A Study of Ixekizumab (LY2439821) in Participants With Moderate-to-Severe Plaque Psoriasis Naive to Systemic Treatment

Phase 3

Completed

• Conditions: Plaque Psoriasis
• Interventions: Drug: Fumaric Acid Esters; Drug: Ixekizumab; Drug: Methotrexate

• Registration Number: NCT02634801
• Lead Sponsor: Eli Lilly and Company

Brief Summary

The main purpose of this study is to evaluate the efficacy of ixekizumab compared to fumaric acid esters (FAE) and methotrexate (MTX) in participants with moderate-to-severe plaque psoriasis who are naive to systemic treatment.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-12-16
• Study First Submitted QC: 2015-12-16
• Study First Posted: 2015-12-18
• Study Start: 2016-01-20
• Primary Completion: 2016-11-29
• Study Completion: 2017-11-14
• Results First Submitted: 2017-11-27
• Results First Submitted QC: 2018-06-21
• Results First Posted: 2018-07-18
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-25
• Last Update Posted: 2019-10-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 162

Inclusion Criteria

• Present with moderate-to-severe chronic plaque psoriasis based on a diagnosis of chronic psoriasis for at least 6 months before baseline.
• Participants who are candidates for systemic therapy and who are naive to systemic treatment for psoriasis.
• Have a (PASI score >10 or BSA >10) and DLQI >10 at screening and at baseline.

Exclusion Criteria

• Have predominant pattern of pustular, erythrodermic, and/or guttate forms of psoriasis.
• Have received systemic nonbiologic psoriasis therapy.
• Have prior, concurrent, or recent use of ixekizumab or any other biological psoriasis therapy.
• Have any condition or contraindication as addressed in the local labeling for MTX or FAE.
• Presence of significant uncontrolled cerebro-cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, neurologic, or neuropsychiatric disorders or abnormal laboratory values at screening.
• Have severe gastrointestinal disease, oral ulcer, or known, active gastrointestinal ulcer.
• Have had a serious infection or are immunocompromised.
• At screening, participants with significant, present, or early liver disease, e.g., explained by alcohol consumption or hepatic insufficiency.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fumaric Acid Esters	Fumaric Acid Esters	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Ixekizumab	Ixekizumab	160 milligrams (mg) ixekizumab given as two subcutaneous injections (SC) followed by 80 mg ixekizumab given SC every 2 weeks until week 12 and then 80 mg ixekizumab given SC every 4 weeks until week 24. Extension Period: At week 24, participants have the option to continue ixekizumab treatment for up to 36 weeks.
Fumaric Acid Esters	Ixekizumab	Starting dose of 105 mg FAE given orally followed by 215 mg FAE given orally 1 to 3 times per day until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Methotrexate	Methotrexate	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.
Methotrexate	Ixekizumab	7.5 mg starting dose up to 30 mg MTX given orally once a week until week 24. Extension Period: At week 24, participants have the option to begin ixekizumab treatment for up to 36 weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With a ≥75% Improvement in Psoriasis Area and Severity Index (PASI 75) at Week 24	Week 24	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).

