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

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of ixekizumab in pediatric participants with moderate-to-severe plaque psoriasis.

Official Title
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Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate Safety, Tolerability, and Efficacy of Ixekizumab in Patients From 6 to Less Than 18 Years of Age With Moderate-to-Severe Plaque Psoriasis

Conditions
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Plaque Psoriasis

Intervention / Treatment
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* Drug: Ixekizumab
* Drug: Placebo
* Drug: Etanercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of moderate-to-severe plaque-type psoriasis for at least 6 months prior to baseline as determined by the investigator. Have Psoriasis Area and Severity Index (PASI) score ≥12 and a Static Physician Global Assessment (sPGA) ≥3 and body surface area involvement ≥10% at screening and baseline. Are candidates for phototherapy or systemic treatment or considered by the investigator as not adequately controlled by topical therapies. Male subjects agree to use a reliable method of birth control during the study. Female subjects: Participants of childbearing age or childbearing potential who are sexually active who test negative for pregnancy must be counselled and agree to use either 1 highly effective method of contraception or 2 acceptable methods of contraception combined for the duration of the study and for at least 12 weeks following the last dose of study drug, or remain abstinent during the study and for at least 12 weeks following the last dose of study drug. Both the child or adolescent and a parent or legal guardian are able to understand and fully participate in the activities of the clinical study and sign their assent and consent, respectively. All immunizations are up-to-date in agreement with current immunization guidelines as noted by country specific paediatric authorities (e.g., the American Academy of Paediatrics). Note, subjects who are not up to date or have never been immunized are not to be enrolled in the trial. Exclusion Criteria: Have pustular, erythrodermic, and/or guttate forms of psoriasis. Have drug-induced psoriasis. Have clinical and/or laboratory evidence of untreated latent or active tuberculosis (TB). Participants with a documented history of immune deficiency syndrome. Have any other active or recent infection, including chronic or localized infections, within 4 weeks of baseline. Subjects with a known history of malignancy, lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy and/or splenomegaly unless ruled out by biopsy. Have used any therapeutic agent targeted at reducing interleukin-17. Have received other therapies within the specified time frames prior to screening (see below): adalimumab and infliximab 60 days, abatacept 90 days, anakinra 7 days, or any other biologic disease-modifying antirheumatic drug 5 half-lives. systemic therapy for psoriasis and psoriatic arthritis (PsA) (other than above, eg, methotrexate, cyclosporine), phototherapy (eg, photochemotherapy [psoralen plus ultraviolet A]) in the previous 4 weeks.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ixekizumab<br>Ixekizumab given subcutaneously (SC) during the double-blind treatment period and the open-label maintenance period. | Drug: Ixekizumab<br>* Administered SC<br>* Other names: LY2439821;|
| Placebo Comparator: Placebo<br>Placebo given SC during the double-blind treatment period and then ixekizumab given SC during the open-label maintenance period. | Drug: Placebo<br>* Administered SC<br>|
| Experimental: Open-Label Etanercept<br>Etanercept given SC during the double-blind treatment period and then ixekizumab given SC during the open-label maintenance period. Participants will only be randomized to etanercept in countries where it is approved for severe pediatric psoriasis treatment. | Drug: Etanercept<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a ≥75% Improvement in Psoriasis Area and Severity Index (PASI 75) (Placebo and Ixekizumab) | 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). | Week 12 | 
| Percentage of Participants With a Static Physician Global Assessment (sPGA) (0,1) (Placebo and Ixekizumab) | 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. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a ≥90% Improvement in Psoriasis Area and Severity Index (PASI 90) | 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). | Week 12 | 
| Percentage of Participants With a sPGA (0) | 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. | Week 12 | 
| Percentage of Participants With a 100% Improvement in Psoriasis Area and Severity Index (PASI 100) | 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). | Week 12 | 
| Percentage of Participants With a ≥75% Improvement in Psoriasis Area and Severity Index (PASI 75) | 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). | Week 4 | 
| Percentage of Participants With a Static Physician Global Assessment (sPGA) (0,1) | 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. | Week 4 | 
| Percentage of Participants With an Improvement of ≥4 in Those Who Had a Baseline Itch Numeric Rating Scale (NRS) Score of ≥4 | 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. | Week 12 | 
| Percentage of Participants Achieving Children's Dermatology Life Quality Index (CDLQI)/Dermatology Life Quality Index (DLQI) (0/1) | 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). | Week 12 | 
| Change From Baseline on the Nail Psoriasis Severity Index (NAPSI) | 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 = present in one quadrant of nail = present in two quadrants of nail = present in three quadrants of nail = 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) | Baseline, Week 12 | 
| Change From Baseline on the Psoriasis Scalp Severity Index (PSSI) | 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 = Slight = Moderate = Severe = Severest Possible Percent of Scalp Involved: = <10% = 10% - 29% = 30% - 49% = 50% - 69% = 70% - 89% = 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. | Baseline, Week 12 | 
| Change From Baseline on the Palmoplantar Psoriasis Severity Index (PPASI) | 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). | Baseline, Week 12 | 
| Number of Participants With Anti-Ixekizumab Antibodies | A treatment emergent - antidrug antibody (TE-ADA) positive participant were defined as: a participant with a >= 4-fold increase over a positive baseline antibody titer; or for a negative baseline titer, a participant with an increase from the baseline to a level of >= 1:10. | Baseline through Week 48 | 
| Pharmacokinetics (PK): Trough Ixekizumab Concentration at Steady State (Ctrough ss) | Pharmacokinetics (PK): Trough Ixekizumab Concentration at Steady State (Ctrough ss). | Week 12 | 
| Percentage of Participants With a ≥75% Improvement in Psoriasis Area and Severity Index (PASI 75) (Etanercept Approved Countries) | 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). | Week 12 | 
| Percentage of Participants With a Static Physician Global Assessment (sPGA) (0,1) (Etanercept Approved Countries) | 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. | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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children, psoriasis treatment, adolescents