A Study in Participants With Moderate to Severe Psoriasis

• ClinicalTrials.gov Identifier: NCT01107457
• Recruitment Status: Completed
• First Posted: April 21, 2010
• Results First Posted: July 25, 2017
• Last Update Posted: September 24, 2019
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

The primary purpose for this study is to help answer the following research questions

• The safety of ixekizumab (LY2439821) and any side effects that might be associated with it.
• Whether ixekizumab can help participants with Psoriasis.
• How much ixekizumab should be given to participants.

Condition or disease	Intervention/treatment	Phase
Psoriasis	Biological: Ixekizumab; Drug: Placebo	Phase 2

Detailed Description:

The study is a Phase 2 study with 3 parts. Part A is a randomized, double-blind, placebo-controlled, parallel-group, dose-ranging design, Part B is an optional, open label extension design and Part C is an additional optional extension period with an open-label design(up to approximately 104 weeks). Approximately 125 participants will be randomized to 1 of 4 ixekizumab groups or to placebo (approximately 25 participants per group) in Part A. Participants will be evaluated for treatment efficacy and the primary endpoint will be evaluated at week 12. Between week 20 and week 32, participants with a less than 75% improvement in their Psoriasis Area and Severity Index (PASI) score compared to baseline will be eligible to begin Part B. Participants in Part B will receive subcutaneous (SC) injections of ixekizumab 120 milligrams (mg) every 4 weeks through week 236. Subsequent to an amendment on May 2012, administration changed to 80 mg every 4 weeks through Week 236. Participants in Part C may receive SC injections of ixekizumab 80 mg every 4 weeks for up to an additional 104 weeks through approximately week 340. Participants who complete Part A, Part B, and Part C will have a total study participation of approximately 344 weeks.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 142 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Dose-Ranging And Efficacy Study of LY2439821 (An Anti-IL-17 Antibody) In Patients With Moderate-To-Severe Psoriasis
• Study Start Date: April 2010
• Actual Primary Completion Date: January 2011
• Actual Study Completion Date: July 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: 10 mg Ixekizumab; Part A: 10 milligrams (mg) ixekizumab given subcutaneous (SC) on weeks 0, 2, 4, 8, 12 and 16 for a total of six administrations. Part B: (optional) 120 mg ixekizumab given SC Q4W. Subsequent to an amendment on May 2012, administration changed to 80 mg Q4W through Week 236. Part C: (optional) 80 mg ixekizumab given SC Q4W through approximately week 344.	Biological: Ixekizumab; Administered subcutaneously; Other Name: LY2439821
Experimental: 25 mg Ixekizumab; Part A: 25 mg ixekizumab given SC on weeks 0, 2, 4, 8, 12 and 16 for a total of six administrations. Part B: (optional) 120 mg ixekizumab given SC (Q4W). Subsequent to an amendment on May 2012, administration changed to 80 mg Q4W through Week 236. Part C: (optional) 80 mg ixekizumab given SC Q4W through approximately week 344.	Biological: Ixekizumab; Administered subcutaneously; Other Name: LY2439821
Experimental: 75 mg Ixekizumab; Part A: 75 mg ixekizumab given SC on weeks 0, 2, 4, 8, 12 and 16 for a total of six administrations. Part B: (optional) 120 mg ixekizumab given SC Q4W. Subsequent to an amendment on May 2012, administration changed to 80 mg Q4W through Week 236. Part C: (optional) 80 mg ixekizumab given SC Q4W through approximately week 344.	Biological: Ixekizumab; Administered subcutaneously; Other Name: LY2439821
Experimental: 150 mg Ixekizumab; Part A: 150 mg ixekizumab given SC on weeks 0, 2, 4, 8, 12 and 16 for a total of six administrations. Part B: (optional) Administered 120 mg ixekizumab SC Q4W. Subsequent to an amendment on May 2012, administration changed to 80 mg Q4W through Week 236. Part C: (optional) 80 mg ixekizumab given SC Q4W through approximately week 344.	Biological: Ixekizumab; Administered subcutaneously; Other Name: LY2439821
Placebo Comparator: Placebo; Part A: Placebo given on weeks 0, 2, 4, 8, 12 and 16 for a total of six administrations. Part B: (optional) 120 mg ixekizumab given SC Q4W. Subsequent to an amendment on May 2012, administration changed to 80 mg Q4W through Week 236. Part C: (optional) 80 mg ixekizumab given SC Q4W through approximately week 344.	Biological: Ixekizumab; Administered subcutaneously; Other Name: LY2439821; Drug: Placebo; Administered subcutaneously
Experimental: 120 mg Ixekizumab; Part B: (optional) 120 mg ixekizumab given SC every 4 weeks. Subsequent to an amendment on May 2012, administration changed to 80 mg every 4 weeks through Week 236. Part C: (optional) 80 mg ixekizumab given SC every 4 weeks through approximately week 344.	Biological: Ixekizumab; Administered subcutaneously; Other Name: LY2439821
Experimental: 80 mg Ixekizumab; Part B: (optional) Subsequent to an amendment on May 2012, administration changed to 80 mg ixekizumab Q4W through Week 236. Part C: (optional) 80 mg ixekizumab given SC every 4 weeks through approximately week 344.	Biological: Ixekizumab; Administered subcutaneously; Other Name: LY2439821

