% to \<70%, 5 = 70% to 90%, 6 = 90% to 100%.Overall score ranges from 0 (no psoriasis) to 72 (most severe disease).

Time frame: Week 12

Population: All randomized participants in placebo and Ixekizumab arms. Missing values were imputed by Nonresponder imputation.~Participants who do not meet the clinical response criteria or have missing clinical response data or without at least 1 post-baseline observation are considered as nonresponders for NRI analysis.

Itch Numeric Rating Scale (NRS): is a single-item, patient-reported outcome (PRO) measure designed to capture the overall severity of a participant's itching due to his/her psoriasis by having the patient circle the integer that describes the worst level of itching in the past 24 hours on an 11-point NRS anchored at 0 representing no itching and 10 representing worst itch imaginable.

Time frame: Week 12

Population: All randomized participants with baseline Itch NRS Score \>=4 in placebo and Ixekizumab arms.~Missing values were imputed by NRI. Participants who do not meet the clinical response criteria or have missing clinical response data or without at least 1 post-baseline observation are considered as nonresponders for NRI analysis.

Static Physician Global Assessment (sPGA): The physician's global assessment of the Participant's psoriasis lesions at a given time point. Plaques are assessed for induration, erythema, and scaling, and an overall rating of psoriasis severity is given using the anchors of clear (0), minimal (1), mild (2), moderate (3), severe (4), or very severe (5). An sPGA assessed as either 0 or 1 represents a clinically meaningful response of minimal plaque severity or complete resolution of plaque psoriasis. An sPGA assessed as 0 represents a clinically important endpoint indicating complete resolution of plaque psoriasis.

Time frame: Week 12

Population: All randomized participants in placebo and Ixekizumab arms. Missing values were imputed by Nonresponder imputation.~Participants who do not meet the clinical response criteria or have missing clinical response data or without at least 1 post-baseline observation are considered as nonresponders for NRI analysis.

Static Physician Global Assessment (sPGA): The physician's global assessment of the Participant's psoriasis lesions at a given time point. Plaques are assessed for induration, erythema, and scaling, and an overall rating of psoriasis severity is given using the anchors of clear (0), minimal (1), mild (2), moderate (3), severe (4), or very severe (5). An sPGA assessed as either 0 or 1 represents a clinically meaningful response of minimal plaque severity or complete resolution of plaque psoriasis.

Time frame: Week 4

Population: All randomized participants in placebo and Ixekizumab arms. Missing values were imputed by Nonresponder imputation.~Participants who do not meet the clinical response criteria or have missing clinical response data or without at least 1 post-baseline observation are considered as nonresponders for NRI analysis.

Static Physician Global Assessment (sPGA): The physician's global assessment of the Participant's psoriasis lesions at a given time point. Plaques are assessed for induration, erythema, and scaling, and an overall rating of psoriasis severity is given using the anchors of clear (0), minimal (1), mild (2), moderate (3), severe (4), or very severe (5). An sPGA assessed as either 0 or 1 represents a clinically meaningful response of minimal plaque severity or complete resolution of plaque psoriasis.

Time frame: Week 12

Population: All randomized participants in Etanercept approved countries per protocol addendum. Missing values were imputed by Nonresponder imputation.~Participants who do not meet the clinical response criteria or have missing clinical response data or without at least 1 post-baseline observation are considered as nonresponders for NRI analysis.

Pharmacokinetics (PK): Trough Ixekizumab Concentration at Steady State (Ctrough ss).

Time frame: Week 12

Population: All randomized participants in Ixekizumab arm with week 12 PK samples.