Plaque Psoriasis
Conditions
Brief summary
The main purpose of this study is to evaluate the efficacy of ixekizumab dosing regimens in participants with plaque psoriasis.
Detailed description
The purpose of this study is to evaluate both the safety and efficacy of ixekizumab dosing regimens. There are 3 study periods: Screening Period, Blinded Treatment Dosing Period, and Post-Treatment Follow-Up.
Interventions
DRUGIxekizumab
Administered SQ
DRUGPlacebo
Administered SQ
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Present with chronic plaque psoriasis for at least 6 months prior to enrollment * At least 10% BSA of psoriasis at screening and at enrollment * sPGA score of at least 3 and PASI score of at least 12 at screening and at enrollment * Candidates for phototherapy and/or systemic therapy * Participant must agree to use reliable method of birth control during the study; women must continue using birth control for at least 12 weeks after stopping treatment
Exclusion criteria
* Predominant pattern of pustular, erythrodermic, or guttate forms of psoriasis * History of drug-induced psoriasis * Cannot avoid excessive sun exposure or use of tanning booths for at least 4 weeks prior to enrollment and during the study * Received systemic non-biologic psoriasis therapy or phototherapy within the previous 4 weeks; or had topical psoriasis treatment within the previous 2 weeks prior to enrollment * Concurrent or recent use of any biologic agent * Have participated in any study with ixekizumab * Received a live vaccination within 12 weeks prior to enrollment * Serious disorder or illness other than psoriasis * Ongoing or serious infection within the last 12 weeks or evidence of tuberculosis * Major surgery within 8 weeks of baseline, or will require surgery during the study * Breastfeeding or nursing (lactating) women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Static Physician Global Assessment (sPGA) of (0,1) | Week 52 | The sPGA is the physician's determination of the participant's Psoriasis (Ps) lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participant's Ps was assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe). An sPGA responder was defined as having a post-baseline sPGA score of 0 or 1 with at least a 2-point improvement from baseline. Participants who did not meet the clinical response criteria or had missing data at Week 52 were considered non-responders for Non-Responder Imputation (NRI) analysis. |
| Percentage of Participants Achieving 75% Improvement in Psoriasis Area and Severity Index (PASI 75) | Week 52 | The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no Ps to 72 for the most severe disease. For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region \* area score \* weighing factor \[head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)\]. Overall scores range from 0 (no Ps) to 72 (the most severe disease). Participants who did not meet the clinical response criteria or had missing data at Week52 were considered non-responders for NRI analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving PASI 100 | Week 52 | The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no Ps to 72 for the most severe disease. For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region \* area score \* weighing factor \[head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)\]. Overall scores range from 0 (no Ps) to 72 (the most severe disease). |
| Change From Baseline in PASI | Baseline, Week 52 | The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no Ps to 72 for the most severe disease. Least Squares mean (LSmean) was calculated using Mixed-Effects Model of Repeated Measures (MMRM) analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured. |
| Percent Improvement in PASI | Baseline, Week 52 | The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no Ps to 72 for the most severe disease. Least Squares mean (LSmean) was calculated using Mixed-Effects Model of Repeated Measures (MMRM) analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured. |
| Mean Change From Baseline in Percent Body Surface Area (BSA) Involvement | Baseline, Week 52 | The percentage involvement of psoriasis on each participant's body surface area (BSA) was assessed by the investigator on a continuous scale from 0% (no involvement) to 100% (full involvement), in which 1% corresponds to the size of the participant's hand including palm, fingers and thumb. LS mean was calculated using MMRM analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured. |
| Mean Change From Baseline in Nail Psoriasis Severity Index (NAPSI) Score | Baseline, Week 52 | The NAPSI is a numeric, reproducible, objective tool for evaluation of fingernail (fn) Ps. This scale is used to evaluate the severity of fn bed Ps and fn matrix Ps by area of involvement in the fn unit. The fn is divided with imaginary horizontal and longitudinal lines into quadrants. Each fn is given a score for fn bed Ps (0 to 4) and fn matrix Ps (0 to 4) depending on presence (score of 1) or absence (score of 0) of any of the features of fn bed and fn matrix Ps in each quadrant. The NAPSI score of a fn is sum of scores in fn bed and fn matrix from each quadrant (maximum of 8). Each fn is evaluated, then the sum of all fn equals the total NAPSI score with a range from 0 to 80 (0 indicates no Ps, 80 indicates worst Ps). LS mean was calculated using MMRM analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured. |