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants Achieving Psoriasis Area and Severity Index ≥75% (PASI 75) Improvement [ Time Frame: Week 12 ]
   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 (none) to 4 (very severe). 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 psoriasis) to 72 (the most severe disease).Participants achieving PASI 75 were defined as having an improvement of ≥75% in the PASI score compared to baseline.
2. Percentage of PASI Improvement From Baseline to 12 Week Endpoint [ Time Frame: Baseline to Week 12 ]
   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 (none) to 4 (very severe). 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 psoriasis) to 72 (the most severe disease). Least squares (LS) mean values were calculated using mixed model repeated measures (MMRM) and controlled for baseline as a covariate, visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured.

Secondary Outcome Measures :

1. Percentage of Participants With a Static Physician's Global Assessment (sPGA) Score of Cleared (0) or Minimal (1) With at Least a 2 Point Improvement" at Week 12 [ Time Frame: Week 12 ]
   The sPGA of psoriasis is scored on a 6-point scale, reflecting a global consideration of the erythema, induration, and scaling across all psoriatic lesions. Average erythema, induration, and scaling are scored separately over the whole body according to a 6 point severity scale (0 [clear] to 5 [severe]). The total score was calculated as average of the 3 severity scores and rounded to the nearest whole number score to determine the sPGA score and category (0=clear; 1=minimal; 2=mild; 3=moderate; 4=marked; 5 = severe). As defined by protocol, a responder is a participant who has a post-baseline sPGA score of '0' or a post-baseline score of '1' with at least a 2 point improvement from baseline.
2. Number of Participants With Treatment Emergent Adverse Events Up to 20 Weeks [ Time Frame: Baseline Up to 20 Weeks ]
   Treatment-emergent adverse events (TEAEs) are events which were not present at baseline or pre-existing conditions at baseline that worsened in severity following the start of treatment. A summary of other non-serious Adverse Events (AEs), and all Serious Adverse Events (SAE's), regardless of causality, is located in the Reported Adverse Events section.
3. Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 16 [ Time Frame: Baseline, Week 16 ]
   The HADS is a 14-item, participant self-reported scale that consists of an anxiety scale and a depression scale, each with 7 items. Items are rated on a 4-point Likert-type scale ranging from 0 (low level of anxiety or depression) to 3 (high level of anxiety or depression). Each subscale score ranges from 0 to 21 with higher scores indicating greater symptom severity. The classification is defined: 0-7 normal, 8-10 Borderline, 11-21 Abnormal. LS mean was calculated using the analysis of covariance (ANCOVA) model including treatment as fixed effect and baseline as covariate.
4. Change From Baseline in 16-Item Quick Inventory of Depressive Symptoms- Self Rated (QIDS-SR16) Total Score at Week 16 [ Time Frame: Baseline, Week 16 ]
   The QIDS-SR16 is a self-administered, 16-item instrument in which a participant is asked to consider each statement as it relates to the way they have felt for the past 7 days. There is a 4-point scale for each item ranging from 0 (best) to 3 (worst). The 16 items are scored to give 9 individual depression domains (sad mood, concentration, self-criticism, suicidal ideation, interest, energy/fatigue, sleep disturbance [initial, middle and late insomnia or hypersomnia], decrease/increase in appetite/weight, and psychomotor agitation/retardation), which are summed to give a single score ranging from 0 to 27, with higher scores denoting greater symptom severity. The LS Mean (no multiplicity adjustments) are presented for each treatment versus placebo comparison at each visit and use an analysis of covariance (ANCOVA) model including baseline as a covariate and treatment as fixed effect in the model.
5. Change From Baseline in Patient Global Assessment (PatGA) at Week 12 [ Time Frame: Baseline, 12 Weeks ]
