A Study of Ixekizumab (LY2439821) in Participants With Moderate-to-Severe Genital Psoriasis

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the efficacy and safety of the study drug ixekizumab compared to placebo in participants with moderate-to-severe genital psoriasis.

Official Title
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A Multicenter, Randomized, Double-Blind Study Comparing the Efficacy and Safety of Ixekizumab Versus Placebo in Patients With Moderate-to-Severe Genital Psoriasis

Conditions
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Genital Psoriasis, 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: Have chronic plaque psoriasis based on a diagnosis of chronic plaque psoriasis for at least 6 months before baseline. Have moderate-to-severe psoriasis in the genital area at screening and baseline. Have plaque psoriasis in a nongenital area at screening and baseline. Have failed to respond to, or are intolerant of, at least 1 topical therapy used for treatment of psoriasis affecting the genital area. Must agree to use reliable method of birth control, which could include abstinence, during the study and for at least 12 weeks following the last dose of study drug. Exclusion Criteria: Pustular, erythrodermic, and/or guttate forms of psoriasis. History of drug-induced psoriasis. Have recently received certain treatments for psoriasis (in particular, within the past 4 weeks but the restriction can go up to 12 months for some treatments). Have ever received treatment with ixekizumab, secukinumab, brodalumab, or another drug with a similar mode of action. Cannot avoid excessive sun exposure or use of tanning booths for at least 4 weeks prior to baseline and during the study. Are currently enrolled in any other clinical trial involving an investigational product. Serious disorder or illness other than plaque psoriasis. Active or history of malignant disease within 5 years prior to baseline. Serious infection within the last 3 months. Have received a live vaccine within 3 months of baseline or plan to do so during the study. Have received a vaccination with Bacillus Calmette-Guérin (BCG) within the past year. Pregnant or breastfeeding (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: Ixekizumab<br>Blinded Treatment Period: 160 milligrams (mg) ixekizumab given subcutaneously (SC) at baseline followed by 80 mg ixekizumab every 2 weeks (Q2W) SC from week 2 to week 10. At week 12, 80 mg ixekizumab and placebo given SC. Open Label Period: 80 mg ixekizumab given SC every 4 weeks (Q4W) with an option for Q2W dosing starting at week 24, week 28 or week 40. | Drug: Ixekizumab<br>* Administered SC<br>* Other names: LY2439821;Drug: Placebo<br>* Administered SC<br>|
| Placebo Comparator: Placebo<br>Blinded Treatment Period: Placebo given SC at baseline followed by placebo given SC Q2W from week 2 to week 10. At week 12, 160 mg ixekizumab given SC. Open Label Period: 80 mg ixekizumab given SC Q4W with an option for Q2W dosing starting at week 24, week 28 or week 40. | Drug: Ixekizumab<br>* Administered SC<br>* Other names: LY2439821;Drug: Placebo<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Achieving Static Physician Global Assessment (sPGA) of Genitalia (0,1) | sPGA of Genitalia score is based on a combination of erythema and the secondary features (plaque elevation and/or scale). For the analysis of responses, the participant's psoriasis was assessed as follows: 0 = clear,1 = minimal, 2 = mild, 3 = moderate, 4 = severe, 5 = very severe. sPGA of Genitalia (0,1) : A sPGA of Genitalia assessed as either 0 or 1. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Achieving Overall sPGA (0,1) | The overall sPGA is the physician's global assessment of the participant's psoriasis (Ps) lesions at a given time point. Plaques were assessed for induration, erythema, and scaling, and an overall rating of psoriasis severity was given using the anchors of 0 = clear, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe, 5 = very severe. Overall sPGA (0,1) : An overall sPGA assessed as either 0 or 1. | Week 12 | 
| Number of Participants With at Least a 3 Point Improvement in Genital Psoriasis Itch Numeric Rating Scale (NRS) Item Within the Genital Psoriasis Symptom Scale (GPSS) | GPSS is a participant-administered assessment of 8 symptoms: itch, pain, discomfort, stinging, burning, redness, scaling, and cracking. Each respondent was asked to answer the questions based on the psoriasis symptoms in his or her genital area. The overall severity for each individual genital psoriasis symptom is indicated by selecting the number from an Numeric Rating Scale (NRS) of 0 to 10 that best describes the worst level of each symptom in the genital area in the past 24 hours, where 0 (= no severity) and 10 (worst imaginable severity). | Week 12 | 
| Number of Participants Whose Frequency of Sexual Activity is Never or Rarely Limited by Genital Psoriasis, Utilizing the Genital Psoriasis Sexual Frequency Questionnaire (SFQ) Item 2 | The SFQ is a participant reported outcome measure to evaluate the impact of genital psoriasis symptoms on sexual frequency. It consists of 2 items that assess the impact of genital psoriasis symptoms on the frequency of sexual activity. Respondents were asked to answer the questions based on their psoriasis symptoms in the genital area. Item 2 assesses how often genital psoriasis symptoms limited the frequency of sexual activity with the following response options: 0 = never, 1 = rarely, 2 = sometimes, 3 = often, 4 = always. *The SFQ is also referred to as the GenPs-SFQ (genital psoriasis sexual frequency questionnaire). | Week 12 | 
