Psoriasis
Conditions
Brief summary
This study will assess the safety and efficacy of LY2439821 compared to placebo in participants with moderate to severe, chronic plaque psoriasis.
Interventions
DRUG80 mg Ixekizumab Dosing Regimens 1, 2, and 3
Administered SC
DRUGPlacebo
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 (IL)-17 antagonists, including LY2439821 * Serious disorder or illness other than plaque psoriasis * Serious infection within the last 3 months * Breastfeeding or nursing (lactating) women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Static Physician Global Assessment (sPGA) of 0 or 1 (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Ps Measure: sPGA) | Week 12 | 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. Participants Ps were 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. |
| Percentage of Participants Achieving ≥75% Improvement in Ps Area and Severity Index (PASI75) (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Psoriasis Measure: PASI) | 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 (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 achieving PASI75 were defined as having an improvement of ≥75% in the PASI score compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Maintaining sPGA 0 or 1 After Re-Randomization at Start of Maintenance Dosing Period | Week 60 | 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. Participants Ps were assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe). |
| Percentage of Participants With Itch Numeric Rating Scale (Itch NRS) Score ≥4 Point Reduction From Baseline | Baseline, Week 12 | The Itch NRS is a participant-administered, 11-point horizontal scale anchored at 0 (no itch) and 10 (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. |
| Change From Baseline in Dermatology-Specific Quality of Life Index (DLQI) Score | Baseline, Week 12 | DLQI is a participant-administered, 10-question, validated, 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 0 (not at all), 1 (a little), 2 (a lot), and 3 (very much) and unanswered (not relevant) responses were scored as 0. Total scores range from 0 to 30, with higher score indicating greater quality of life is impairment. A 5-point change from baseline is considered clinically relevant. Least squares (LS) mean change from baseline was calculated using mixed model repeated measures (MMRM). |
| Change From Baseline in Nail Psoriasis Severity Index (NAPSI) | Baseline, Week 12 | The NAPSI is a numeric, reproducible, objective tool for evaluation of fingernail Ps. This scale is used to evaluate the severity of fingernail bed Ps and fingernail matrix Ps by area of involvement in the fingernail unit. The fingernail is divided with imaginary horizontal and longitudinal lines into quadrants. Each fingernail is given a score for fingernail bed Ps 0 (none) to 4 (Ps in 4 quadrants of the fingernail) and fingernail matrix Ps 0 (none) to 4 (Ps in 4 quadrants of the matrix), depending on the presence (score of 1) or absence (score of 0) of any of the features of fingernail bed or matrix Ps in each quadrant. The NAPSI score of a fingernail is the sum of scores in fingernail bed and fingernail matrix from each quadrant (maximum of 8). Each fingernail is evaluated, then the sum of all fingernails equals the total NAPSI score with a range from 0 to 80 with higher scores indicating more severe psoriasis. LS mean change from baseline was calculated using MMRM. |
| Percent of Body Surface Area (BSA) Involvement of Ps | Week 12 | BSA is a physician rating of the percentage of involvement of Ps for each participant. BSA is assessed on a continuous scale from 0% (no involvement) to 100% (full involvement), where 1% corresponds to the size of the participants hand (includes the palm, fingers and thumb). Total BSA is the sum of handprints from the affected areas. LS mean change from baseline was calculated using MMRM. |
| Change From Baseline in Psoriasis Scalp Severity Index (PSSI) | Baseline, Week 12 | 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 scores range from 0 to 72, with lower scores indicating less severity. LS mean change from baseline was calculated using MMRM. |
| Percentage of Participants Achieving an sPGA of 0 (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Ps Measure: sPGA) | Week 12 | 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. Participants Ps were assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe). |
| Change From Baseline in Quick Inventory of Depressive Symptomatology-Self Reported 16 Items (QIDS-SR16) | Baseline, Week 12 | QIDS-SR16 is a participant-administered, 16-item instrument intended to assess the existence and severity of symptoms of depression. A participant is asked to consider each statement as it relates to the way they have felt for the past 7 days and rate each on a 4-point scale: 0 (best) to 3 (worst). The sum of the 16 items corresponding to 9 depression domains \[sad mood, concentration, self-criticism, suicidal ideation, interest, energy/fatigue, sleep disturbance (initial, middle and late insomnia or hypersomnia), decrease/increase in appetite/weight, and psychomotor agitation/retardation\] to give a single total scores range from 0 to 27, with higher scores indicating greater symptom severity. LS mean change from baseline was calculated using ANCOVA. |
| Change From Baseline in Medical Outcomes Study 36-item Short Form Health Survey (SF-36) and Physical Component Summary (PCS) and Mental Component Summary (MCS) | Baseline, Week 12 | The SF-36 is a self-reported instrument that measures the participant's health status during the previous 7 days. 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 in the PCS and MCS scores. Scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. LS mean change from baseline was calculated using ANCOVA. |