   The PatGA is a single-item self-reported instrument asking the participant to rate the severity of their psoriasis "today" by circling a number on the numeric rating scale from 0 (Clear = no psoriasis) to 5 (Severe = the worst their psoriasis has ever been). The LS Mean (no multiplicity adjustments) are presented for each treatment versus placebo comparison at each visit and use an analysis of covariance (ANCOVA) model including baseline as a covariate and treatment as fixed effect in the model.
6. Change From Baseline in Pain Visual Analog Scale (VAS) at Week 12 [ Time Frame: Baseline, Week 12 ]
   The pain VAS is a participant-administered single-item scale designed to measure current joint pain from psoriatic arthritis (PsA) using a 100- millimeter (mm) horizontal VAS. Overall severity of participant's joint pain from PsA is indicated by placing a single mark on the horizontal 100-mm scale from 0mm (no pain) to 100 mm (pain as severe as you can imagine). A mixed effects model for repeated measures analysis was used. Least Squares (LS) Mean values were calculated using MMRM and were controlled for baseline as a covariate, visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured.
7. Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-S) at Week 16 [ Time Frame: Baseline, Week 16 ]
   MOS-S provides a concise assessment of important dimensions of sleep, including initiation, maintenance, respiratory problems, quantity, perceived adequacy, and somnolence during the past 4 weeks. Scoring based on 7 subscales: sleep disturbance, snoring, awakened short of breath or with headache, sleep adequacy, and somnolence (range:0-100,with higher scores for more impairment); sleep quantity (range:0-24), and optimal sleep (yes:1, no:0). Six(6) and 9 item index measures of sleep disturbance were constructed to provide composite scores. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range * 100); total score range: 0 to 100; higher score = higher scores indicate greater problems with the attribute.The LS Mean (no multiplicity adjustments) was calculated using an analysis of covariance (ANCOVA) model including baseline as a covariate and treatment as fixed effect in the model.
8. Number of Participants Who Received Medical Care Measured by Medical Care Resource Utilization (PMRU)) [ Time Frame: Week 16 ]
   The PMRU is a 3-item participant-reported questionnaire on health care resource utilization due to psoriasis for physician/clinic visits, emergency room visits, and inpatient hospital admissions since the last study visit.
9. Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI Q) at Week 16 [ Time Frame: Baseline, Week 16 ]
   The WPAI questionnaire has six questions to assess whether the participant was currently employed (Q1); how many hours from work were missed due to problems associated with psoriasis (Q2) or any other reason (Q3); hours actually worked (Q4); degree that psoriasis affected productivity while working (Q5); and degree that psoriasis affected regular activities (Q6) over the past 7 days. Four separate overall scores were calculated, Absenteeism (work time missed) = (Q2/(Q2+Q4))*100, Presenteeism(impairment at work/reduced on-the-job effectiveness) = (Q5/10) *100, Work productivity loss(overall work impairment /absenteeism plus presenteeism) = (Q2/(Q2+Q4)+[(1-Q2/(Q2+Q4))x(Q5/10)]) * 100 and Activity Impairment = (Q6/10) * 100. Each score ranges from 0 to 100 with higher scores indicating greater impairment and less productivity ( worse outcomes). The LS Mean was calculated using ANCOVA model including baseline as a covariate and treatment as fixed effect in the model.
10. Change From Baseline in Medical Outcomes Study Short-Form 36 (SF-36) - Physical Component Score (PCS) and Mental Component Score (MCS) at Week 16 [ Time Frame: Baseline, Week 16 ]
    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. The 8 domains are regrouped into the PCS and MCS scores. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. The recall period was the past 4 weeks. The LS Mean was calculated using ANCOVA model including baseline as a covariate and treatment as fixed effect in the model.
11. Change From Baseline in Nail Psoriasis Severity Index (NAPSI) in Participants With Nail Psoriasis at Week 12 [ Time Frame: Baseline, Week 12 ]