| Mean Change From Baseline in Psoriasis Scalp Severity Index (PSSI) Score | Baseline, Week 52 | 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 score ranging from 0 (less severity) to 72 (more severity). LS mean change was calculated using MMRM analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured. |
| Mean Change From Baseline in Palmoplantar PASI (PPASI) | Baseline, Week 52 | The Palmoplantar PASI is a composite score derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement, ranging from 0 (no PPASI) to 72 (most severe PPASI). The PPASI was only assessed if participants have palmoplantar psoriasis at baseline. LS mean was calculated using MMRM analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured. |
| Percentage of Participants Achieving sPGA (0) | Week 52 | The sPGA is the physician's determination of the participant's Ps lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participant's Ps was assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe). An sPGA responder was defined as having a post-baseline sPGA score of 0 or 1 with at least a 2-point improvement from baseline. Participants who did not meet the clinical response criteria or had missing data at Week 52 were considered non-responders for Non-Responder Imputation (NRI) analysis. |
| Percentage of Participants Achieving Dermatology Life Quality Index (DLQI) Total Score of 0 and 1 (DLQI [0,1]) | Week 52 | The DLQI is a simple, participant-administered, 10 question, validated, quality-of-life questionnaire that covers 6 domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include not at all, a lot, and very much, with corresponding scores of 1, 2, and 3, respectively, and unanswered (not relevant) responses scored as 0. Totals range from 0 to 30 (less to more impairment). Participants who did not meet the clinical response criteria or had missing data at Week 52 were considered non-responders for Non-Responder Imputation (NRI) analysis. |
| Change From Baseline in DLQI Total Score | Baseline, Week 52 | The DLQI is a simple, participant-administered, 10 question, validated, quality-of-life questionnaire that covers 6 domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include not at all, a lot, and very much, with corresponding scores of 1, 2, and 3, respectively, and unanswered (not relevant) responses scored as 0. Totals range from 0 to 30 (less to more impairment). LS mean change was calculated using MMRM analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured. |
| Change From Baseline in Itch NRS Score | Baseline, Week 52 | The Itch NRS is a participant-administered single-item 11-point horizontal scale anchored at 0 and 10, with 0 representing no itch and 10 representing 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. LS mean change from baseline in PSSI was calculated using MMRM analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured. |
| Change From Baseline in Skin Pain Visual Analog Scale (VAS) | Baseline, Week 52 | The pain VAS is a participant-administered single-item scale designed to measure Skin pain from Psoriasis using a 0-100 millimeter (mm) horizontal VAS. Overall severity of participant's skin pain from Psoriasis is indicated by placing a single mark on the horizontal 100 mm scale from 0 mm (no skin pain) to 100 mm (severe skin pain). LS mean was calculated using MMRM analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured. |
| Change From Baseline in European Quality of Life - 5 Dimensions 5 Level (EQ-5D-5L) VAS | Baseline, Week 52 | EQ-5D-5L is a standardized measure of health status used to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L consists of 2 components: a descriptive system of the respondent's health and a rating of his/her current health state using a 0 (no pain) to 100mm VAS (severe pain). LS mean was calculated using MMRM analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured. |
| Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough,ss) of Ixekizumab | Predose, Week 4, 12, 24, 36 and 52 Post dose | Trough concentrations at steady state of Ixekizumab were evaluated. |
| Number of Participants With Anti-Ixekizumab Antibodies | Baseline through Week 52 | Number of participants with treatment-emergent positive anti-ixekizumab antibodies was summarized by treatment group. |
| Percentage of Participants Achieving an Itch Numeric Rating Scale (Itch NRS) ≥4 Point Reduction From Baseline | Baseline, Week 52 | The Itch NRS is a participant-administered single-item 11-point horizontal scale anchored at 0 and 10, with 0 representing no itch and 10 representing 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. Participants who did not meet the clinical response criteria or had missing data at Week 52 were considered non-responders for Non-Responder Imputation (NRI) analysis. |
