A Study of Mirikizumab (LY3074828) 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 the study drug mirikizumab in participants with moderate to severe plaque psoriasis.

Official Title
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A Phase 2, Multicenter, Randomized, Parallel-Arm, Placebo- Controlled Study of LY3074828 in Subjects With Moderate-to- Severe Plaque Psoriasis

Conditions
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Plaque Psoriasis

Intervention / Treatment
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* Drug: Mirikizumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Present with chronic plaque psoriasis based on an investigator confirmed diagnosis of chronic psoriasis vulgaris for at least 6 months prior to baseline and meet the following criteria: plaque psoriasis involving ≥10% body surface area (BSA) and absolute PASI score ≥12 in affected skin at screening and baseline sPGA score of ≥3 at screening and baseline Candidate for biologic treatment for psoriasis. Exclusion Criteria: Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute a risk when taking investigational product or could interfere with the interpretation of data. Breastfeeding or nursing (lactating) women. Have had serious, opportunistic, or chronic/recurring infection within 6 months prior to screening. Have received live vaccine(s) (included attenuated live vaccines) within 1 month of screening or intend to during the study. Have any other skin conditions (excluding psoriasis) that would affect interpretation of the results. Have received systemic nonbiologic psoriasis therapy or phototherapy within 28 days prior to baseline. Have received topical psoriasis treatment within 14 days prior to baseline. Have received anti-tumor necrosis factor (TNF) biologics, or anti-interleukin (IL)-17 targeting biologics within 8 weeks prior to baseline. Have previous exposure to any biologic therapy targeting IL-23 (including ustekinumab), either licensed or investigational (previous briakinumab use is permitted).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: 30 mg Mirikizumab<br>30 mg Mirikizumab administered subcutaneously (SC) every 8 weeks (Q8W). | Drug: Mirikizumab<br>* Administered SC<br>* Other names: LY3074828;|
| Experimental: 100 mg Mirikizumab<br>100 mg Mirikizumab administered SC Q8W. | Drug: Mirikizumab<br>* Administered SC<br>* Other names: LY3074828;|
| Experimental: 300 mg Mirikizumab<br>300 mg Mirikizumab administered SC Q8W. | Drug: Mirikizumab<br>* Administered SC<br>* Other names: LY3074828;|
| Placebo Comparator: Placebo<br>Placebo administered SC Q8W. | 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 ≥90% Improvement in Psoriasis Area and Severity Index (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 psoriasis (PsO) 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 PsO) to 72 (the most severe disease). | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With 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) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no PsO 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 PsO) to 72 (the most severe disease). | Week 16 | 
| Percentage of Participants With 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) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no PsO 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 PsO) to 72 (the most severe disease). | Week 16 | 
| Percentage of Participants With a Static Physician Global Assessment (sPGA) 0 and 0/1 | The sPGA is the physician's determination of the participant's PsO lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participant's PsO 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 16 were considered non-responders for non-responder Imputation (NRI) analysis. | Week 16 | 
| Mean Change From Baseline on the Psoriasis Symptom Scale (PSS) Total Score | PSS is a patient-administered assessment of 4 symptoms (itch, pain, stinging, and burning); 3 signs (redness, scaling, and cracking); and 1 item on the discomfort related to symptoms/signs. The overall severity for each individual symptom/sign from the patient's psoriasis is indicated by selecting the number from a numeric rating scale (NRS) of 0 to 10 that best describes the worst level of each symptom/sign in the past 24 hours, where 0=no symptom/sign and 10=worst imaginable symptom/sign. The total score was calculated by summing the 8 individual items and ranged from 0 to 80, higher scores indicated greater symptom/sign severity. Least Square(LS) Mean was calculated using Mixed Model Repeated Measures (MMRM) model with treatment, geographic region [United States/Outside United States (US/OUS)], previous therapy (yes/no), baseline value, visit, and the interaction treatment-by-visit as fixed factors, covariance structure = heterogeneous autoregressive. | Baseline, Week 16 | 
| Mean Change (Improvement) From Baseline on the Patient Global Assessment | The Patient's 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. Least Square (LS) Mean was calculated using Mixed Model Repeated Measures (MMRM) model with treatment, geographic region (US/OUS), previous therapy (yes/no), baseline value, visit, and the interaction treatment-by-visit as fixed factors, covariance structure = unstructured. | Baseline, Week 16 | 
| Mean Change From Baseline on the Dermatology Life Quality Index (DLQI) Total Score | The DLQI is a patient-reported, 10-question, quality-of-life questionnaire that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include Not at all, A little, A lot, and Very much, with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of Not relevant which is scored as 0. For all questions, if unanswered the question is scored as 0. Totals range from 0 to 30 (less to more impairment). Least Square (LS) Mean was calculated using Mixed Model Repeated Measures (MMRM) model with treatment, geographic region (US/OUS), previous therapy (yes/no), baseline value, visit, and the interaction treatment-by-visit as fixed factors, covariance structure = unstructured. | Baseline, Week 16 | 
| Mean Change From Baseline on the 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores | The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and 2 component scores (MCS and PCS). MCS consisted of social functioning, vitality, mental health, and role-emotional scales. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale with higher scores indicating better health status or functioning. Least Squares Mean (LS Mean) was calculated using Analysis of covariance (ANCOVA) model with treatment, geographic region (US/OUS), and previous therapy (yes/no) as fixed factors and baseline value as covariate. | Baseline, Week 16 | 
| Pharmacokinetics (PK): Area Under the Curve (AUC) of Mirikizumab From Baseline Through Week 104 | Pharmacokinetics (PK): Area Under the Curve (AUC) of Mirikizumab From Baseline through Week 104 | Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 52, Week 56, Week 64, Week 72, Week 80, Week 88, Week 96, Week 100, Week 104 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IL-23, dermatology