    The NAPSI is physician-rated and quantifies the severity of nail psoriasis by evaluating the presence or absence of psoriatic manifestations on the nail matrix and nail bed. Each finger nail is divided with imaginary lines into quadrants and scored for both nail matrix and nail bed psoriasis (range from 0 [absence of psoriasis] to 4 [presence of psoriasis in all 4 quadrants]). Participant's fingers and toes were evaluated and the sum of the scores was added resulting in a range of 0 to 160; higher scores indicate greater severity. If an individual toe or finger assessment was missing (not done), the average of the remaining measured digits was imputed and added to the sum. If <50% of the toes or finger assessments were missing, the imputation was performed. If >50% of the assessments were missing, then the sum of the scores was left as missing. LS mean was calculated using MMRM with baseline score as covariate, visit, treatment and visit by treatment interaction as fixed effects.
12. Change From Baseline in Palmoplantar Psoriasis Severity Index (PPASI) in Participants With Palmoplantar Psoriasis at Week 12 [ Time Frame: Baseline, Week 12 ]
    The PPASI is a physician-assessed composite score derived from the summed scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement. The PPASI score ranges from 0 to 72, with higher scores representing greater severity of palmoplantar psoriasis.LS mean was calculated using MMRM with baseline score as covariate, visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to symmetric.
13. Change From Baseline in Scalp Psoriasis Severity Index (PSSI) in Participants With Scalp Psoriasis at Week 12 [ Time Frame: Baseline, Week 12 ]
    The PSSI is a physician-assessed composite score derived from the summed scores for erythema, induration, and desquamation multiplied by a score for the extent of scalp area involved. The PSSI score ranges from 0 to 72, with higher scores representing greater severity of scalp psoriasis.LS mean was calculated using MMRM with baseline score as covariate, visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured.
14. Ixekizumab Systemic Clearance (CL) (Serum Concentrations of Ixekizumab From Baseline Through 32 Weeks) [ Time Frame: Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28 and Week 32 ]
    The population pharmacokinetic (PK) modeling value for systemic clearance was based on data from week 1 to week 32 for all participants in all ixekizumab treatment arms.
15. Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score Total Score at Week 16 [ Time Frame: Baseline, Week 16 ]
    The DLQI is a 10-item, participant-administered dermatology-specific questionnaire that assess health related quality of life that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. The DLQI items response categories are scored 0 (not relevant) to 3 (very much) with a total score range of 0 to 30; higher scores indicate poor quality of life and a 5-point change from baseline is considered clinically relevant. The LS Mean(no multiplicity adjustments) are presented for each treatment versus placebo comparison at each visit and use an analysis of covariance (ANCOVA) model including baseline as a covariate and treatment as fixed effect in the model.
16. Change From Baseline in Psoriasis Area and Severity Index (PASI) Score at Week 12 [ Time Frame: Baseline, Week 12 ]
    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(none) to 4(very severe).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 psoriasis) to 72(most severe disease).The LS mean are presented for each treatment versus placebo comparison at each visit and use ANCOVA model including baseline PASI covariate and treatment as fixed effect in the model.Results at Week 12 are summarized as Improvement in PASI which is defined as a reduction in the PASI calculated score at a visit as compared to the score calculated at the baseline visit.
17. Percentage of Participants Who Achieve a 75% Improvement in the Psoriasis Area and Severity Index (PASI 75) [ Time Frame: Week 32 ]
    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 (none) to 4 (very severe). 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 psoriasis) to 72 (the most severe disease). Participants achieving PASI 75 were defined as having an improvement of ≥75% in the PASI score compared to baseline.
18. Percentage of PASI Improvement From Baseline Through 32 Weeks [ Time Frame: Baseline Through 32 Weeks ]