| Change From Baseline in Patient's Global Assessment of Disease Severity (PatGA) | Baseline, Week 12 | 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). LS mean change from baseline calculated using MMRM. |
| Percentage of Participants Achieving Palmoplantar PASI (PPASI) of ≥50% (PPASI50), ≥75% (PPASI75), or 100% (PPASI100) Improvement | Week 12 | The Palmoplantar PASI is a composite score derived from the sum of scores for erythema, induration, and desquamation \[scores range from 0 (none) to 4 (very severe) for each\] multiplied by the score for the extent of palm and sole area involvement \[scores range from 0 (0%) to 6 (90 to100%)\], with a total scores range from 0 to 72. Participants achieving PPASI50, PPASI75 or PASI100 were defined as having an improvement of at least 50%, 90%, or of 100%, respectively, in the PPASI scores compared to baseline. |
| Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough ss) | Weeks 12: Day 84 and Week 24: Day 168 | — |
| Percentage of Participants With Anti-ixekizumab Antibodies | Baseline through Week 12 | 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%. |
| Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) Quality of Life and Outcome Assessments. Measures: Participant Reported Outcomes (PRO) | Baseline, Week 12 | WPAI-PSO is a participant administered, 6-item instrument used to assess the impact of Ps on the productivity impairment within the past 7 days. WPAI-PSO has 4 domains: absenteeism, presenteeism (reduced productivity while at work), an overall work impairment score, and impairment in daily activities performed outside of work. Four scores are derived as percentages: absenteeism, presenteeism (reduced productivity while at work), overall work impairment (absenteeism and presenteeism), and impairment in activities performed outside of work. Percentage is calculated as: each score \* 100 with greater scores indicating greater impairment. LS mean change from baseline was calculated using analysis of covariance (ANCOVA). |
| Percentage of Participants Achieving PASI 90% (PASI90) or 100% (PASI100) (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Ps Measure: PASI) | 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 (no involvement) to 4 (severe involvement). 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 Ps) to 72 (the most severe disease). Participants achieving PASI90 or PASI100 were defined as having an improvement of ≥90% or of 100% respectively in PASI scores compared to baseline. |
Countries
Australia, Canada, Denmark, Germany, Hungary, Italy, Japan, Poland, Romania, United Kingdom, United States
Participant flow
Recruitment details
Induction Period (Week 0 to 12), Maintenance Period (Week 12 to 60); Long term Extension (Week 60 to 264) and Post treatment ( last treatment visit (week 264), or Early Termination Visit (ETV) up to a minimum of 12 weeks following that visit.
Pre-assignment details
Participants received Ixekizumab (ixe) as responders (Resp, sPGA 0/1) in Induction (IND) re-randomized to receive ixe Q4W, Q12W or placebo (PBO) in Maintenance (MAIN) \[Primary Population (Pop)\]. In MAIN, non-responders (Non-Resp, sPGA \>1) in IND received ixe Q4W, PBO Resp in IND received PBO (Secondary Pop). Ixe or PBO continued to end of study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo administered as 2 SC injections Q2W up to Week 10. | 431 |
| Ixe Q4W 160 mg ixe administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection Q4W. | 432 |
| Ixe Q2W 160 mg ixe administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection Q2W up to Week 10. | 433 |
| Total | 1,296 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Induction Period | Adverse Event | 6 | 10 | 10 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period | Lack of Efficacy | 7 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period | Lost to Follow-up | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period | Protocol Violation | 3 | 6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period | Sponsor Decision | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period | Withdrawal by Subject | 6 | 6 | 5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Long-Term Extension Period | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 57 | 58 | 0 | 0 | 0 | 0 |
| Long-Term Extension Period | Clinical Relapse | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 9 | 9 | 0 | 0 | 0 | 0 |
| Long-Term Extension Period | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 9 | 9 | 0 | 0 | 0 | 0 |
| Long-Term Extension Period | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 24 | 25 | 0 | 0 | 0 | 0 |
| Long-Term Extension Period | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 25 | 25 | 0 | 0 | 0 | 0 |
| Long-Term Extension Period | Parent/Caregiver Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
| Long-Term Extension Period | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 21 | 21 | 0 | 0 | 0 | 0 |
| Long-Term Extension Period | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 5 | 0 | 0 | 0 | 0 |
| Long-Term Extension Period | Sponsor Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 | 6 | 0 | 0 | 0 | 0 |
| Long-Term Extension Period | Switched From PBO to Ixe | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 21 | 0 | 0 | 0 | 0 | 0 | 0 |
| Long-Term Extension Period | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 61 | 61 | 0 | 0 | 0 | 0 |