| Number of Participants Whose Frequency of Avoiding Sexual Activity is Either Never or Rarely Limited by Genital Psoriasis in the Sexual Activity Avoidance Subscale Score of the Genital Psoriasis Sexual Impact Scale (GPSIS) | GPSIS is a participant reported outcome measure to evaluate the impact of genital psoriasis symptoms on sexual activity. The GPSIS Sexual Activity Avoidance Subscale includes 2 items: Item 1 asks whether the participant has been sexually active in the past week. (No due to other reasons = 1, No due to genital Ps = 5) Item 2 asks how often the participant avoided sexual activity in the past week due to Genital Psoriasis. (Never = 1, rarely = 2, Sometimes = 3, Often = 4) | Week 12 | 
| Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score | DLQI is a simple, participant-administered, 10 question, validated, quality-of-life questionnaire that covers 6 domains: 1) Symptoms and feelings 2) Daily activities 3) Leisure 4) Work and school 5) Personal relationships 6) Treatment. Response categories include: 0 = not at all; 1 = a little; 2 = a lot; 3 = very much; not relevant responses scored as 0 and total score range of 0 to 30; higher scores indicate poor quality of life. Least Square (LS) Mean was calculated using Mixed Model Repeated Measures (MMRM) model with treatment, baseline body surface area (BSA) category, baseline value, visit, treatment-by-visit, and baseline value-by-visit interactions as fixed effects. | Baseline, Week 12 | 
| Change From Baseline in Modified Genital Psoriasis Area and Severity Index (mGPASI) Score | mGPASI determines participants psoriasis severity in the genital region at a given time point yielding an overall score of 0 for no psoriasis to 72 for the most severe disease. scoring index incorporates the degree of erythema (or redness), induration (or thickness), and scaling) of the genital plaques as well as erosion, fissure, and/or ulcer as a product of the genital area involved. LS Mean was calculated using MMRM model with treatment, baseline BSA category, baseline value, visit, treatment-by-visit, and baseline value-by-visit interactions as fixed effects. | Baseline, Week 12 | 
| Number of Participants With at Least a 2-Point Change in Patient's Global Assessment of Genital Psoriasis (PatGA-Genital) | Patient's Global Assessment of Genital Psoriasis (PatGA-Genital) is a participant-administered, single-item scale on which participants are asked to rank the severity of their genital psoriasis today by circling a number on a 0 to 5 NRS, as follows: from 0 (clear), no genital psoriasis; to 5 (severe). | Week 12 | 
| Change From Baseline on the Short-Form Health Survey (SF-36) Physical Component Summary (PCS) | SF-36 is a participant-reported outcome measure evaluating a 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. Least Squares Mean (LS Mean) was calculated using Analysis of covariance (ANCOVA) model with treatment, baseline BSA category, & baseline value and modified baseline observation carried forward (mBOCF) imputation method. | Baseline, Week 12 | 
| Change From Baseline on the Short-Form Health Survey (SF-36) Mental Component Summary (MCS) | SF-36 is a participant-reported outcome measure evaluating a 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 MCS. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. Least Squares Mean (LS Mean) was calculated using Analysis of covariance (ANCOVA) model with treatment, baseline BSA category, & baseline value and modified baseline observation carried forward (mBOCF) imputation method. | Baseline, Week 12 | 
| Change From Baseline in Genital Psoriasis Symptom Scale (GPSS) Total Score and Individual Items | GPSS is a participant's-administered assessment of 8 symptoms: itch, pain, discomfort, stinging, burning, redness, scaling, and cracking. Each respondent was asked to answer the questions based on the psoriasis symptoms in his or her genital area. The overall severity for each individual genital psoriasis symptom is indicated by selecting the number from an Numeric Rating Scale (NRS) of 0 to 10 that best describes the worst level of each symptom in the genital area in the past 24 hours, where 0 (no severity) and 10 (worst imaginable severity). total score ranges from 0 (no severity) - 80 (worst imaginable severity) LS Mean was calculated using MMRM model with treatment, baseline BSA category, baseline value, visit, treatment-by-visit, and baseline value-by-visit interactions as fixed effects. | Baseline, Week 12 | 
| Number of Participants Achieving sPGA of Genitalia (0,1) at Week 12 by Treatment-Emergent Anti-Drug Antibody (TE-ADA) Status and by Neutralizing Antibody (NAb) Status | sPGA of Genitalia score is based on a combination of erythema and the secondary features (plaque elevation and/or scale). For the analysis of responses, the participant's psoriasis was assessed as follows: 0 = clear,1 = minimal, 2 = mild, 3 = moderate, 4 = severe, 5 = very severe. sPGA of Genitalia (0,1) : A sPGA of Genitalia assessed as either 0 or 1. | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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genital