    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 (none) to 4 (very severe). 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 psoriasis) to 72 (the most severe disease). Improvement in PASI is defined as improvement in the PASI calculated score at a visit as compared to the score calculated at the baseline visit.
19. Percentage of Participants With a Static Physician's Global Assessment (sPGA) Score of Cleared (0) or Minimal (1) With at Least a 2 Point Improvement [ Time Frame: Week 32 ]
    The sPGA of psoriasis is scored on a 6-point scale, reflecting a global consideration of the erythema, induration, and scaling across all psoriatic lesions. Average erythema, induration, and scaling are scored separately over the whole body according to a 6-point severity scale (0 [clear] to 5 [severe]). The total score was calculated as average of the 3 severity scores and rounded to the nearest whole number score to determine the sPGA score and category (0=clear; 1=minimal; 2=mild; 3=moderate; 4=marked; 5 = severe). As defined by protocol, a responder is a participant who has a post-baseline sPGA score of '0' or a post-baseline score of '1' with at least a 2 point improvement from baseline.
20. Percentage of Participants With Anti-Ixekizumab Antibodies [ Time Frame: Baseline through Week 20 ]
    Percentage of participants with treatment-emergent positive anti-ixekizumab antibodies was summarized by treatment 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%.
21. Percentage of Participants With Static Physician's Global Assessment (sPGA) of (0,1) [ Time Frame: Baseline Up to 240 Weeks ]
    The sPGA of psoriasis is scored on a 6-point scale, reflecting a global consideration of the erythema, induration, and scaling across all psoriatic lesions. Average erythema, induration, and scaling are scored separately over the whole body according to a 6-point severity scale (0 [clear] to 5 [severe]). The total score was calculated as average of the 3 severity scores and rounded to the nearest whole number score to determine the sPGA score and category (0=clear; 1=minimal; 2=mild; 3=moderate; 4=marked; 5 = severe). As defined by protocol, a responder is a participant who has a post-baseline sPGA score of '0' or a post-baseline score of '1' with at least a 2 point improvement from baseline.
22. Number of Treatment Emergent Adverse Events up to 344 Weeks [ Time Frame: Baseline Up to 344 Weeks ]
    Treatment-emergent adverse events (TEAEs) are events which were not present at baseline or pre-existing conditions at baseline that worsened in severity following the start of treatment. A summary of other non-serious Adverse Events (AEs), and all Serious Adverse Events (SAE's), regardless of causality, is located in the Reported Adverse Events section.
23. Change From Baseline in Hospital Anxiety and Depression Scale (HADS) [ Time Frame: Baseline Up to 240 Weeks ]
    The HADS is a 14-item, participant self-reported scale that consists of an anxiety scale and a depression scale, each with 7 items. Items are rated on a 4-point Likert-type scale ranging from 0 (low level of anxiety or depression) to 3 (high level of anxiety or depression). Each subscale score ranges from 0 to 21 with higher scores indicating greater symptom severity. The classification is defined: 0-7 normal, 8-10 Borderline, 11-21 Abnormal.
24. Number of Participants With Patient's Global Assessment of Disease Activity (PatGA) [ Time Frame: Week 240 ]
    The PatGA is a single-item self-reported instrument asking the participant to rate the severity of their psoriasis "today" by circling a number on the numeric rating scale from 0 (Clear = no psoriasis) to 5 (Severe = the worst their psoriasis has ever been).
25. Change From Baseline in Pain Visual Analog Scale (VAS) [ Time Frame: Baseline Up to 240 Weeks ]
    The pain VAS is a participant-administered single-item scale designed to measure current joint pain from psoriatic arthritis (PsA) using a 100- millimeter (mm) horizontal VAS. Overall severity of participant's joint pain from PsA is indicated by placing a single mark on the horizontal 100-mm scale from 0mm (no pain) to 100 mm (pain as severe as you can imagine). A mixed effects model for repeated measures analysis was used.
26. Change From Baseline up to 240 Weeks in Nail Psoriasis Severity Index (NAPSI) in Participants With Nail Psoriasis [ Time Frame: Baseline Up to 240 Weeks ]