| Maintenance Period | Adverse Event | 0 | 0 | 0 | 4 | 2 | 7 | 0 | 19 | 1 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Period | Clinical Relapse | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Period | Death | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Period | Lack of Efficacy | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 11 | 11 | 12 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Period | Lost to Follow-up | 0 | 0 | 0 | 3 | 3 | 0 | 0 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Period | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Period | Protocol Violation | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Period | Relapsed (sPGA ≥3) | 0 | 0 | 0 | 186 | 111 | 39 | 9 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Period | Treated but Discontinued in Induction | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Period | Withdrawal by Subject | 0 | 0 | 0 | 6 | 2 | 3 | 1 | 6 | 3 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Post-Treatment Follow-Up | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 8 | 2 | 58 | 11 |
| Post-Treatment Follow-Up | Clinical Relapse | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 | 2 |
| Post-Treatment Follow-Up | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Post-Treatment Follow-Up | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 2 | 31 | 3 |
| Post-Treatment Follow-Up | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 12 | 7 |
| Post-Treatment Follow-Up | Parent/Caregiver Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
| Post-Treatment Follow-Up | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 5 |
| Post-Treatment Follow-Up | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 4 | 0 |
| Post-Treatment Follow-Up | Sponsor Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 4 | 0 |
| Post-Treatment Follow-Up | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 2 | 36 | 17 |
Baseline characteristics
| Characteristic | Placebo | Ixe Q4W | Ixe Q2W | Total |
|---|---|---|---|---|
| Age, Continuous | 46.4 years STANDARD_DEVIATION 13.4 | 45.6 years STANDARD_DEVIATION 12.95 | 45.1 years STANDARD_DEVIATION 12.4 | 45.7 years STANDARD_DEVIATION 12.93 |
| Dermatology-Specific Quality of Life Index (DLQI) Score | 12.8 units on a scale STANDARD_DEVIATION 7.11 | 13.2 units on a scale STANDARD_DEVIATION 7.02 | 13.4 units on a scale STANDARD_DEVIATION 7.02 | 13.1 units on a scale STANDARD_DEVIATION 7.05 |
| Itch Numeric Rating Scale (NRS) | 7.0 units on a scale STANDARD_DEVIATION 2.58 | 7.0 units on a scale STANDARD_DEVIATION 2.5 | 7.2 units on a scale STANDARD_DEVIATION 2.39 | 7.1 units on a scale STANDARD_DEVIATION 2.49 |
| Medical Outcomes Study 36-Item Short Form (SF36) Physical component (PCS) and Mental Component (MCS) MCS | 48.77 units on a scale STANDARD_DEVIATION 11.182 | 47.46 units on a scale STANDARD_DEVIATION 11.655 | 47.94 units on a scale STANDARD_DEVIATION 11.535 | 48.05 units on a scale STANDARD_DEVIATION 11.463 |
| Medical Outcomes Study 36-Item Short Form (SF36) Physical component (PCS) and Mental Component (MCS) PCS | 46.92 units on a scale STANDARD_DEVIATION 9.769 | 47.34 units on a scale STANDARD_DEVIATION 9.169 | 46.58 units on a scale STANDARD_DEVIATION 9.146 | 46.95 units on a scale STANDARD_DEVIATION 9.363 |
| Nail Psoriasis Severity Index (NAPSI) | 26.9 units on a scale STANDARD_DEVIATION 20.492 | 24.12 units on a scale STANDARD_DEVIATION 18.243 | 24.64 units on a scale STANDARD_DEVIATION 18.916 | 24.95 units on a scale STANDARD_DEVIATION 19.238 |
| Patient's Global Assessment of Disease Severity (PatGA) | 4.1 units on a scale STANDARD_DEVIATION 0.95 | 4.1 units on a scale STANDARD_DEVIATION 0.88 | 4.1 units on a scale STANDARD_DEVIATION 0.94 | 4.1 units on a scale STANDARD_DEVIATION 0.92 |
| Percent of Body Surface Area (BSA) involvement of Ps | 27.4 percent of body surface STANDARD_DEVIATION 17.77 | 27.4 percent of body surface STANDARD_DEVIATION 16.2 | 28.2 percent of body surface STANDARD_DEVIATION 17.83 | 27.7 percent of body surface STANDARD_DEVIATION 17.27 |
| Psoriasis Area and Severity Index (PASI) | 20.32 units on a scale STANDARD_DEVIATION 8.641 | 20.03 units on a scale STANDARD_DEVIATION 7.304 | 20.09 units on a scale STANDARD_DEVIATION 7.992 | 20.15 units on a scale STANDARD_DEVIATION 7.992 |
| Psoriasis Scalp Severity Index (PSSI) | 21.8 units on a scale STANDARD_DEVIATION 15.7 | 19.9 units on a scale STANDARD_DEVIATION 14.83 | 21.1 units on a scale STANDARD_DEVIATION 14.69 | 20.9 units on a scale STANDARD_DEVIATION 15.08 |
| Quick Inventory of Depressive Symptomatology-Self Reported 16 Items (QIDS-SR16) | 4.7 units on a scale STANDARD_DEVIATION 4.34 | 5.0 units on a scale STANDARD_DEVIATION 4.34 | 4.5 units on a scale STANDARD_DEVIATION 4.09 | 4.8 units on a scale STANDARD_DEVIATION 4.26 |
| Region of Enrollment Australia | 19 Participants | 15 Participants | 8 Participants | 42 Participants |
| Region of Enrollment Canada | 77 Participants | 69 Participants | 66 Participants | 212 Participants |
| Region of Enrollment Denmark | 4 Participants | 4 Participants | 8 Participants | 16 Participants |
| Region of Enrollment Germany | 88 Participants | 106 Participants | 93 Participants | 287 Participants |
| Region of Enrollment Hungary | 23 Participants | 17 Participants | 26 Participants | 66 Participants |
| Region of Enrollment Italy | 3 Participants | 2 Participants | 1 Participants | 6 Participants |
| Region of Enrollment Japan | 13 Participants | 12 Participants | 8 Participants | 33 Participants |
| Region of Enrollment Poland | 43 Participants | 41 Participants | 55 Participants | 139 Participants |
| Region of Enrollment Romania | 8 Participants | 3 Participants | 2 Participants | 13 Participants |
| Region of Enrollment United Kingdom | 7 Participants | 7 Participants | 7 Participants | 21 Participants |
