Evaluation of Ixekizumab Using Auto-Injector or Prefilled Syringe in 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 evaluate the serum concentration of ixekizumab after administration using either prefilled syringe or auto-injector in participants with moderate to severe plaque psoriasis. Treatment period is followed by 40 weeks optional safety extension.

Official Title
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Pharmacokinetic Evaluations of Ixekizumab Following Subcutaneous Administration Using Prefilled Syringe or Auto-Injector in Patients With Moderate-to-Severe Plaque Psoriasis

Conditions
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Plaque Psoriasis

Intervention / Treatment
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* Drug: Ixekizumab Auto-Injector
* Drug: Ixekizumab Prefilled Syringe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Present with chronic plaque psoriasis based on a confirmed diagnosis of chronic psoriasis vulgaris for at least 6 months prior to randomization At least 10% Body Surface Area (BSA) of Psoriasis at screening and at randomization Static Physician Global Assessment (sPGA) score of at least 3 AND Psoriasis Area and Severity Index (PASI) score of at least 12 at screening and at randomization Candidate for phototherapy and/or systemic therapy Men must agree to use a reliable method of birth control during the study Women must agree to use birth control or remain abstinent during the study and for at least 12 weeks after stopping treatment Exclusion Criteria: Pustular, erythrodermic, and/or guttate forms of psoriasis History of drug-induced psoriasis Clinically significant flare of psoriasis during the 12 weeks prior to randomization Concurrent or recent use of any biologic agent Received systemic psoriasis therapy [such as psoralen and ultraviolet A (PUVA) light therapy] or phototherapy within the previous 4 weeks; or had topical psoriasis treatment within the previous 2 weeks prior to randomization Cannot avoid excessive sun exposure or use of tanning booths for at least 4 weeks prior to randomization and during the study Have participated in any study with interleukin-17 (IL-17) antagonists, including Ixekizumab Serious disorder or illness other than plaque psoriasis Serious infection within the last 3 months 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 80 mg Ixekizumab Auto-Injector<br>Ixekizumab administered by two 80 milligram (mg) subcutaneous (SC) injections at Week 0, then one 80 mg SC injection every 2 weeks (Q2W) at week 2, 4, 6, 8 and 10. Starting from Week 12, 80 mg Ixekizumab Prefilled Syringe was administered by one 80 mg SC injection every 4 weeks (Q4W). | Drug: Ixekizumab Auto-Injector<br>* Administered SC by auto-injector<br>* Other names: LY2439821;|
| Experimental: 80 mg Ixekizumab Prefilled Syringe<br>Ixekizumab administered by two 80 mg SC injections at Week 0, then one 80 mg SC injection Q2W at week 2, 4, 6, 8 and 10. Starting from Week 12, 80 mg Ixekizumab Prefilled Syringe was administered by one 80 mg SC injection Q4W. | Drug: Ixekizumab Prefilled Syringe<br>* Administered SC by prefilled syringe<br>* Other names: LY2439821;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) by Drug Delivery Device | Cmax by drug delivery device (prefilled syringe or auto-injector) of Ixekizumab, after the 160 mg starting dose was administered on Day 0. | Day 2, Day 4, Day 7, Day 10 and Day 14 (prior to Ixekizumab administration) | 
| PK: Area Under the Concentration Time Curve From Time Zero to Last Measured Concentration Value (AUC 0-[Tlast]) by Drug Delivery Device | AUC 0-tlast by drug delivery device (prefilled syringe or auto-injector) of Ixekizumab, after the 160 mg starting dose was administered on Day 0. AUC 0-tlast is equal to AUC 0-14 days where the last time point was 14 days ± 24 hours. | Day 2, Day 4, Day 7, Day 10 and Day 14 (prior to Ixekizumab administration) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK: Cmax of Ixekizumab by Site of Injection (Arm, Thigh or Abdomen) | Cmax by site of injection of Ixekizumab, after the 160 mg starting dose was administered on Day 0. | Day 2, Day 4, Day 7, Day 10 and Day 14 (prior to Ixekizumab administration) | 
| PK: AUC 0-tlast by Site of Injection (Arm, Thigh or Abdomen) | AUC 0-tlast by site of injection of Ixekizumab, after the 160 mg starting dose was administered on Day 0. AUC 0-tlast is equal to AUC 0-14 days where the last time point was 14 days ± 24 hours. | Day 2, Day 4, Day 7, Day 10 and Day 14 (prior to Ixekizumab administration) | 
| PK: Cmax by Body Weight | Cmax by body weight of Ixekizumab, after the 160 mg starting dose was administered on Day 0. Body weight is defined by (Low: <80 kilogram (kg), Medium: 80-100 kg, or High: >100 kg). | Day 2, Day 4, Day 7, Day 10 and Day 14 (prior to Ixekizumab administration) | 
| PK: AUC 0-tlast by Body Weight | AUC 0-tlast by body weight of Ixekizumab, after the 160 mg starting dose was administered on Day 0. AUC 0-tlast is equal to AUC 0-14 days where the last time point was 14 days ± 24 hours. Body weight is defined by (Low: <80 kg, Medium: 80-100 kg, or High: >100 kg). | Day 2, Day 4, Day 7, Day 10 and Day 14 (prior to Ixekizumab administration) | 
| Percentage of Participants Achieving a ≥75%, ≥ 90% and 100% Improvement in Psoriasis Area and Severity Index (PASI): Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Psoriasis. Measure: Psoriasis Area and Severity Index (PASI) | PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation, erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 or no Ps to 72 for the most severe disease. Participants achieving PASI 75, 90, or 100 are defined as having an improvement of at least 75%, 90%, or of 100%, respectively, in the PASI scores compared to baseline. | Week 12 | 
| Percentage of Participants With a Static Physician Global Assessment (sPGA) (0,1): Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Psoriasis. Measure: Static Physician Global Assessment (sPGA) | 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. | Week 12 | 
| Percentage of Participants With a Static Physician Global Assessment (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). | Week 12 | 
| Percentage of Device Operation Failures | Device operation failure (that is, incomplete dose administration) was defined as an event during the treatment period (week 0 to week 12) when the participant indicated that a complete dose of ixekizumab was not delivered and/or the drug delivery device did not perform as expected per the directions for use. | Baseline through Week 12 | 
| Percentage of Participants With Anti-Ixekizumab Antibodies | The percentage of participants with treatment-emergent positive anti-ixekizumab antibodies at anytime post-baseline were summarized by drug delivery device group. 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 to Week 12 | 
| SQAAQ Item Scores: Quality of Life and Outcome Assessments. Measures: Patient Reported Outcomes (PRO) | The SQAAQ is a self-administered questionnaire which provides an assessment of ease of use and confidence with using a device to administer a subcutaneous injection of drug. Participants and injection assistants responded to questionnaire items using a 7-point Likert scale (from Strongly Disagree to Strongly Agree). 1 represents Strongly Disagree while 7 represents Strongly Agree. The ease of use and confidence of ixekizumab subcutaneous administrations across drug delivery device groups were evaluated by SQAAQ item scores at each post baseline visit. | Baseline, Week 4 and Week 8 |