    The NAPSI is physician-rated and quantifies the severity of nail psoriasis by evaluating the presence or absence of psoriatic manifestations on the nail matrix and nail bed. Each finger nail is divided with imaginary lines into quadrants and scored for both nail matrix and nail bed psoriasis (range from 0 [absence of psoriasis] to 4 [presence of psoriasis in all 4 quadrants]). Participant's fingers and toes were evaluated and the sum of the scores was added resulting in a range of 0 to 160; higher scores indicate greater severity. If an individual toe or finger assessment was missing (not done), the average of the remaining measured digits was imputed and added to the sum. If <50% of the toes or finger assessments were missing, the imputation was performed. If >50% of the assessments were missing, then the sum of the scores was left as missing.

    Baseline is defined as the last available value prior to the first dose in Part A of the study.

27. Change From Baseline up to 240 Weeks in Scalp Psoriasis Severity Index (PSSI) in Participants With Scalp Psoriasis [ Time Frame: Baseline Up to 240 Weeks ]

    The PSSI is a physician-assessed composite score derived from the summed scores for erythema, induration, and desquamation multiplied by a score for the extent of scalp area involved. The PSSI score ranges from 0 to 72, with higher scores representing greater severity of scalp psoriasis.

    Baseline is defined as the last available value prior to the first dose in Part A of the study.

28. Change From Baseline up to 240 Weeks in Palmoplantar Psoriasis Severity Index (PPASI) in Participants With Palmoplantar Psoriasis [ Time Frame: Baseline Up to 240 Weeks ]
    The PPASI is a physician-assessed composite score derived from the summed scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement. The PPASI score ranges from 0 to 72, with higher scores representing greater severity of palmoplantar psoriasis.LS mean was calculated using MMRM with baseline score as covariate, visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to symmetric.
29. Percentage of Participants Achieving Psoriasis Area and Severity Index ≥75% (PASI 75) Improvement [ Time Frame: Week 240 ]
    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 (none) to 4 (very severe). 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 psoriasis) to 72 (the most severe disease).Participants achieving PASI 75 were defined as having an improvement of ≥75% in the PASI score compared to baseline.
30. Change From Baseline in Dermatology Life Quality Index (DLQI) [ Time Frame: Baseline Up to 240 Weeks ]

    The DLQI is a 10-item, participant-administered dermatology-specific questionnaire that assess health related quality of life that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. The DLQI items response categories are scored 0 (not relevant) to 3 (very much) with a total score range of 0 to 30; higher scores indicate poor quality of life and a 5-point change from baseline is considered clinically relevant.

    Baseline is defined as the last available value prior to the first dose in Part A of the study.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria Common to Both Part A:

• Participant must have active plaque psoriasis covering at least 10% body surface area and a PASI score of at least 12 at screening and at randomization.
• Participant is a candidate for systemic therapy
• Participant has a Static Physician's Global Assessment (sPGA) score of at least 3 at screening and at randomization

Inclusion Criterion Specific to Part B

• Participant has completed the treatment period for part A (at least through week 20)

Inclusion Criterion Specific to Part C

• Participant has completed the treatment period for part B

Exclusion Criteria Common to Part A, B and C:

• Participant has pustular, erythrodermic and/or guttate forms of psoriasis
• Participant has had a clinically significant flare of psoriasis during the 12 weeks prior to study entry
• Participant has recently used any biologic agent/monoclonal antibody within the following washout periods: etanercept >28 days, infliximab or adalimumab >56 days, alefacept >60 days, ustekinumab >8 months, or any other biologic agent/monoclonal antibody >5 half-lives prior to baseline
• Participant has received systemic psoriasis therapy (such as psoralen and ultraviolet A [PUVA] light therapy, cyclosporine, corticosteroids, methotrexate, oral retinoids, mycophenolate mofetil, thioguanine, hydroxyurea, sirolimus, azathioprine) or phototherapy (including ultraviolet B or self-treatment with tanning beds) within the previous 4 weeks; or had topical psoriasis treatment within the previous 2 weeks prior to randomization (exception: class 6 [mild, such as desonide] or 7 [least potent, such as hydrocortisone] topical steroids will be permitted for use limited to the face, axilla, and/or genitalia)
• Participant has donated more than 500 mL of blood within the last month
• Participant has another serious disorder or illness
• Participant has suffered a serious bacterial infection (for example, pneumonia, and cellulitis) within the last 3 months
• Participant has a history of uncontrolled high blood pressure
• Participant has clinical laboratory test results at entry that are outside the normal reference range
• Participant is currently participating in or were discontinued within the last 30 days from another clinical trial involving an investigational drug
• Participant is a woman who is lactating or breast feeding
• If a participant is a woman and could become pregnant during this study, she must talk to the study doctor about the birth control that you will use to avoid getting pregnant during the study
• If a participant is post menopausal woman, she must be at least 45 years of age and have not menstruated for the last 12 months
• If a participant is a woman between 40-45 years of age, test negative for pregnancy, and have not menstruated during the last 12 months only, she must have an additional blood test to see if you can participate
• If the participant is male, he must agree to reduce the risk of female partner becoming pregnant during the study

Exclusion Criteria Specific to B:

• If a participant experienced a serious adverse event during Part A considered possibly related to ixekizumab
• If a participant experienced an adverse event during Part A that the study doctor believes continued ixekizumab treatment could cause harm to the participant.