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in PASI Total Score	Baseline, Week 24	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). LS mean change from baseline in PASI was calculated using Analysis of Covariance (ANCOVA) with modified Baseline- Observation- Carried Forward (mBOCF) and with terms for baseline and treatment.
Change From Baseline on Dermatology Life Quality Index (DLQI) Total Score	Baseline, Week 24	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), and a 5-point change from baseline is considered clinically relevant. LS mean change from baseline in DLQI was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Change From Baseline on Itch Numeric Rating Scale (NRS) Score	Baseline, Week 24	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 psoriasis (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 was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Percentage of Participants With a ≥90% Improvement in Psoriasis Area and Severity Index (PASI 90) From Baseline	Week 24	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).
Change From Baseline in Psoriasis Scalp Severity Index (PSSI) Total Score	Baseline, Week 24	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 from baseline in PSSI was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Patient Benefit Index (PBI) Overall Benefit Score	Week 24	The PBI assessment consists of 2 steps: before treatment, every patient defines his/her treatment needs according to a standardized list (Patient Needs Questionnaire \[PNQ\]). After treatment, the patient rates the degree of benefits achieved (Patient Benefits Questionnaire \[PBQ\]). 25 items are rated on a 5-point scale with values from 0 (not at all) to 4 (very), allowing for "did not apply to me" (5) and missing.; For each treatment goal the PNQ importance is derived by dividing the respective PNQ item by the sum of all PNQ items. The weighted sum of each PBQ item with its respective PNQ importance yields the PBI score.; LS mean was calculated using ANCOVA with LOCF and with a term for treatment.
Change From Baseline on the Skin Pain Visual Analog Scale (VAS)	Baseline, Week 24	The pain VAS is a participant-administered single-item scale designed to measure Skin pain from Psoriasis using a 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 pain) to 100 mm (pain as severe as you can imagine).; LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Percentage of Participants With a 100% Improvement in Psoriasis Area and Severity Index (PASI 100) From Baseline	Week 24	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).
Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis	Baseline, Week 24	The percentage involvement of psoriasis on each participant's body surface area 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 change from baseline in BSA was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Change From Baseline in Palmoplantar Psoriasis Severity Index (PPASI) Total Score	Baseline, Week 24	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 change from baseline in PPASI was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS)	Baseline, Week 24	The SF-36 is a participant-reported outcome measure evaluating participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. The 8 domains are regrouped into the PCS and MCS scores. The summary scores range from 0 to 100, lower scores = more disability, higher scores = less disability and better health. In this study, the SF-36 acute version was used, which has a 1-week recall period.; LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Percentage of Participants With a Static Physician Global Assessment (sPGA) (0,1) and ≥2 Point Improvement From Baseline Among Those With sPGA Score ≥3 at Baseline	Week 24	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. 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 DLQI (0,1)	Week 24	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), and a 5-point change from baseline is considered clinically relevant.
Change From Baseline on Patient's Global Assessment (PatGA) of Disease Severity	Baseline, Week 24	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 was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Change From Baseline on the Psoriasis Skin Appearance Bothersomeness (PSAB) Total Score	Baseline, Week 24	PSAB measure is a 3-item scale designed to measure the degree of bothersomeness of skin appearance due to Ps in participants with Ps. Participants are asked to indicate on 3 numeric rating scales (NRS) from 0 (not at all bothered) to 10 (extremely bothered) how bothered they are by any redness or discoloration, thickness, and scaling or flaking on their skin due to Ps.; The scores from the 3 NRS items are summed for a total score ranging from 0 to 30, where 0 indicating no bothersomeness and 30 indicating greater bothersomeness.; LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Change From Baseline on Quick Inventory of Depressive Symptomatology-Self Report (16 Items) (QIDS-SR16)	Baseline, Week 24	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. Whereas 0-5 indicates no symptoms.; LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Change From Baseline in 36-Item Short Form Health Survey (SF-36) Mental Component Summary (MCS) Scores	Baseline, Week 24	The SF-36 is a participant-reported outcome measure evaluating participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. The 8 domains are regrouped into the PCS and MCS scores. The summary scores range from 0 to 100, lower scores = more disability, higher scores = less disability and better health. In this study, the SF-36 acute version was used, which has a 1-week recall period.; LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Change From Baseline on the Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA-CLIN) Total Score	Baseline, Week 24	NAPPA is a clinical and participant-reported outcomes tool, and consists of 3 components: a questionnaire assessing nail-specific quality of life NAPPA-QoL (Nail Assessment in Psoriasis and Psoriatic Arthritis Quality of Life), a 2-part questionnaire assessing participant relevant needs and treatment benefits NAPPA-PBI (Nail Assessment in Psoriasis and Psoriatic Arthritis - Patient Benefit Index), and a clinical assessment of objective finger nail psoriasis severity NAPPA-CLIN.; Sum of all assessed finger and toes ranging between 0 (no involvement) to 16 (worst involvement).; LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Change From Baseline in European Quality of Life - 5 Dimensions 5 Level (EQ-5D 5L) "Bolt On" - Psoriasis (PSO) Index Score	Baseline, Week 24	The European Quality of Life - 5 Dimensions 5 Level (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 a descriptive system of the respondent's health which comprises the following 5 dimensions: 1) mobility 