A Study Comparing Different Dosing Regimens of Ixekizumab (LY2439821) in Participants With Moderate to Severe Plaque Psoriasis

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the efficacy of ixekizumab dosing regimens in participants with plaque psoriasis.

Detailed Description
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The purpose of this study is to evaluate both the safety and efficacy of ixekizumab dosing regimens. There are 3 study periods: Screening Period, Blinded Treatment Dosing Period, and Post-Treatment Follow-Up.

Official Title
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A Multicenter, Randomized, Double-Blind Study Comparing the Efficacy and Safety of Ixekizumab Dosing Regimens in 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 psoriasis for at least 6 months prior to enrollment At least 10% BSA of psoriasis at screening and at enrollment sPGA score of at least 3 and PASI score of at least 12 at screening and at enrollment Candidates for phototherapy and/or systemic therapy Participant must agree to use reliable method of birth control during the study; women must continue using birth control for at least 12 weeks after stopping treatment Exclusion Criteria: Predominant pattern of pustular, erythrodermic, or guttate forms of psoriasis History of drug-induced psoriasis Cannot avoid excessive sun exposure or use of tanning booths for at least 4 weeks prior to enrollment and during the study Received systemic non-biologic psoriasis therapy or phototherapy within the previous 4 weeks; or had topical psoriasis treatment within the previous 2 weeks prior to enrollment Concurrent or recent use of any biologic agent Have participated in any study with ixekizumab Received a live vaccination within 12 weeks prior to enrollment Serious disorder or illness other than psoriasis Ongoing or serious infection within the last 12 weeks or evidence of tuberculosis Major surgery within 8 weeks of baseline, or will require surgery during the study Breastfeeding or nursing (lactating) women

