A Study Comparing Different Dosing Regimens of Ixekizumab (LY2439821) in Participants With Moderate to Severe Plaque Psoriasis

Phase 3

Completed

Conditions: Plaque Psoriasis

Interventions: Drug: Ixekizumab
Drug: Placebo

Registration Number: NCT02513550

Lead Sponsor: Eli Lilly and Company

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1257

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
80 mg Ixekizumab Q4W	Placebo	160 mg ixekizumab given as 2 SQ injections at baseline and then 80 mg ixekizumab given as 1 SQ injection every 4 weeks (Q4W) to week 52. Placebo administered SQ, Q2W to maintain blind.
80 mg Ixekizumab Q4W/Q2W Maximum Extended Enrollment Cohort	Placebo	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.
80 mg Ixekizumab Q2W	Placebo	160 milligrams (mg) ixekizumab given as 2 subcutaneous (SQ) injections at baseline and then 80 mg ixekizumab given as 1 SQ injection every 2 weeks (Q2W) to week 52. Placebo administered SQ, Q2W to maintain blind.
80 mg Ixekizumab Q4W/Q2W	Placebo	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.
80 mg Ixekizumab Q2W Maximum Extended Enrollment (ME2) Cohort	Placebo	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.
80 mg Ixekizumab Q4W Maximum Extended Enrollment Cohort	Placebo	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.
80 mg Ixekizumab Q2W	Ixekizumab	160 milligrams (mg) ixekizumab given as 2 subcutaneous (SQ) injections at baseline and then 80 mg ixekizumab given as 1 SQ injection every 2 weeks (Q2W) to week 52. Placebo administered SQ, Q2W to maintain blind.
80 mg Ixekizumab Q4W	Ixekizumab	160 mg ixekizumab given as 2 SQ injections at baseline and then 80 mg ixekizumab given as 1 SQ injection every 4 weeks (Q4W) to week 52. Placebo administered SQ, Q2W to maintain blind.
80 mg Ixekizumab Q4W/Q2W	Ixekizumab	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.
80 mg Ixekizumab Q2W Maximum Extended Enrollment (ME2) Cohort	Ixekizumab	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.
80 mg Ixekizumab Q4W Maximum Extended Enrollment Cohort	Ixekizumab	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.
80 mg Ixekizumab Q4W/Q2W Maximum Extended Enrollment Cohort	Ixekizumab	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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).
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.
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.
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.
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.
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.
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.
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.
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.
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 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).
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 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.

Trial Locations

Locations (62): David Stoll, M.D.
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Beverly Hills, California, United States
Anaheim Clinical Trials, LLC
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Anaheim, California, United States
Dermatology Research Associates
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Los Angeles, California, United States
Clinical Science Institute
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Santa Monica, California, United States
Florida Academic Dermatology Centers
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Coral Gables, Florida, United States
Renstar Medical Research
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Ocala, Florida, United States
Avail Clinical Research LLC
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DeLand, Florida, United States
Jacksonville Center for Clinical Research
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Jacksonville, Florida, United States
Ameriderm Research
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Ormond Beach, Florida, United States
University Dermatology
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Darien, Illinois, United States
Deaconess Clinic Inc
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Evansville, Indiana, United States
The South Bend Clinic
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South Bend, Indiana, United States
Kansas City Dermatology, PA
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Overland Park, Kansas, United States
Dr. Shondra Smith MD
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Lake Charles, Louisiana, United States
DermAssociates, P.C.
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Rockville, Maryland, United States
ActivMed Practices & Research, Inc
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Newington, New Hampshire, United States
Central Dermatology PC
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Saint Louis, Missouri, United States
Psoriasis Treatment Center of Central New Jersey
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East Windsor, New Jersey, United States
Academic Dermatology Associates
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Albuquerque, New Mexico, United States
Mount Sinai School of Medicine Dermatology Clinical Trials
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New York, New York, United States
Skin Search of Rochester, Inc
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Rochester, New York, United States
PMG Research of Wilmington, LLC
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Wilmington, North Carolina, United States
Wilmington Dermatology Center
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Wilmington, North Carolina, United States
Healthcare Research Consultant
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Tulsa, Oklahoma, United States
Oregon Dermatology and Research Center
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Portland, Oregon, United States
Dermatology and Skin Surgery Center
🇺🇸
Exton, Pennsylvania, United States
Pennsylvania Regional Center for Arthritis & Osteoarthritis
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Wyomissing, Pennsylvania, United States
Yardley Dermatology
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Yardley, Pennsylvania, United States
Clinical Partners LLC
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Johnston, Rhode Island, United States
Coastal Carolina Research Center, Inc.
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Mount Pleasant, South Carolina, United States
The Skin Wellness Center PC
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Knoxville, Tennessee, United States
Center for Clinical Studies
🇺🇸
Webster, Texas, United States
Pflugerville Dermatology Clinical Research Center
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Pflugerville, Texas, United States
Virginia Clinical Research
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Norfolk, Virginia, United States
Multicare Health System
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Tacoma, Washington, United States
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.
🇨🇳
Taipei, Taiwan
Office of Dr. Samuel Sanchez PSC
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Caguas, Puerto Rico
Office of Dr. Alma M. Cruz
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Carolina, Puerto Rico
Ponce School of Medicine CAIMED Center
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Ponce, Puerto Rico
GCM Medical Group PSC
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San Juan, Puerto Rico
Mindful Medical Research
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San Juan, Puerto Rico
Advanced Medical Research
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Atlanta, Georgia, United States
Menter Dermatology Research Institute
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Dallas, Texas, United States
Wenatchee Valley Hospital & Clinics
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Wenatchee, Washington, United States
University of Pittsburgh Medical Center
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Pittsburgh, Pennsylvania, United States
University Hospitals of Cleveland
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Cleveland, Ohio, United States
Medical Center for Clinical Research
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San Diego, California, United States
University Clinical Trials, Inc.
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San Diego, California, United States
Dawes Fretzin Clinical Research
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Indianapolis, Indiana, United States
Clinical Trials of Texas, Inc.
🇺🇸
San Antonio, Texas, United States
Dermatology Associates
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Seattle, Washington, United States
Heartland Research Associates
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Wichita, Kansas, United States
Center for Dermatology and Laser Surgery
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Sacramento, California, United States
University of South Florida
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Tampa, Florida, United States
Total Skin and Beauty Dermatology Center PC
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Birmingham, Alabama, United States
Cherry Creek Research, Inc
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Denver, Colorado, United States
Dermatology Specialist
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Louisville, Kentucky, United States
University of North Carolina Dermatology and Skin Cancer Center
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Chapel Hill, North Carolina, United States
Piedmont Medical Research
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Winston-Salem, North Carolina, United States
Oregon Medical Research Center
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Portland, Oregon, United States
Austin Dermatology Associates
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Austin, Texas, United States
University of Utah Medical Center
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Salt Lake City, Utah, United States