| Percentage of Participants Achieving PASI 90 | Week 52 | PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no Ps to 72 for the most severe disease. For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region \* area score \* weighing factor \[head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)\]. Overall scores range from 0 (no Ps) to 72 (the most severe disease). |
Countries
Argentina, Australia, Canada, Czechia, Germany, Hungary, Japan, Mexico, Poland, Puerto Rico, Romania, South Korea, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 80 mg Ixekizumab Q4W 160 mg ixekizumab given as 2 SQ injections at baseline and then 80 mg ixekizumab given as 1 SQ injection Q4W to week 52. Placebo administered SQ, Q2W to maintain blind. | 310 |
| 80 mg Ixekizumab Q4W/Q2W 160 mg ixekizumab given as 2 SQ injections at baseline and then 80 mg ixekizumab given as one SQ injection Q4W with step-up dosing to Q2W as needed (Q4W/Q2W step-up) to week 52. Placebo administered SQ, Q2W to maintain blind. | 306 |
| 80 mg Ixekizumab Q2W 160 mg ixekizumab given as 2 SQ injections at baseline and then 80 mg ixekizumab given as 1 SQ injection Q2W to week 52. Placebo administered SQ, Q2W to maintain blind. | 611 |
| 80 mg Ixekizumab Q4W Maximum Extended Enrollment Cohort 160 mg ixekizumab given as 2 SQ injections at baseline and then 80 mg ixekizumab given as 1 SQ injection Q4W to week 52. Placebo administered SQ, Q2W to maintain blind. | 9 |
| 80 mg Ixekizumab Q4W/Q2W Maximum Extended Enrollment Cohort 160 mg ixekizumab given as 2 SQ injections at baseline and then 80 mg ixekizumab given as one SQ injection Q4W with step-up dosing to Q2W as needed (Q4W/Q2W step-up) to week 52. Placebo administered SQ, Q2W to maintain blind. | 5 |
| 80 mg Ixekizumab Q2W Maximum Extended Enrollment Cohort 160 mg ixekizumab given as 2 SQ injections at baseline and then 80 mg ixekizumab given as 1 SQ injection Q2W to week 52. Placebo administered SQ, Q2W to maintain blind. | 16 |
| Total | 1,257 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Double Blind Treatment Period | Adverse Event | 5 | 13 | 17 | 0 | 1 | 0 |
| Double Blind Treatment Period | Death | 1 | 0 | 2 | 0 | 0 | 0 |
| Double Blind Treatment Period | Due to personal business | 2 | 0 | 1 | 0 | 0 | 0 |
| Double Blind Treatment Period | Lack of Efficacy | 4 | 5 | 6 | 0 | 0 | 0 |
| Double Blind Treatment Period | Lost to Follow-up | 9 | 7 | 11 | 0 | 0 | 1 |
| Double Blind Treatment Period | Met exclusion criteria and was not dosed | 0 | 0 | 1 | 0 | 0 | 0 |
| Double Blind Treatment Period | Physician Decision | 2 | 0 | 4 | 0 | 0 | 0 |
| Double Blind Treatment Period | Protocol Violation | 1 | 1 | 4 | 0 | 0 | 0 |
| Double Blind Treatment Period | Site terminated by sponsor | 1 | 1 | 3 | 0 | 0 | 0 |
| Double Blind Treatment Period | Withdrawal by Subject | 11 | 11 | 25 | 0 | 0 | 0 |
| Post-Treatment Follow-up Period | Adverse Event | 1 | 1 | 4 | 0 | 0 | 0 |
| Post-Treatment Follow-up Period | Death | 0 | 0 | 1 | 0 | 0 | 0 |
| Post-Treatment Follow-up Period | Early terminated but completed follow-up | 12 | 16 | 20 | 0 | 0 | 0 |
| Post-Treatment Follow-up Period | Labor Reasons | 0 | 0 | 1 | 0 | 0 | 0 |
| Post-Treatment Follow-up Period | Lost to Follow-up | 4 | 2 | 7 | 0 | 0 | 0 |
| Post-Treatment Follow-up Period | Physician Decision | 2 | 0 | 0 | 0 | 0 | 0 |
| Post-Treatment Follow-up Period | Subject did not come for Visit-802 | 0 | 0 | 3 | 0 | 0 | 0 |
| Post-Treatment Follow-up Period | Subject move out of town | 0 | 0 | 1 | 0 | 0 | 0 |
| Post-Treatment Follow-up Period | Withdrawal by Subject | 12 | 20 | 26 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | 80 mg Ixekizumab Q4W | 80 mg Ixekizumab Q4W/Q2W | 80 mg Ixekizumab Q2W | 80 mg Ixekizumab Q4W Maximum Extended Enrollment Cohort | 80 mg Ixekizumab Q4W/Q2W Maximum Extended Enrollment Cohort | 80 mg Ixekizumab Q2W Maximum Extended Enrollment Cohort | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 47.4 years STANDARD_DEVIATION 13.5 | 45.9 years STANDARD_DEVIATION 12.85 | 49.0 years STANDARD_DEVIATION 13.61 | 40.0 years STANDARD_DEVIATION 9.62 | 46.0 years STANDARD_DEVIATION 13.17 | 46.1 years STANDARD_DEVIATION 13.05 | 47.8 years STANDARD_DEVIATION 13.45 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 59 Participants | 55 Participants | 111 Participants | 0 Participants | 0 Participants | 0 Participants | 225 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 243 Participants | 244 Participants | 489 Participants | 9 Participants | 5 Participants | 16 Participants | 1006 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants | 7 Participants | 11 Participants | 0 Participants | 0 Participants | 0 Participants | 26 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 11 Participants | 12 Participants | 23 Participants | 0 Participants | 0 Participants | 0 Participants | 46 Participants |
| Race (NIH/OMB) Asian | 31 Participants | 32 Participants | 64 Participants | 9 Participants | 5 Participants | 16 Participants | 157 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 8 Participants | 22 Participants | 0 Participants | 0 Participants | 0 Participants | 44 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 12 Participants | 0 Participants | 0 Participants | 0 Participants | 16 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 251 Participants | 253 Participants | 486 Participants | 0 Participants | 0 Participants | 0 Participants | 990 Participants |