| Region of Enrollment United States | 146 Participants | 156 Participants | 159 Participants | 461 Participants |
| Sex: Female, Male Female | 128 Participants | 143 Participants | 142 Participants | 413 Participants |
| Sex: Female, Male Male | 303 Participants | 289 Participants | 291 Participants | 883 Participants |
| Static Physician Global Assessment (sPGA) sPGA=3 | 204 Participants | 197 Participants | 231 Participants | 632 Participants |
| Static Physician Global Assessment (sPGA) sPGA=4, 5 | 227 Participants | 235 Participants | 202 Participants | 664 Participants |
| Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) Absenteeism | 4.5 units on a scale STANDARD_DEVIATION 17.07 | 4.0 units on a scale STANDARD_DEVIATION 16.26 | 5.7 units on a scale STANDARD_DEVIATION 19.41 | 4.7 units on a scale STANDARD_DEVIATION 17.63 |
| Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) Activity Impairment | 31.3 units on a scale STANDARD_DEVIATION 29.29 | 34.7 units on a scale STANDARD_DEVIATION 28.83 | 34.2 units on a scale STANDARD_DEVIATION 28.99 | 33.4 units on a scale STANDARD_DEVIATION 29.05 |
| Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) Presenteeism | 22.2 units on a scale STANDARD_DEVIATION 25.85 | 25.2 units on a scale STANDARD_DEVIATION 27.22 | 22.6 units on a scale STANDARD_DEVIATION 26.46 | 23.3 units on a scale STANDARD_DEVIATION 26.53 |
| Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) Work Productively Loss | 24.6 units on a scale STANDARD_DEVIATION 27.9 | 27.0 units on a scale STANDARD_DEVIATION 27.9 | 24.9 units on a scale STANDARD_DEVIATION 28.77 | 25.5 units on a scale STANDARD_DEVIATION 28.18 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 128 / 431 | 159 / 432 | 170 / 433 | 83 / 226 | 122 / 227 | 115 / 229 | 8 / 16 | 211 / 391 | 55 / 78 | 34 / 62 | 114 / 348 | 8 / 26 | 414 / 1,054 | 414 / 1,075 | 3 / 18 | 2 / 25 | 33 / 700 | 15 / 285 |
| serious Total, serious adverse events | 5 / 431 | 12 / 432 | 7 / 433 | 7 / 226 | 11 / 227 | 14 / 229 | 0 / 16 | 24 / 391 | 8 / 78 | 3 / 62 | 11 / 348 | 1 / 26 | 134 / 1,054 | 134 / 1,075 | 2 / 18 | 0 / 25 | 13 / 700 | 6 / 285 |
Outcome results
Primary
Percentage of Participants Achieving ≥75% Improvement in Ps Area and Severity Index (PASI75) (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Psoriasis Measure: PASI)
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 (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 achieving PASI75 were defined as having an improvement of ≥75% in the PASI score compared to baseline.
Time frame: Week 12
Population: ITT Population: all randomized participants analyzed according to the treatment to which they were assigned. Participants who did not meet the clinical response criteria or had missing data at Week 12 were considered non-responders for NRI analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving ≥75% Improvement in Ps Area and Severity Index (PASI75) (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Psoriasis Measure: PASI) | 3.9 percentage of participants |
| Ixe Q4W | Percentage of Participants Achieving ≥75% Improvement in Ps Area and Severity Index (PASI75) (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Psoriasis Measure: PASI) | 82.6 percentage of participants |
| Ixe Q2W | Percentage of Participants Achieving ≥75% Improvement in Ps Area and Severity Index (PASI75) (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Psoriasis Measure: PASI) | 89.1 percentage of participants |
p-value: <0.001Regression, Logistic
p-value: <0.001Regression, Logistic
Primary
Percentage of Participants With Static Physician Global Assessment (sPGA) of 0 or 1 (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Ps Measure: sPGA)
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. Participants Ps were 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.
Time frame: Week 12
Population: Intent to Treat (ITT) Population: all randomized participants analyzed according to the treatment to which they were assigned. Participants who did not meet the clinical response criteria or had missing data at Week 12 were considered non-responders for Non-Responder Imputation (NRI) analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Static Physician Global Assessment (sPGA) of 0 or 1 (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Ps Measure: sPGA) | 3.2 percentage of participants |
| Ixe Q4W | Percentage of Participants With Static Physician Global Assessment (sPGA) of 0 or 1 (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Ps Measure: sPGA) | 76.4 percentage of participants |
| Ixe Q2W | Percentage of Participants With Static Physician Global Assessment (sPGA) of 0 or 1 (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Ps Measure: sPGA) | 81.8 percentage of participants |
p-value: <0.001Regression, Logistic
p-value: <0.001Regression, Logistic
Secondary
Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) Quality of Life and Outcome Assessments. Measures: Participant Reported Outcomes (PRO)
WPAI-PSO is a participant administered, 6-item instrument used to assess the impact of Ps on the productivity impairment within the past 7 days. WPAI-PSO has 4 domains: absenteeism, presenteeism (reduced productivity while at work), an overall work impairment score, and impairment in daily activities performed outside of work. Four scores are derived as percentages: absenteeism, presenteeism (reduced productivity while at work), overall work impairment (absenteeism and presenteeism), and impairment in activities performed outside of work. Percentage is calculated as: each score \* 100 with greater scores indicating greater impairment. LS mean change from baseline was calculated using analysis of covariance (ANCOVA).
