A Study of Ixekizumab (LY2439821) in Chinese Participants 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 determine the efficacy and safety of the study drug ixekizumab in Chinese participants with moderate-to-severe plaque psoriasis.

Detailed Description
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Study I1F-MC-RHBH is a phase 3, multicenter, randomized, double-blind, placebo controlled, parallel-group study examining the effect of 2 dose regimens of ixekizumab versus placebo in participants with moderate-to-severe plaque psoriasis (Ps) during an induction dosing period with dosing for 12 weeks and the primary endpoint measured at 12 weeks, followed by a randomized, 48-week maintenance dosing period. During the maintenance dosing period, the study will evaluate the maintenance of response/remission, as well as relapse or rebound following treatment withdrawal, and response to retreatment following relapse.

Official Title
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A Multicenter Study With a Randomized, Double-Blind, Placebo-Controlled Induction Dosing Period Followed by a Randomized Maintenance Dosing Period to Evaluate the Efficacy and Safety of LY2439821 in Chinese Patients With Moderate-to-Severe Plaque Psoriasis

Conditions
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Plaque Psoriasis

Intervention / Treatment
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* Drug: Ixekizumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Present with chronic plaque Ps based on a confirmed diagnosis of chronic Ps vulgaris for at least 6 months prior to baseline. Have ≥10% BSA involvement at screening and baseline. Have both an sPGA score ≥3 and PASI score ≥12 at screening and baseline. Are candidates for phototherapy and/or systemic therapy. Exclusion Criteria: Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic and/or guttate psoriasis) at screening or baseline. Drug-induced psoriasis. Ongoing use of prohibited treatments. Have previously completed or withdrawn from this study, or have previously exposed to ixekizumab or any other biologic drug directly targeting interleukin-17 (IL-17) (such as secukinumab) or the IL-17 receptor. Have concurrent or recent use of any biologic agent within washout periods or <5 half-lives prior to baseline, whichever is longer. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ixekizumab 80mg Q4W<br>Participants received starting dose of 160 milligrams (mg) Ixekizumab at week 0 followed by 80mg Ixekizumab once every four weeks (Q4W) by subcutaneous injection during induction period. | Drug: Ixekizumab<br>* Administered SC<br>* Other names: LY2439821;|
| Experimental: Ixekizumab 80mg Q2W<br>Participants received starting dose of 160mg Ixekizumab at week 0 followed by 80mg Ixekizumab once every two weeks (Q2W) by subcutaneous injection during induction period. | Drug: Ixekizumab<br>* Administered SC<br>* Other names: LY2439821;Drug: Placebo<br>* Administered SC<br>|
| Placebo Comparator: Placebo<br>Participants received placebo every two weeks (Q2W) by subcutaneous (SC)injection during induction period. | Drug: Placebo<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 Static Physician Global Assessment (sPGA) Score of Clear (0) or Minimal (1) With at Least a 2 Point Improvement | The sPGA is the physician's determination of the participant's Ps lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participants Ps were assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe). An sPGA responder was defined as having a post-baseline sPGA score of 0 or 1 with at least a 2-point improvement from baseline. | Week 12 | 
| Percentage of Participants Achieving a ≥75% Improvement in Psoriasis Area and Severity Index (PASI 75) | The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored by itself and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no Ps) to 72 (the most severe disease). | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving a Static Physician Global Assessment (sPGA) Score of Clear (0) (Remission) | The sPGA is the physician's determination of the participant's Ps lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participants Ps were assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe). An sPGA assessed as 0, indicates complete resolution of plaque Ps. | Week 12 | 
| Percentage of Participants Achieving a ≥90% Improvement in Psoriasis Area and Severity Index (PASI 90) | The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored by itself and the scores were then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no Ps) to 72 (the most severe disease). | Week 12 | 
| Percentage of Participants Achieving a 100% Improvement in Psoriasis Area and Severity Index (PASI 100) | The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored by itself and the scores were then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no Ps) to 72 (the most severe disease). | Week 12 | 
| Percentage of Participants Achieving an Itch Numeric Rating Scale (NRS) ≥4 Point Reduction From Baseline for Participants Who Had Baseline Itch NRS ≥4 | The Itch NRS is a participant-administered, 11-point horizontal scale anchored at 0 (no itch) and 10 (worst itch imaginable). Overall severity of a participant's itching from Ps is indicated by circling the number that best describes the worst level of itching in the past 24 hours. | Week 12 | 
| Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score | The DLQI is a simple, participant-administered, 10 question, validated, quality-of-life questionnaire that covers 6 domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include not at all, a lot, and very much, with corresponding scores of 1, 2, and 3, respectively, and unanswered (not relevant) responses scored as 0. Totals range from 0 to 30 (less to more impairment). A score of 0 or 1 indicates no impact of disease on a participants quality of life. Least Square Mean (LS Mean) was calculated using Mixed Model Repeated Measures (MMRM) model includes treatment, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors. | Baseline, Week 12 | 
| Change From Baseline in Nail Psoriasis Severity Index (NAPSI) Score in Participants With Baseline Fingernail Involvement | NAPSI is a numeric, reproducible, objective tool for evaluation of fingernail(fn) Ps. This scale is used to evaluate severity of fn bed Ps & fn matrix Ps by area of involvement in the fn unit. fn is divided with imaginary horizontal & longitudinal lines into quadrants. Each fn is given a score for fn bed Ps 0(none) to 4(Ps in 4 quadrants of the fn) & fn matrix Ps 0(none) to 4(Ps in 4 quadrants in matrix), depending on presence (score of 1) or absence (score of 0) of any of the features of fn bed or matrix Ps in each quadrant.NAPSI score of a fn is sum of scores in fn bed & fn matrix from each quadrant (maximum of 8). Each fn is evaluated, then the sum of all fn equals the total NAPSI score with a range from range 0 to 80. Higher scores indicate more severe ps. LS Mean was calculated using MMRM model includes treatment, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors. | Baseline, Week 12 | 
| Change From Baseline in Percent of Body Surface Area (BSA) Involvement of Psoriasis | The percentage involvement of psoriasis on each participant's body surface area was assessed by the investigator on a scale from 0% (no involvement) to 100% (full involvement), in which 1% corresponds to the size of the participant's hand including palm, fingers and thumb. LS Mean was calculated using MMRM model includes treatment, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors. | Baseline, Week 12 | 
| Change From Baseline in Psoriasis Scalp Severity Index (PSSI) Score in Participants With Baseline Scalp Involvement | The PSSI is a physician assessment of erythema, induration and desquamation and percent of scalp that is covered with a scores range from 0 (none) to 4 (very severe). The composite score is derived from the sum of scores for erythema, induration, and desquamation multiplied by the score recorded for the extent of the scalp area involved, 1 (<10%) to 6 (90%-100%) with a total score ranging from 0 (less severity) to 72 (more severity). LS Mean was calculated using MMRM model includes treatment, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors. | Baseline, Week 12 | 
| Change From Baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score | The SF-36 is a participant-reported outcome measure evaluating participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. Items from 8 domains contribute to the PCS. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. LS Mean was calculated using MMRM model includes treatment, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors. | Baseline, Week 12 | 
| Change From Baseline in Medical Outcomes Study SF-36 Mental Component Summary (MCS) Score | The SF-36 is a participant-reported outcome measure evaluating participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. Items from 8 domains contribute to the PCS. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. LS Mean was calculated using MMRM model includes treatment, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors. | Baseline, Week 12 | 
| Change From Baseline on Patient Global Assessment of Disease Severity | The Patient Global Assessment of Disease Severity is a single-item participant-reported outcome measure on which participants are asked to rate the severity of their psoriasis today from 0 (Clear) = no psoriasis, to 5 (Severe) = the worst their psoriasis has ever been. LS Mean was calculated using MMRM model includes treatment, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors. | Baseline, Week 12 | 
| Change From Baseline in Palmoplantar PASI (PPASI) in Participants With Baseline Palmoplantar Involvement | The Palmoplantar PASI is a composite score derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement, ranging from 0 (no Ps) to 72. (the most severe disease) The PPASI was only assessed if participants have palmoplantar psoriasis at baseline. LS Mean was calculated using MMRM model includes treatment, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors. | Baseline, Week 12 | 
| Change From Baseline on the Joint Pain Visual Analog Scale (VAS) | The Joint Pain VAS is a participant-administered scale designed to measure current joint pain from PsA using a 100-mm horizontal VAS. Overall severity of a participant's joint pain from PsA is indicated by placing a single mark on the horizontal scale (0 = none; 100 = as severe as you can imagine). LS Mean was calculated using MMRM model includes treatment, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors. | Baseline, Week 12 | 
| Percentage of Participants With Anti-Ixekizumab Antibodies | Percentage was calculated based on the number of evaluable participants and was calculated by number of participants with treatment-emergent positive anti-ixekizumab antibodies / number of evaluable participants * 100%. | Baseline through Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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skin lesions, scaly patches, plaque psoriasis, ixekizumab, skin condition, skin disease, itching, psoriasis vulgaris, immune-mediated systemic disease, papules