| Region of Enrollment Argentina | 9 Participants | 9 Participants | 19 Participants | 0 Participants | 0 Participants | 0 Participants | 37 Participants |
| Region of Enrollment Australia | 14 Participants | 14 Participants | 28 Participants | 0 Participants | 0 Participants | 0 Participants | 56 Participants |
| Region of Enrollment Canada | 49 Participants | 49 Participants | 99 Participants | 0 Participants | 0 Participants | 0 Participants | 197 Participants |
| Region of Enrollment Czechia | 3 Participants | 3 Participants | 8 Participants | 0 Participants | 0 Participants | 0 Participants | 14 Participants |
| Region of Enrollment Germany | 12 Participants | 11 Participants | 18 Participants | 0 Participants | 0 Participants | 0 Participants | 41 Participants |
| Region of Enrollment Hungary | 11 Participants | 10 Participants | 23 Participants | 0 Participants | 0 Participants | 0 Participants | 44 Participants |
| Region of Enrollment Japan | 5 Participants | 2 Participants | 9 Participants | 0 Participants | 0 Participants | 0 Participants | 16 Participants |
| Region of Enrollment Mexico | 10 Participants | 8 Participants | 17 Participants | 0 Participants | 0 Participants | 0 Participants | 35 Participants |
| Region of Enrollment Poland | 43 Participants | 43 Participants | 83 Participants | 0 Participants | 0 Participants | 0 Participants | 169 Participants |
| Region of Enrollment Puerto Rico | 14 Participants | 16 Participants | 29 Participants | 0 Participants | 0 Participants | 0 Participants | 59 Participants |
| Region of Enrollment Romania | 5 Participants | 5 Participants | 9 Participants | 0 Participants | 0 Participants | 0 Participants | 19 Participants |
| Region of Enrollment South Korea | 11 Participants | 12 Participants | 22 Participants | 9 Participants | 5 Participants | 16 Participants | 75 Participants |
| Region of Enrollment Taiwan | 5 Participants | 6 Participants | 9 Participants | 0 Participants | 0 Participants | 0 Participants | 20 Participants |
| Region of Enrollment United States | 119 Participants | 118 Participants | 238 Participants | 0 Participants | 0 Participants | 0 Participants | 475 Participants |
| Sex: Female, Male Female | 111 Participants | 107 Participants | 199 Participants | 2 Participants | 0 Participants | 4 Participants | 423 Participants |
| Sex: Female, Male Male | 199 Participants | 199 Participants | 412 Participants | 7 Participants | 5 Participants | 12 Participants | 834 Participants |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 310 | 0 / 306 | 0 / 609 | 0 / 285 | 0 / 283 | 0 / 559 | 0 / 9 | 0 / 5 | 0 / 16 | 0 / 9 | 0 / 4 | 0 / 15 |
| other Total, other adverse events | 157 / 310 | 136 / 306 | 285 / 609 | 16 / 285 | 20 / 283 | 40 / 559 | 6 / 9 | 4 / 5 | 11 / 16 | 2 / 9 | 0 / 4 | 2 / 15 |
| serious Total, serious adverse events | 16 / 310 | 16 / 306 | 32 / 609 | 1 / 285 | 2 / 283 | 7 / 559 | 0 / 9 | 1 / 5 | 0 / 16 | 0 / 9 | 0 / 4 | 0 / 15 |
Outcome results
Primary
Percentage of Participants Achieving 75% Improvement in Psoriasis Area and Severity Index (PASI 75)
The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no Ps to 72 for the most severe disease. For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region \* area score \* weighing factor \[head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)\]. Overall scores range from 0 (no Ps) to 72 (the most severe disease). Participants who did not meet the clinical response criteria or had missing data at Week52 were considered non-responders for NRI analysis.
Time frame: Week 52
Population: All randomized participants analyzed according to the treatment to which they were assigned. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 80 mg Ixekizumab Q4W | Percentage of Participants Achieving 75% Improvement in Psoriasis Area and Severity Index (PASI 75) | 79 Percentage of participants |
| 80 mg Ixekizumab Q4W/Q2W | Percentage of Participants Achieving 75% Improvement in Psoriasis Area and Severity Index (PASI 75) | 83.7 Percentage of participants |
| 80 mg Ixekizumab Q2W | Percentage of Participants Achieving 75% Improvement in Psoriasis Area and Severity Index (PASI 75) | 85.9 Percentage of participants |
p-value: =0.006Regression, Logistic
p-value: =0.118Regression, Logistic
Primary
Percentage of Participants Achieving Static Physician Global Assessment (sPGA) of (0,1)
The sPGA is the physician's determination of the participant's Psoriasis (Ps) lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participant's Ps was assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe). An sPGA responder was defined as having a post-baseline sPGA score of 0 or 1 with at least a 2-point improvement from baseline. Participants who did not meet the clinical response criteria or had missing data at Week 52 were considered non-responders for Non-Responder Imputation (NRI) analysis.