Time frame: Baseline, Week 12
Population: ITT Population: all randomized participants analyzed according to the treatment to which they are assigned, and had results at specified time points, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) Quality of Life and Outcome Assessments. Measures: Participant Reported Outcomes (PRO) | Absenteeism | 0.2 units on a scale | Standard Error 0.88 |
| Placebo | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) Quality of Life and Outcome Assessments. Measures: Participant Reported Outcomes (PRO) | Activity Impairment | 0.8 units on a scale | Standard Error 1.18 |
| Placebo | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) Quality of Life and Outcome Assessments. Measures: Participant Reported Outcomes (PRO) | Presenteeism | 0.5 units on a scale | Standard Error 1.3 |
| Placebo | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) Quality of Life and Outcome Assessments. Measures: Participant Reported Outcomes (PRO) | Work Productivity Loss | -0.8 units on a scale | Standard Error 1.4 |
| Ixe Q4W | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) Quality of Life and Outcome Assessments. Measures: Participant Reported Outcomes (PRO) | Work Productivity Loss | -20.6 units on a scale | Standard Error 1.38 |
| Ixe Q4W | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) Quality of Life and Outcome Assessments. Measures: Participant Reported Outcomes (PRO) | Absenteeism | -3.5 units on a scale | Standard Error 0.87 |
| Ixe Q4W | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) Quality of Life and Outcome Assessments. Measures: Participant Reported Outcomes (PRO) | Presenteeism | -18.8 units on a scale | Standard Error 1.28 |
| Ixe Q4W | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) Quality of Life and Outcome Assessments. Measures: Participant Reported Outcomes (PRO) | Activity Impairment | -24.5 units on a scale | Standard Error 1.18 |
| Ixe Q2W | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) Quality of Life and Outcome Assessments. Measures: Participant Reported Outcomes (PRO) | Work Productivity Loss | -19.8 units on a scale | Standard Error 1.33 |
| Ixe Q2W | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) Quality of Life and Outcome Assessments. Measures: Participant Reported Outcomes (PRO) | Activity Impairment | -25.2 units on a scale | Standard Error 1.15 |
| Ixe Q2W | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) Quality of Life and Outcome Assessments. Measures: Participant Reported Outcomes (PRO) | Presenteeism | -18.3 units on a scale | Standard Error 1.24 |
| Ixe Q2W | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) Quality of Life and Outcome Assessments. Measures: Participant Reported Outcomes (PRO) | Absenteeism | -2.6 units on a scale | Standard Error 0.84 |
p-value: <0.001ANCOVA
p-value: 0.003ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Change From Baseline in Dermatology-Specific Quality of Life Index (DLQI) Score
DLQI is a participant-administered, 10-question, validated, 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 0 (not at all), 1 (a little), 2 (a lot), and 3 (very much) and unanswered (not relevant) responses were scored as 0. Total scores range from 0 to 30, with higher score indicating greater quality of life is impairment. A 5-point change from baseline is considered clinically relevant. Least squares (LS) mean change from baseline was calculated using mixed model repeated measures (MMRM).
Time frame: Baseline, Week 12
Population: ITT Population: all randomized participants analyzed according to the treatment to which they are assigned; and who had at least 1 post-baseline DLQI measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Dermatology-Specific Quality of Life Index (DLQI) Score | -1.0 units on a scale | Standard Error 0.27 |
| Ixe Q4W | Change From Baseline in Dermatology-Specific Quality of Life Index (DLQI) Score | -10.7 units on a scale | Standard Error 0.27 |
| Ixe Q2W | Change From Baseline in Dermatology-Specific Quality of Life Index (DLQI) Score | -11.1 units on a scale | Standard Error 0.26 |
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
Secondary
Change From Baseline in Medical Outcomes Study 36-item Short Form Health Survey (SF-36) and Physical Component Summary (PCS) and Mental Component Summary (MCS)
The SF-36 is a self-reported instrument that measures the participant's health status during the previous 7 days. 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 in the PCS and MCS scores. Scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. LS mean change from baseline was calculated using ANCOVA.