Exclusion Criteria Specific to C:

• If a participant experienced a Serious Adverse Event during Part B considered possibly related to ixekizumab
• If a participant experienced an adverse event during Part B that the study doctor believes continued ixekizumab treatment could cause harm to the participant.

Contacts and Locations

Locations

United States, California

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Bakersfield, California, United States, 93309

United States, Connecticut

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New Haven, Connecticut, United States, 06511

United States, District of Columbia

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Washington, District of Columbia, United States, 20037

United States, Florida

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Miami, Florida, United States, 33175

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Miramar, Florida, United States, 33027

United States, Georgia

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Newnan, Georgia, United States, 30263

United States, Illinois

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Arlington Heights, Illinois, United States, 60005

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Skokie, Illinois, United States

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West Dundee, Illinois, United States, 60118

United States, Indiana

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South Bend, Indiana, United States, 46617

United States, Massachusetts

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Boston, Massachusetts, United States, 02114

United States, Michigan

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Ann Arbor, Michigan, United States, 48109

United States, Missouri

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Saint Louis, Missouri, United States, 63117

United States, Nebraska

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Omaha, Nebraska, United States, 68144

United States, Nevada

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Reno, Nevada, United States, 89511

United States, New York

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Jamaica, New York, United States, 11418

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New York, New York, United States, 10029

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Rochester, New York, United States, 14623

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Stony Brook, New York, United States, 11790

United States, North Carolina

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Winston-Salem, North Carolina, United States, 27103

United States, Ohio

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Cleveland, Ohio, United States, 44106

United States, Oregon

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Lake Oswego, Oregon, United States, 97035

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Portland, Oregon, United States, 97223

United States, Pennsylvania

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Philadelphia, Pennsylvania, United States, 19103

United States, Tennessee

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Knoxville, Tennessee, United States, 37922

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Nashville, Tennessee, United States, 37215

United States, Texas

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College Station, Texas, United States, 77845

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Dallas, Texas, United States, 75246

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San Antonio, Texas, United States, 78229

United States, Virginia

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Norfolk, Virginia, United States, 23507

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Richmond, Virginia, United States, 23294

Denmark

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Aarhus, Denmark, 8000

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Hellerup, Denmark, 2900

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Kobenhavn, Denmark, 2400

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Langley RG, Rich P, Menter A, Krueger G, Goldblum O, Dutronc Y, Zhu B, Wei H, Cameron GS, Heffernan MP. Improvement of scalp and nail lesions with ixekizumab in a phase 2 trial in patients with chronic plaque psoriasis. J Eur Acad Dermatol Venereol. 2015 Sep;29(9):1763-70. doi: 10.1111/jdv.12996. Epub 2015 Feb 18.

Gordon KB, Leonardi CL, Lebwohl M, Blauvelt A, Cameron GS, Braun D, Erickson J, Heffernan M. A 52-week, open-label study of the efficacy and safety of ixekizumab, an anti-interleukin-17A monoclonal antibody, in patients with chronic plaque psoriasis. J Am Acad Dermatol. 2014 Dec;71(6):1176-82. doi: 10.1016/j.jaad.2014.07.048. Epub 2014 Sep 19.

Leonardi C, Matheson R, Zachariae C, Cameron G, Li L, Edson-Heredia E, Braun D, Banerjee S. Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N Engl J Med. 2012 Mar 29;366(13):1190-9. doi: 10.1056/NEJMoa1109997.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01107457
• Other Study ID Numbers: 12060; I1F-MC-RHAJ ( Other Identifier: Eli Lilly and Company )
• First Posted: April 21, 2010
• Results First Posted: July 25, 2017
• Last Update Posted: September 24, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: https://vivli.org/

Keywords provided by Eli Lilly and Company:

Moderate; Severe; Plaque; Chronic

Additional relevant MeSH terms:

Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Ixekizumab; Dermatologic Agents