Time frame: Week 52
Population: All randomized participants analyzed according to the treatment to which they were assigned. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 80 mg Ixekizumab Q4W | Percentage of Participants Achieving Static Physician Global Assessment (sPGA) of (0,1) | 70.6 Percentage of participants |
| 80 mg Ixekizumab Q4W/Q2W | Percentage of Participants Achieving Static Physician Global Assessment (sPGA) of (0,1) | 72.5 Percentage of participants |
| 80 mg Ixekizumab Q2W | Percentage of Participants Achieving Static Physician Global Assessment (sPGA) of (0,1) | 78.6 Percentage of participants |
p-value: =0.005Regression, Logistic
p-value: =0.522Regression, Logistic
Secondary
Change From Baseline in DLQI Total Score
The DLQI is a simple, participant-administered, 10 question, validated, quality-of-life questionnaire that covers 6 domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include not at all, a lot, and very much, with corresponding scores of 1, 2, and 3, respectively, and unanswered (not relevant) responses scored as 0. Totals range from 0 to 30 (less to more impairment). LS mean change was calculated using MMRM analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured.
Time frame: Baseline, Week 52
Population: All randomized participants analyzed according to the treatment to which they were assigned and who had baseline and post-baseline DLQI data. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg Ixekizumab Q4W | Change From Baseline in DLQI Total Score | -9.70 units on a scale | Standard Error 0.21 |
| 80 mg Ixekizumab Q4W/Q2W | Change From Baseline in DLQI Total Score | -9.97 units on a scale | Standard Error 0.22 |
| 80 mg Ixekizumab Q2W | Change From Baseline in DLQI Total Score | -10.23 units on a scale | Standard Error 0.17 |
Secondary
Change From Baseline in European Quality of Life - 5 Dimensions 5 Level (EQ-5D-5L) VAS
EQ-5D-5L is a standardized measure of health status used to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L consists of 2 components: a descriptive system of the respondent's health and a rating of his/her current health state using a 0 (no pain) to 100mm VAS (severe pain). LS mean was calculated using MMRM analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured.
Time frame: Baseline, Week 52
Population: All randomized participants analyzed according to the treatment to which they were assigned and who had baseline and post baseline EQ-5D-5L VAS data. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg Ixekizumab Q4W | Change From Baseline in European Quality of Life - 5 Dimensions 5 Level (EQ-5D-5L) VAS | 11.93 mm | Standard Error 0.94 |
| 80 mg Ixekizumab Q4W/Q2W | Change From Baseline in European Quality of Life - 5 Dimensions 5 Level (EQ-5D-5L) VAS | 12.47 mm | Standard Error 0.95 |
| 80 mg Ixekizumab Q2W | Change From Baseline in European Quality of Life - 5 Dimensions 5 Level (EQ-5D-5L) VAS | 14.42 mm | Standard Error 0.74 |
Secondary
Change From Baseline in Itch NRS Score
The Itch NRS is a participant-administered single-item 11-point horizontal scale anchored at 0 and 10, with 0 representing no itch and 10 representing 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. LS mean change from baseline in PSSI was calculated using MMRM analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured.
Time frame: Baseline, Week 52
Population: All randomized participants analyzed according to the treatment to which they were assigned and who had baseline and post-baseline Itch NRS data. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg Ixekizumab Q4W | Change From Baseline in Itch NRS Score | -4.90 units on a scale | Standard Error 0.13 |
| 80 mg Ixekizumab Q4W/Q2W | Change From Baseline in Itch NRS Score | -5.15 units on a scale | Standard Error 0.13 |
| 80 mg Ixekizumab Q2W | Change From Baseline in Itch NRS Score | -5.33 units on a scale | Standard Error 0.1 |
Secondary
Change From Baseline in PASI
The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no Ps to 72 for the most severe disease. Least Squares mean (LSmean) was calculated using Mixed-Effects Model of Repeated Measures (MMRM) analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured.
Time frame: Baseline, Week 52
Population: All randomized participants analyzed according to the treatment to which they were assigned and had a baseline and post-baseline measurement for PASI. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg Ixekizumab Q4W | Change From Baseline in PASI | -18.34 units on a scale | Standard Error 0.22 |
| 80 mg Ixekizumab Q4W/Q2W | Change From Baseline in PASI | -18.95 units on a scale | Standard Error 0.22 |
| 80 mg Ixekizumab Q2W | Change From Baseline in PASI | -19.41 units on a scale | Standard Error 0.17 |
Secondary
Change From Baseline in Skin Pain Visual Analog Scale (VAS)
The pain VAS is a participant-administered single-item scale designed to measure Skin pain from Psoriasis using a 0-100 millimeter (mm) horizontal VAS. Overall severity of participant's skin pain from Psoriasis is indicated by placing a single mark on the horizontal 100 mm scale from 0 mm (no skin pain) to 100 mm (severe skin pain). LS mean was calculated using MMRM analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured.