Time frame: Baseline, Week 12
Population: ITT Population: all randomized participants analyzed according to the treatment to which they are assigned; and with results at the specified time points, LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Medical Outcomes Study 36-item Short Form Health Survey (SF-36) and Physical Component Summary (PCS) and Mental Component Summary (MCS) | PCS | -0.1747 units on a scale | Standard Error 0.4012 |
| Placebo | Change From Baseline in Medical Outcomes Study 36-item Short Form Health Survey (SF-36) and Physical Component Summary (PCS) and Mental Component Summary (MCS) | MCS | 0.8729 units on a scale | Standard Error 0.4638 |
| Ixe Q4W | Change From Baseline in Medical Outcomes Study 36-item Short Form Health Survey (SF-36) and Physical Component Summary (PCS) and Mental Component Summary (MCS) | PCS | 4.3081 units on a scale | Standard Error 0.399 |
| Ixe Q4W | Change From Baseline in Medical Outcomes Study 36-item Short Form Health Survey (SF-36) and Physical Component Summary (PCS) and Mental Component Summary (MCS) | MCS | 3.7386 units on a scale | Standard Error 0.4633 |
| Ixe Q2W | Change From Baseline in Medical Outcomes Study 36-item Short Form Health Survey (SF-36) and Physical Component Summary (PCS) and Mental Component Summary (MCS) | PCS | 4.3159 units on a scale | Standard Error 0.3878 |
| Ixe Q2W | Change From Baseline in Medical Outcomes Study 36-item Short Form Health Survey (SF-36) and Physical Component Summary (PCS) and Mental Component Summary (MCS) | MCS | 4.1293 units on a scale | Standard Error 0.448 |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Change From Baseline in Nail Psoriasis Severity Index (NAPSI)
The NAPSI is a numeric, reproducible, objective tool for evaluation of fingernail Ps. This scale is used to evaluate the severity of fingernail bed Ps and fingernail matrix Ps by area of involvement in the fingernail unit. The fingernail is divided with imaginary horizontal and longitudinal lines into quadrants. Each fingernail is given a score for fingernail bed Ps 0 (none) to 4 (Ps in 4 quadrants of the fingernail) and fingernail matrix Ps 0 (none) to 4 (Ps in 4 quadrants of the matrix), depending on the presence (score of 1) or absence (score of 0) of any of the features of fingernail bed or matrix Ps in each quadrant. The NAPSI score of a fingernail is the sum of scores in fingernail bed and fingernail matrix from each quadrant (maximum of 8). Each fingernail is evaluated, then the sum of all fingernails equals the total NAPSI score with a range from 0 to 80 with higher scores indicating more severe psoriasis. LS mean change from baseline was calculated using MMRM.
Time frame: Baseline, Week 12
Population: ITT Population: all randomized participants analyzed according to the treatment to which they are assigned; and had fingernail Ps at baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Nail Psoriasis Severity Index (NAPSI) | 2.17 units on a scale | Standard Error 0.672 |
| Ixe Q4W | Change From Baseline in Nail Psoriasis Severity Index (NAPSI) | -7.19 units on a scale | Standard Error 0.671 |
| Ixe Q2W | Change From Baseline in Nail Psoriasis Severity Index (NAPSI) | -7.24 units on a scale | Standard Error 0.657 |
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
Secondary
Change From Baseline in Patient's Global Assessment of Disease Severity (PatGA)
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). LS mean change from baseline calculated using MMRM.
Time frame: Baseline, Week 12
Population: ITT Population: all randomized participants analyzed according to the treatment to which they are assigned; and with at least 1 post-baseline PatGA measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Patient's Global Assessment of Disease Severity (PatGA) | -0.2 units on a scale | Standard Error 0.06 |
| Ixe Q4W | Change From Baseline in Patient's Global Assessment of Disease Severity (PatGA) | -3.1 units on a scale | Standard Error 0.06 |
| Ixe Q2W | Change From Baseline in Patient's Global Assessment of Disease Severity (PatGA) | -3.2 units on a scale | Standard Error 0.06 |
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
Secondary
Change From Baseline in Psoriasis Scalp Severity Index (PSSI)
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 scores range from 0 to 72, with lower scores indicating less severity. LS mean change from baseline was calculated using MMRM.
Time frame: Baseline, Week 12
Population: ITT Population: all randomized participants analyzed according to the treatment to which they are assigned; and had scalp Ps at baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Psoriasis Scalp Severity Index (PSSI) | -1.8 units on a scale | Standard Error 0.53 |
| Ixe Q4W | Change From Baseline in Psoriasis Scalp Severity Index (PSSI) | -18.3 units on a scale | Standard Error 0.52 |
| Ixe Q2W | Change From Baseline in Psoriasis Scalp Severity Index (PSSI) | -19.2 units on a scale | Standard Error 0.52 |
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
Secondary
Change From Baseline in Quick Inventory of Depressive Symptomatology-Self Reported 16 Items (QIDS-SR16)
QIDS-SR16 is a participant-administered, 16-item instrument intended to assess the existence and severity of symptoms of depression. A participant is asked to consider each statement as it relates to the way they have felt for the past 7 days and rate each on a 4-point scale: 0 (best) to 3 (worst). The sum of the 16 items corresponding to 9 depression domains \[sad mood, concentration, self-criticism, suicidal ideation, interest, energy/fatigue, sleep disturbance (initial, middle and late insomnia or hypersomnia), decrease/increase in appetite/weight, and psychomotor agitation/retardation\] to give a single total scores range from 0 to 27, with higher scores indicating greater symptom severity. LS mean change from baseline was calculated using ANCOVA.
Time frame: Baseline, Week 12
Population: ITT Population: all randomized participants analyzed according to the treatment to which they are assigned, and had results at the specified time points, LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Quick Inventory of Depressive Symptomatology-Self Reported 16 Items (QIDS-SR16) | -0.1 units on a scale | Standard Error 0.17 |
| Ixe Q4W | Change From Baseline in Quick Inventory of Depressive Symptomatology-Self Reported 16 Items (QIDS-SR16) | -1.0 units on a scale | Standard Error 0.17 |
| Ixe Q2W | Change From Baseline in Quick Inventory of Depressive Symptomatology-Self Reported 16 Items (QIDS-SR16) | -1.3 units on a scale | Standard Error 0.17 |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Percentage of Participants Achieving an sPGA of 0 (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Ps Measure: sPGA)
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. Participants Ps were assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe).