2) self-care 3) usual activities 4) pain/discomfort 5) anxiety/depression. The Bolt On PSO is an addition to the EQ-5D-5L that consists of 2 dimensions specific to psoriatic disease: 6) skin irritation (itching) and 7) self-confidence. Index scores for the Bolt On PSO range from 0.0042 to 1.0 (worse to better health).; LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Change From Baseline in European Quality of Life - 5 Dimensions 5 Level (EQ-5D) + Bolt On UK Population-based Index Score	Baseline, Week 24	The European Quality of Life - 5 Dimensions 5 Level (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 a descriptive system of the respondent's health which comprises the following 5 dimensions: 1) mobility 2) self-care 3) usual activities 4) pain/discomfort 5) anxiety/depression. The EQ-5D-5L health states were converted into a single summary index by applying a crosswalk using a United Kingdom (UK) Population value set to each of the levels in each dimension. This produced participant-level index scores between -0.594 and 1.0 (worse to better health).; LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Change From Baseline in European Quality of Life - 5 Dimensions 5 Level (EQ-5D 5L) "Bolt On" - Visual Analog Scale Score	Baseline, Week 24	The EQ-5D 5L is a standardized measure of health status that includes a descriptive system of the respondent's health and a rating of his/her current health state using a 0 (worst health imaginable)- to 100 (best health imaginable)-millimeter (mm) Visual Analog Scale (VAS).; LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Percentage of Participants With Positive Responses to Neck/Face Psoriasis Question	Week 24	Studying psoriasis involvement in the face, neck, and the genitals is of considerable interest for participants. These are locations that bear high potential for stigmatization and/or psychological distress, and, hence, effects in those regions are assumed to heavily influence participant's quality of life.; Following set of binary questions were asked to check the satisfaction of participants.; 1. Does the participant currently have visible psoriasis on face/neck? (Yes/No); 2. Does the participant currently have psoriasis on the genital area? (Yes/No)
Percentage of Participants Positive Responses to Genital Psoriasis Question	Week 24	Studying psoriasis involvement in the face, neck, and the genitals is of considerable interest for participants. These are locations that bear high potential for stigmatization and/or psychological distress, and, hence, effects in those regions are assumed to heavily influence participant's quality of life.; Following set of binary questions were asked to check the satisfaction of participants.; 1. Does the patient currently have visible psoriasis on face/neck? (Yes/No); 2. Does the patient currently have psoriasis on the genital area? (Yes/No) The genital area includes the labia majora (hair-bearing), labia minora modified mucus membrane, and perineum in female patients; and the penis glans, penis - shaft, and scrotum in male patients.
Change From Baseline on the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO), Absenteeism Score	Baseline, Week 24	The WPAI-PSO consists of 6 questions to determine employment status, hours missed from work because of psoriasis, hours missed from work for other reasons, hours actually worked, the degree to which psoriasis affected work productivity while at work, and the degree to which psoriasis affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Each WPAI score is expressed as impairment percentages (0-100), where 0 (no impairement) and 100 (greater impairment).; LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Change From Baseline on the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO), Presenteeism Score	Baseline, Week 24	The WPAI-PSO consists of 6 questions to determine employment status, hours missed from work because of psoriasis, hours missed from work for other reasons, hours actually worked, the degree to which psoriasis affected work productivity while at work, and the degree to which psoriasis affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Each WPAI score is expressed as impairment percentages (0-100), where 0 (no impairement) and 100 (greater impairment).; LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Change From Baseline on the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO), Impairment in Activities Performed Outside of Work	Baseline, Week 24	The WPAI-PSO consists of 6 questions to determine employment status, hours missed from work because of psoriasis, hours missed from work for other reasons, hours actually worked, the degree to which psoriasis affected work productivity while at work, and the degree to which psoriasis affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Each WPAI score is expressed as impairment percentages (0-100), where 0 (no impairement) and 100 (greater impairment).; LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Change From Baseline on the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO), Overall Work Impairment Score	Baseline, Week 24	The WPAI-PSO consists of 6 questions to determine employment status, hours missed from work because of psoriasis, hours missed from work for other reasons, hours actually worked, the degree to which psoriasis affected work productivity while at work, and the degree to which psoriasis affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Each WPAI score is expressed as impairment percentages (0-100), where 0 (no impairement) and 100 (greater impairment).; LS mean change from baseline was calculated using ANCOVA with mBOCF and with terms for baseline and treatment.
Mean Adherence on Medication and Satisfaction With Therapy (STAQ)	Week 24	Systemic Therapy Adherence Questionnaire (STAQ) is a 38 item questionnaire that was developed by shortening and adapting the Topical Treatment Adherence Questionnaire (TTAQ) for administration to participants under systemic therapy. The following STAQ items are of special interest for this study.; 1. STAQ item 13 (The treatment does not affect my sex life); 2. STAQ item 16 (I am enjoying life again as a result of the treatment); 3. STAQ item 20 (The side effects of the treatment were acceptable); 4. STAQ item 31 (I am satisfied with the efficacy of the treatment); 5. STAQ item 32 (I am satisfied with the tolerability of the treatment); 6. STAQ item 35 (The positive aspects of the treatment outweigh the negative ones).; The STAQ items are on a 4-point Likert scale with scores between 0 (strong disagreement) and 3 (strong agreement). LS mean was calculated using ANCOVA with term for treatment.

Trial Locations

Locations (2)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.; 🇩🇪 Ulm, Germany

For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.; 🇩🇪 Kiel, Germany