Time frame: Baseline, Week 52
Population: All randomized participants analyzed according to the treatment to which they were assigned and who had baseline and post-baseline skin pain VAS data. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg Ixekizumab Q4W | Change From Baseline in Skin Pain Visual Analog Scale (VAS) | -35.50 mm | Standard Error 0.94 |
| 80 mg Ixekizumab Q4W/Q2W | Change From Baseline in Skin Pain Visual Analog Scale (VAS) | -36.77 mm | Standard Error 0.96 |
| 80 mg Ixekizumab Q2W | Change From Baseline in Skin Pain Visual Analog Scale (VAS) | -38.07 mm | Standard Error 0.74 |
Secondary
Mean Change From Baseline in Nail Psoriasis Severity Index (NAPSI) Score
The NAPSI is a numeric, reproducible, objective tool for evaluation of fingernail (fn) Ps. This scale is used to evaluate the severity of fn bed Ps and fn matrix Ps by area of involvement in the fn unit. The fn is divided with imaginary horizontal and longitudinal lines into quadrants. Each fn is given a score for fn bed Ps (0 to 4) and fn matrix Ps (0 to 4) depending on presence (score of 1) or absence (score of 0) of any of the features of fn bed and fn matrix Ps in each quadrant. The NAPSI score of a fn is sum of scores in fn bed and fn matrix from each quadrant (maximum of 8). Each fn is evaluated, then the sum of all fn equals the total NAPSI score with a range from 0 to 80 (0 indicates no Ps, 80 indicates worst Ps). LS mean was calculated using MMRM analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured.
Time frame: Baseline, Week 52
Population: All randomized participants analyzed according to the treatment to which they were assigned who had baseline fingernail involvement and had a post-baseline measurement. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg Ixekizumab Q4W | Mean Change From Baseline in Nail Psoriasis Severity Index (NAPSI) Score | -19.27 units on a scale | Standard Error 0.81 |
| 80 mg Ixekizumab Q4W/Q2W | Mean Change From Baseline in Nail Psoriasis Severity Index (NAPSI) Score | -19.87 units on a scale | Standard Error 0.83 |
| 80 mg Ixekizumab Q2W | Mean Change From Baseline in Nail Psoriasis Severity Index (NAPSI) Score | -20.82 units on a scale | Standard Error 0.62 |
Secondary
Mean Change From Baseline in Palmoplantar PASI (PPASI)
The Palmoplantar PASI is a composite score derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement, ranging from 0 (no PPASI) to 72 (most severe PPASI). The PPASI was only assessed if participants have palmoplantar psoriasis at baseline. LS mean was calculated using MMRM analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured.
Time frame: Baseline, Week 52
Population: All randomized participants analyzed according to the treatment to which they were assigned and had baseline palmoplantar Ps involvement and had post-baseline measurement. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg Ixekizumab Q4W | Mean Change From Baseline in Palmoplantar PASI (PPASI) | -9.55 units on a scale | Standard Error 0.31 |
| 80 mg Ixekizumab Q4W/Q2W | Mean Change From Baseline in Palmoplantar PASI (PPASI) | -9.37 units on a scale | Standard Error 0.3 |
| 80 mg Ixekizumab Q2W | Mean Change From Baseline in Palmoplantar PASI (PPASI) | -9.00 units on a scale | Standard Error 0.26 |
Secondary
Mean Change From Baseline in Percent Body Surface Area (BSA) Involvement
The percentage involvement of psoriasis on each participant's body surface area (BSA) was assessed by the investigator on a continuous scale from 0% (no involvement) to 100% (full involvement), in which 1% corresponds to the size of the participant's hand including palm, fingers and thumb. LS mean was calculated using MMRM analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured.
Time frame: Baseline, Week 52
Population: All randomized participants analyzed according to the treatment to which they were assigned who had baseline and a post-baseline measurement for BSA affected by Psoriasis. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg Ixekizumab Q4W | Mean Change From Baseline in Percent Body Surface Area (BSA) Involvement | -23.93 Percent Body Surface Affected | Standard Error 0.34 |
| 80 mg Ixekizumab Q4W/Q2W | Mean Change From Baseline in Percent Body Surface Area (BSA) Involvement | -24.62 Percent Body Surface Affected | Standard Error 0.34 |
| 80 mg Ixekizumab Q2W | Mean Change From Baseline in Percent Body Surface Area (BSA) Involvement | -25.01 Percent Body Surface Affected | Standard Error 0.27 |
Secondary
Mean Change From Baseline in Psoriasis Scalp Severity Index (PSSI) Score
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 score ranging from 0 (less severity) to 72 (more severity). LS mean change was calculated using MMRM analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured.