Time frame: Week 12
Population: ITT Population: all randomized participants analyzed according to the treatment to which they are assigned. Participants who did not meet the clinical response criteria or had missing data at Week 12 were considered non-responders for NRI analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving an sPGA of 0 (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Ps Measure: sPGA) | 0.0 percentage of participants |
| Ixe Q4W | Percentage of Participants Achieving an sPGA of 0 (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Ps Measure: sPGA) | 34.5 percentage of participants |
| Ixe Q2W | Percentage of Participants Achieving an sPGA of 0 (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Ps Measure: sPGA) | 37.0 percentage of participants |
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
Secondary
Percentage of Participants Achieving Palmoplantar PASI (PPASI) of ≥50% (PPASI50), ≥75% (PPASI75), or 100% (PPASI100) Improvement
The Palmoplantar PASI is a composite score derived from the sum of scores for erythema, induration, and desquamation \[scores range from 0 (none) to 4 (very severe) for each\] multiplied by the score for the extent of palm and sole area involvement \[scores range from 0 (0%) to 6 (90 to100%)\], with a total scores range from 0 to 72. Participants achieving PPASI50, PPASI75 or PASI100 were defined as having an improvement of at least 50%, 90%, or of 100%, respectively, in the PPASI scores compared to baseline.
Time frame: Week 12
Population: ITT Population: all randomized participants analyzed according to the treatment to which they are assigned; and who had palmoplantar Ps at baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Achieving Palmoplantar PASI (PPASI) of ≥50% (PPASI50), ≥75% (PPASI75), or 100% (PPASI100) Improvement | PPASI100 | 20.3 percentage of participants |
| Placebo | Percentage of Participants Achieving Palmoplantar PASI (PPASI) of ≥50% (PPASI50), ≥75% (PPASI75), or 100% (PPASI100) Improvement | PPASI50 | 35.3 percentage of participants |
| Placebo | Percentage of Participants Achieving Palmoplantar PASI (PPASI) of ≥50% (PPASI50), ≥75% (PPASI75), or 100% (PPASI100) Improvement | PPASI75 | 26.3 percentage of participants |
| Ixe Q4W | Percentage of Participants Achieving Palmoplantar PASI (PPASI) of ≥50% (PPASI50), ≥75% (PPASI75), or 100% (PPASI100) Improvement | PPASI75 | 74.8 percentage of participants |
| Ixe Q4W | Percentage of Participants Achieving Palmoplantar PASI (PPASI) of ≥50% (PPASI50), ≥75% (PPASI75), or 100% (PPASI100) Improvement | PPASI100 | 65.6 percentage of participants |
| Ixe Q4W | Percentage of Participants Achieving Palmoplantar PASI (PPASI) of ≥50% (PPASI50), ≥75% (PPASI75), or 100% (PPASI100) Improvement | PPASI50 | 84.0 percentage of participants |
| Ixe Q2W | Percentage of Participants Achieving Palmoplantar PASI (PPASI) of ≥50% (PPASI50), ≥75% (PPASI75), or 100% (PPASI100) Improvement | PPASI50 | 82.9 percentage of participants |
| Ixe Q2W | Percentage of Participants Achieving Palmoplantar PASI (PPASI) of ≥50% (PPASI50), ≥75% (PPASI75), or 100% (PPASI100) Improvement | PPASI100 | 70.0 percentage of participants |
| Ixe Q2W | Percentage of Participants Achieving Palmoplantar PASI (PPASI) of ≥50% (PPASI50), ≥75% (PPASI75), or 100% (PPASI100) Improvement | PPASI75 | 77.1 percentage of participants |
p-value: <0.001Regression, Logistic
p-value: <0.001Regression, Logistic
p-value: <0.001Regression, Logistic
p-value: <0.001Regression, Logistic
p-value: <0.001Regression, Logistic
p-value: <0.001Regression, Logistic
Secondary
Percentage of Participants Achieving PASI 90% (PASI90) or 100% (PASI100) (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Ps Measure: PASI)
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 (no involvement) to 4 (severe involvement). 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 Ps) to 72 (the most severe disease). Participants achieving PASI90 or PASI100 were defined as having an improvement of ≥90% or of 100% respectively in PASI scores compared to baseline.
Time frame: Week 12
Population: ITT Population: all randomized participants analyzed according to the treatment to which they are assigned. Participants who did not meet the clinical response criteria or had missing data at Week 12 were considered non-responders for NRI analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Achieving PASI 90% (PASI90) or 100% (PASI100) (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Ps Measure: PASI) | PASI90 | 0.5 percentage of participants |
| Placebo | Percentage of Participants Achieving PASI 90% (PASI90) or 100% (PASI100) (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Ps Measure: PASI) | PASI100 | 0.0 percentage of participants |
| Ixe Q4W | Percentage of Participants Achieving PASI 90% (PASI90) or 100% (PASI100) (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Ps Measure: PASI) | PASI90 | 64.6 percentage of participants |
| Ixe Q4W | Percentage of Participants Achieving PASI 90% (PASI90) or 100% (PASI100) (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Ps Measure: PASI) | PASI100 | 33.6 percentage of participants |
| Ixe Q2W | Percentage of Participants Achieving PASI 90% (PASI90) or 100% (PASI100) (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Ps Measure: PASI) | PASI90 | 70.9 percentage of participants |
| Ixe Q2W | Percentage of Participants Achieving PASI 90% (PASI90) or 100% (PASI100) (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Ps Measure: PASI) | PASI100 | 35.3 percentage of participants |
p-value: <0.001Regression, Logistic
p-value: <0.001Regression, Logistic
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
Secondary
Percentage of Participants Maintaining sPGA 0 or 1 After Re-Randomization at Start of Maintenance Dosing Period
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. Participants Ps were assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe).