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: 80 mg Ixekizumab Q2W<br>160 milligrams (mg) ixekizumab given as 2 subcutaneous (SQ) injections at baseline and then 80 mg ixekizumab given as 1 SQ injection every 2 weeks (Q2W) to week 52. Placebo administered SQ, Q2W to maintain blind. | Drug: Ixekizumab<br>* Administered SQ<br>* Other names: LY2439821;Drug: Placebo<br>* Administered SQ<br>|
| Experimental: 80 mg Ixekizumab Q4W<br>160 mg ixekizumab given as 2 SQ injections at baseline and then 80 mg ixekizumab given as 1 SQ injection every 4 weeks (Q4W) to week 52. Placebo administered SQ, Q2W to maintain blind. | Drug: Ixekizumab<br>* Administered SQ<br>* Other names: LY2439821;Drug: Placebo<br>* Administered SQ<br>|
| Experimental: 80 mg Ixekizumab Q4W/Q2W<br>160 mg ixekizumab given as 2 SQ injections at baseline and then 80 mg ixekizumab given as one SQ injection Q4W with step-up dosing to Q2W as needed (Q4W/Q2W step-up) to week 52. Placebo administered SQ, Q2W to maintain blind. | Drug: Ixekizumab<br>* Administered SQ<br>* Other names: LY2439821;Drug: Placebo<br>* Administered SQ<br>|
| Experimental: 80 mg Ixekizumab Q2W Maximum Extended Enrollment (ME2) Cohort<br>160 mg ixekizumab given as 2 SQ injections at baseline and then 80 mg ixekizumab given as 1 SQ injection Q2W to week 52. Placebo administered SQ, Q2W to maintain blind. | Drug: Ixekizumab<br>* Administered SQ<br>* Other names: LY2439821;Drug: Placebo<br>* Administered SQ<br>|
| Experimental: 80 mg Ixekizumab Q4W Maximum Extended Enrollment Cohort<br>160 mg ixekizumab given as 2 SQ injections at baseline and then 80 mg ixekizumab given as 1 SQ injection Q4W to week 52. Placebo administered SQ, Q2W to maintain blind. | Drug: Ixekizumab<br>* Administered SQ<br>* Other names: LY2439821;Drug: Placebo<br>* Administered SQ<br>|
| Experimental: 80 mg Ixekizumab Q4W/Q2W Maximum Extended Enrollment Cohort<br>160 mg ixekizumab given as 2 SQ injections at baseline and then 80 mg ixekizumab given as one SQ injection Q4W with step-up dosing to Q2W as needed (Q4W/Q2W step-up) to week 52. Placebo administered SQ, Q2W to maintain blind. | Drug: Ixekizumab<br>* Administered SQ<br>* Other names: LY2439821;Drug: Placebo<br>* Administered SQ<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Static Physician Global Assessment (sPGA) of (0,1) | The sPGA is the physician's determination of the participant's Psoriasis (Ps) lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participant's Ps was 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. Participants who did not meet the clinical response criteria or had missing data at Week 52 were considered non-responders for Non-Responder Imputation (NRI) analysis. | Week 52 | 
| Percentage of Participants Achieving 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) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no Ps to 72 for the most severe disease. 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 separately 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). Participants who did not meet the clinical response criteria or had missing data at Week52 were considered non-responders for NRI analysis. | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving sPGA (0) | 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. Participant's Ps was 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. Participants who did not meet the clinical response criteria or had missing data at Week 52 were considered non-responders for Non-Responder Imputation (NRI) analysis. | Week 52 | 
| Percentage of Participants Achieving PASI 90 | PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no Ps to 72 for the most severe disease. 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 separately 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 52 | 
| Percentage of Participants Achieving PASI 100 | The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no Ps to 72 for the most severe disease. 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 separately 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 52 | 
| Change From Baseline in PASI | The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no Ps to 72 for the most severe disease. Least Squares mean (LSmean) was calculated using Mixed-Effects Model of Repeated Measures (MMRM) analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured. | Baseline, Week 52 | 
| Percent Improvement in PASI | The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no Ps to 72 for the most severe disease. Least Squares mean (LSmean) was calculated using Mixed-Effects Model of Repeated Measures (MMRM) analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured. | Baseline, Week 52 | 
| Mean Change From Baseline in Percent Body Surface Area (BSA) Involvement | The percentage involvement of psoriasis on each participant's body surface area (BSA) was assessed by the investigator on a continuous 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 analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured. | Baseline, Week 52 | 
| Mean Change From Baseline in Nail Psoriasis Severity Index (NAPSI) Score | The NAPSI is a numeric, reproducible, objective tool for evaluation of fingernail (fn) Ps. This scale is used to evaluate the severity of fn bed Ps and fn matrix Ps by area of involvement in the fn unit. The fn is divided with imaginary horizontal and longitudinal lines into quadrants. Each fn is given a score for fn bed Ps (0 to 4) and fn matrix Ps (0 to 4) depending on presence (score of 1) or absence (score of 0) of any of the features of fn bed and fn matrix Ps in each quadrant. The NAPSI score of a fn is sum of scores in fn bed and 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 0 to 80 (0 indicates no Ps, 80 indicates worst Ps). LS mean was calculated using MMRM analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured. | Baseline, Week 52 | 
| Mean Change From Baseline in Psoriasis Scalp Severity Index (PSSI) Score | 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 change was calculated using MMRM analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured. | Baseline, Week 52 | 
| Mean Change From Baseline in Palmoplantar PASI (PPASI) | 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 PPASI) to 72 (most severe PPASI). The PPASI was only assessed if participants have palmoplantar psoriasis at baseline. LS mean was calculated using MMRM analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured. | Baseline, Week 52 | 
| Percentage of Participants Achieving an Itch Numeric Rating Scale (Itch NRS) ≥4 Point Reduction From Baseline | The Itch NRS is a participant-administered single-item 11-point horizontal scale anchored at 0 and 10, with 0 representing no itch and 10 representing 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. Participants who did not meet the clinical response criteria or had missing data at Week 52 were considered non-responders for Non-Responder Imputation (NRI) analysis. | Baseline, Week 52 | 
| Percentage of Participants Achieving Dermatology Life Quality Index (DLQI) Total Score of 0 and 1 (DLQI [0,1]) | 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). Participants who did not meet the clinical response criteria or had missing data at Week 52 were considered non-responders for Non-Responder Imputation (NRI) analysis. | Week 52 | 
| Change From Baseline in 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). LS mean change was calculated using MMRM analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured. | Baseline, Week 52 | 
| Change From Baseline in Itch NRS Score | The Itch NRS is a participant-administered single-item 11-point horizontal scale anchored at 0 and 10, with 0 representing no itch and 10 representing 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. LS mean change from baseline in PSSI was calculated using MMRM analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured. | Baseline, Week 52 | 
| Change From Baseline in Skin Pain Visual Analog Scale (VAS) | The pain VAS is a participant-administered single-item scale designed to measure Skin pain from Psoriasis using a 0-100 millimeter (mm) horizontal VAS. Overall severity of participant's skin pain from Psoriasis is indicated by placing a single mark on the horizontal 100 mm scale from 0 mm (no skin pain) to 100 mm (severe skin pain). LS mean was calculated using MMRM analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured. | Baseline, Week 52 | 
| Change From Baseline in European Quality of Life - 5 Dimensions 5 Level (EQ-5D-5L) VAS | EQ-5D-5L is a standardized measure of health status used to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L consists of 2 components: a descriptive system of the respondent's health and a rating of his/her current health state using a 0 (no pain) to 100mm VAS (severe pain). LS mean was calculated using MMRM analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured. | Baseline, Week 52 | 
| Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough,ss) of Ixekizumab | Trough concentrations at steady state of Ixekizumab were evaluated. | Predose, Week 4, 12, 24, 36 and 52 Post dose | 
| Number of Participants With Anti-Ixekizumab Antibodies | Number of participants with treatment-emergent positive anti-ixekizumab antibodies was summarized by treatment group. | Baseline through Week 52 |