Time frame: Baseline, Week 52
Population: All randomized participants analyzed according to the treatment to which they were assigned and had baseline scalp involvement and had a post-baseline measurement. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg Ixekizumab Q4W | Mean Change From Baseline in Psoriasis Scalp Severity Index (PSSI) Score | -18.35 units on a scale | Standard Error 0.31 |
| 80 mg Ixekizumab Q4W/Q2W | Mean Change From Baseline in Psoriasis Scalp Severity Index (PSSI) Score | -18.73 units on a scale | Standard Error 0.31 |
| 80 mg Ixekizumab Q2W | Mean Change From Baseline in Psoriasis Scalp Severity Index (PSSI) Score | -18.65 units on a scale | Standard Error 0.24 |
Secondary
Number of Participants With Anti-Ixekizumab Antibodies
Number of participants with treatment-emergent positive anti-ixekizumab antibodies was summarized by treatment group.
Time frame: Baseline through Week 52
Population: All randomized participants who received at least 1 dose of Ixekizumab and had evaluable anti-ixekizumab antibody measurement. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 80 mg Ixekizumab Q4W | Number of Participants With Anti-Ixekizumab Antibodies | 71 participants |
| 80 mg Ixekizumab Q4W/Q2W | Number of Participants With Anti-Ixekizumab Antibodies | 64 participants |
| 80 mg Ixekizumab Q2W | Number of Participants With Anti-Ixekizumab Antibodies | 84 participants |
Secondary
Percentage of Participants Achieving an Itch Numeric Rating Scale (Itch NRS) ≥4 Point Reduction From Baseline
The Itch NRS is a participant-administered single-item 11-point horizontal scale anchored at 0 and 10, with 0 representing no itch and 10 representing 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. Participants who did not meet the clinical response criteria or had missing data at Week 52 were considered non-responders for Non-Responder Imputation (NRI) analysis.
Time frame: Baseline, Week 52
Population: All randomized participants analyzed according to the treatment to which they were assigned and who had baseline Itch NRS score greater than or equal to (\>=) 4. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 80 mg Ixekizumab Q4W | Percentage of Participants Achieving an Itch Numeric Rating Scale (Itch NRS) ≥4 Point Reduction From Baseline | 74.0 Percentage of participants |
| 80 mg Ixekizumab Q4W/Q2W | Percentage of Participants Achieving an Itch Numeric Rating Scale (Itch NRS) ≥4 Point Reduction From Baseline | 72.3 Percentage of participants |
| 80 mg Ixekizumab Q2W | Percentage of Participants Achieving an Itch Numeric Rating Scale (Itch NRS) ≥4 Point Reduction From Baseline | 77.2 Percentage of participants |
Secondary
Percentage of Participants Achieving Dermatology Life Quality Index (DLQI) Total Score of 0 and 1 (DLQI [0,1])
The DLQI is a simple, participant-administered, 10 question, validated, quality-of-life questionnaire that covers 6 domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include not at all, a lot, and very much, with corresponding scores of 1, 2, and 3, respectively, and unanswered (not relevant) responses scored as 0. Totals range from 0 to 30 (less to more impairment). Participants who did not meet the clinical response criteria or had missing data at Week 52 were considered non-responders for Non-Responder Imputation (NRI) analysis.
Time frame: Week 52
Population: All randomized participants analyzed according to the treatment to which they were assigned. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 80 mg Ixekizumab Q4W | Percentage of Participants Achieving Dermatology Life Quality Index (DLQI) Total Score of 0 and 1 (DLQI [0,1]) | 66.1 Percentage of participants |
| 80 mg Ixekizumab Q4W/Q2W | Percentage of Participants Achieving Dermatology Life Quality Index (DLQI) Total Score of 0 and 1 (DLQI [0,1]) | 70.3 Percentage of participants |
| 80 mg Ixekizumab Q2W | Percentage of Participants Achieving Dermatology Life Quality Index (DLQI) Total Score of 0 and 1 (DLQI [0,1]) | 74.0 Percentage of participants |
Secondary
Percentage of Participants Achieving PASI 100
The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no Ps to 72 for the most severe disease. For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region \* area score \* weighing factor \[head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)\]. Overall scores range from 0 (no Ps) to 72 (the most severe disease).
Time frame: Week 52
Population: All randomized participants analyzed according to the treatment to which they were assigned. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 80 mg Ixekizumab Q4W | Percentage of Participants Achieving PASI 100 | 43.5 Percentage of participants |
| 80 mg Ixekizumab Q4W/Q2W | Percentage of Participants Achieving PASI 100 | 49.3 Percentage of participants |
| 80 mg Ixekizumab Q2W | Percentage of Participants Achieving PASI 100 | 59.7 Percentage of participants |
Secondary
Percentage of Participants Achieving PASI 90
PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no Ps to 72 for the most severe disease. For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region \* area score \* weighing factor \[head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)\]. Overall scores range from 0 (no Ps) to 72 (the most severe disease).