Time frame: Week 60
Population: Maintenance Period Primary Population (MPPP): all randomized participants from Period 2 who achieved sPGA (0, 1), were re-randomized at Week 12 and who received at least 1 dose of study treatment Period 3. Participants did not meet the clinical response criteria or had missing data at Week 12 were considered non-responders for NRI analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Maintaining sPGA 0 or 1 After Re-Randomization at Start of Maintenance Dosing Period | 7.5 percentage of participants |
| Ixe Q4W | Percentage of Participants Maintaining sPGA 0 or 1 After Re-Randomization at Start of Maintenance Dosing Period | 37.4 percentage of participants |
| Ixe Q2W | Percentage of Participants Maintaining sPGA 0 or 1 After Re-Randomization at Start of Maintenance Dosing Period | 72.9 percentage of participants |
p-value: <0.001Regression, Logistic
p-value: <0.001Regression, Logistic
Secondary
Percentage of Participants With Anti-ixekizumab Antibodies
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%.
Time frame: Baseline through Week 12
Population: All randomized participants who received at least 1 dose of study drug and had evaluable data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Anti-ixekizumab Antibodies | 0.5 percentage of participants |
| Ixe Q4W | Percentage of Participants With Anti-ixekizumab Antibodies | 12.5 percentage of participants |
| Ixe Q2W | Percentage of Participants With Anti-ixekizumab Antibodies | 10.3 percentage of participants |
Secondary
Percentage of Participants With Itch Numeric Rating Scale (Itch NRS) Score ≥4 Point Reduction From Baseline
The Itch NRS is a participant-administered, 11-point horizontal scale anchored at 0 (no itch) and 10 (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.
Time frame: Baseline, Week 12
Population: ITT Population: all randomized participants analyzed according to the treatment to which they are assigned; and had an Itch NRS score ≥4 at baseline. Participants who did not meet the clinical response criteria or had missing data at Week 12 were considered non-responders for NRI analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Itch Numeric Rating Scale (Itch NRS) Score ≥4 Point Reduction From Baseline | 15.5 percentage of participants |
| Ixe Q4W | Percentage of Participants With Itch Numeric Rating Scale (Itch NRS) Score ≥4 Point Reduction From Baseline | 80.5 percentage of participants |
| Ixe Q2W | Percentage of Participants With Itch Numeric Rating Scale (Itch NRS) Score ≥4 Point Reduction From Baseline | 85.9 percentage of participants |
p-value: <0.001Regression, Logistic
p-value: <0.001Regression, Logistic
Secondary
Percent of Body Surface Area (BSA) Involvement of Ps
BSA is a physician rating of the percentage of involvement of Ps for each participant. BSA is assessed on a continuous scale from 0% (no involvement) to 100% (full involvement), where 1% corresponds to the size of the participants hand (includes the palm, fingers and thumb). Total BSA is the sum of handprints from the affected areas. LS mean change from baseline was calculated using MMRM.
Time frame: Week 12
Population: ITT Population: all randomized participants analyzed according to the treatment to which they are assigned; and had at least 1 post-baseline BSA measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent of Body Surface Area (BSA) Involvement of Ps | 1.3 percentage of body surface | Standard Error 0.67 |
| Ixe Q4W | Percent of Body Surface Area (BSA) Involvement of Ps | -21.4 percentage of body surface | Standard Error 0.67 |
| Ixe Q2W | Percent of Body Surface Area (BSA) Involvement of Ps | -22.4 percentage of body surface | Standard Error 0.66 |
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
Secondary
Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough ss)
Time frame: Weeks 12: Day 84 and Week 24: Day 168
Population: ITT Population: all randomized participants analyzed according to the treatment to which they are assigned; and who had Ctrough ss results at specified time points where the concentration met the definition of being a trough concentration.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough ss) | Week 12 | 7.73 micrograms/milliliter (µg/mL) | Geometric Coefficient of Variation 79 |
| Placebo | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough ss) | Week 24 | NA micrograms/milliliter (µg/mL) | — |
| Ixe Q4W | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough ss) | Week 24 | NA micrograms/milliliter (µg/mL) | — |
| Ixe Q4W | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough ss) | Week 12 | 2.94 micrograms/milliliter (µg/mL) | Geometric Coefficient of Variation 89 |
| Ixe Q2W | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough ss) | Week 12 | NA micrograms/milliliter (µg/mL) | — |
| Ixe Q2W | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough ss) | Week 24 | 2.36 micrograms/milliliter (µg/mL) | Geometric Coefficient of Variation 111 |
| Ixe Q12W - Maintenance Period | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough ss) | Week 12 | NA micrograms/milliliter (µg/mL) | — |
| Ixe Q12W - Maintenance Period | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough ss) | Week 24 | 0.281 micrograms/milliliter (µg/mL) | Geometric Coefficient of Variation 175 |