Time frame: Week 52
Population: All randomized participants analyzed according to the treatment to which they were assigned. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 80 mg Ixekizumab Q4W | Percentage of Participants Achieving PASI 90 | 65.2 Percentage of participants |
| 80 mg Ixekizumab Q4W/Q2W | Percentage of Participants Achieving PASI 90 | 73.9 Percentage of participants |
| 80 mg Ixekizumab Q2W | Percentage of Participants Achieving PASI 90 | 79.5 Percentage of participants |
Secondary
Percentage of Participants Achieving sPGA (0)
The sPGA is the physician's determination of the participant's Ps lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participant's Ps was assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe). An sPGA responder was defined as having a post-baseline sPGA score of 0 or 1 with at least a 2-point improvement from baseline. Participants who did not meet the clinical response criteria or had missing data at Week 52 were considered non-responders for Non-Responder Imputation (NRI) analysis.
Time frame: Week 52
Population: All randomized participants analyzed according to the treatment to which they were assigned. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 80 mg Ixekizumab Q4W | Percentage of Participants Achieving sPGA (0) | 44.8 Percentage of participants |
| 80 mg Ixekizumab Q4W/Q2W | Percentage of Participants Achieving sPGA (0) | 48.7 Percentage of participants |
| 80 mg Ixekizumab Q2W | Percentage of Participants Achieving sPGA (0) | 60.1 Percentage of participants |
Secondary
Percent Improvement in PASI
The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no Ps to 72 for the most severe disease. Least Squares mean (LSmean) was calculated using Mixed-Effects Model of Repeated Measures (MMRM) analysis including dosing regimen, country, baseline weight category, baseline value, visit, dosing regimen-by-visit, and baseline value-by-visit interactions as fixed factors, with variance-covariance structure set to unstructured.
Time frame: Baseline, Week 52
Population: All randomized participants analyzed according to the treatment to which they were assigned and had a baseline and post-baseline measurement for PASI. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg Ixekizumab Q4W | Percent Improvement in PASI | 91.09 Percent change | Standard Error 0.89 |
| 80 mg Ixekizumab Q4W/Q2W | Percent Improvement in PASI | 94.24 Percent change | Standard Error 0.9 |
| 80 mg Ixekizumab Q2W | Percent Improvement in PASI | 96.25 Percent change | Standard Error 0.71 |
Secondary
Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough,ss) of Ixekizumab
Trough concentrations at steady state of Ixekizumab were evaluated.
Time frame: Predose, Week 4, 12, 24, 36 and 52 Post dose
Population: All randomized participants analyzed according to treatment to which they were assigned with evaluable PK samples that met the definition of being a trough concentration. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 80 mg Ixekizumab Q4W | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough,ss) of Ixekizumab | Week 36 | 2.83 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 74 |
| 80 mg Ixekizumab Q4W | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough,ss) of Ixekizumab | Week 12 | 2.72 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 72 |
| 80 mg Ixekizumab Q4W | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough,ss) of Ixekizumab | Week 52 | 2.43 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 79 |
| 80 mg Ixekizumab Q4W | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough,ss) of Ixekizumab | Week 24 | 2.65 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 73 |
| 80 mg Ixekizumab Q4W | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough,ss) of Ixekizumab | Week 4 | 3.55 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 76 |
| 80 mg Ixekizumab Q4W/Q2W | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough,ss) of Ixekizumab | Week 24 | 2.71 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 85 |
| 80 mg Ixekizumab Q4W/Q2W | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough,ss) of Ixekizumab | Week 36 | 2.88 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 73 |
| 80 mg Ixekizumab Q4W/Q2W | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough,ss) of Ixekizumab | Week 52 | 2.77 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 73 |
| 80 mg Ixekizumab Q4W/Q2W | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough,ss) of Ixekizumab | Week 12 | 2.81 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 80 |
| 80 mg Ixekizumab Q4W/Q2W | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough,ss) of Ixekizumab | Week 4 | 4.03 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 72 |
| 80 mg Ixekizumab Q2W | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough,ss) of Ixekizumab | Week 24 | 3.48 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 78 |
| 80 mg Ixekizumab Q2W | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough,ss) of Ixekizumab | Week 4 | 2.78 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 67 |
| 80 mg Ixekizumab Q2W | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough,ss) of Ixekizumab | Week 12 | 1.95 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 70 |
| 80 mg Ixekizumab Q2W | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough,ss) of Ixekizumab | Week 36 | 5.76 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 67 |
| 80 mg Ixekizumab Q2W | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough,ss) of Ixekizumab | Week 52 | 5.73 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 68 |
| 80 mg Ixekizumab Q2W Continuous | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough,ss) of Ixekizumab | Week 36 | 7.73 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 76 |
| 80 mg Ixekizumab Q2W Continuous | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough,ss) of Ixekizumab | Week 12 | 8.23 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 56 |
| 80 mg Ixekizumab Q2W Continuous | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough,ss) of Ixekizumab | Week 4 | 7.87 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 63 |
| 80 mg Ixekizumab Q2W Continuous | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough,ss) of Ixekizumab | Week 24 | 7.89 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 66 |
| 80 mg Ixekizumab Q2W Continuous | Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough,ss) of Ixekizumab | Week 52 | 6.96 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 87 |