A Multicenter, Randomized, Double-Blind Study Comparing the Efficacy and Safety of Ixekizumab Dosing Regimens in Patients With Moderate-to-Severe Plaque Psoriasis
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Eli Lilly and Company
- Enrollment
- 1,257
- Locations
- 62
- Primary Endpoint
- Percentage of Participants Achieving Static Physician Global Assessment (sPGA) of (0,1)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts 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
Arms & Interventions
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.
Intervention: Placebo (Drug)
80 mg Ixekizumab Q2W
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.
Intervention: Ixekizumab (Drug)
80 mg Ixekizumab Q2W
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.
Intervention: Placebo (Drug)
80 mg Ixekizumab Q4W
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.
Intervention: Ixekizumab (Drug)
80 mg Ixekizumab Q4W
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.
Intervention: Placebo (Drug)
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.
Intervention: Ixekizumab (Drug)
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.
Intervention: Placebo (Drug)
80 mg Ixekizumab Q2W Maximum Extended Enrollment (ME2) 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.
Intervention: Ixekizumab (Drug)
80 mg Ixekizumab Q2W Maximum Extended Enrollment (ME2) 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.
Intervention: Placebo (Drug)
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.
Intervention: Ixekizumab (Drug)
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.
Intervention: Placebo (Drug)
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.
Intervention: Ixekizumab (Drug)
Outcomes
Primary Outcomes
Percentage of Participants Achieving Static Physician Global Assessment (sPGA) of (0,1)
Time Frame: 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)
Time Frame: 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 Outcomes
- Percentage of Participants Achieving PASI 90(Week 52)
- Change From Baseline in Itch NRS Score(Baseline, Week 52)
- Change From Baseline in Skin Pain Visual Analog Scale (VAS)(Baseline, Week 52)
- Change From Baseline in European Quality of Life - 5 Dimensions 5 Level (EQ-5D-5L) VAS(Baseline, Week 52)
- Mean Change From Baseline in Nail Psoriasis Severity Index (NAPSI) Score(Baseline, Week 52)
- Mean Change From Baseline in Psoriasis Scalp Severity Index (PSSI) Score(Baseline, Week 52)
- Percentage of Participants Achieving Dermatology Life Quality Index (DLQI) Total Score of 0 and 1 (DLQI [0,1])(Week 52)
- Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough,ss) of Ixekizumab(Predose, Week 4, 12, 24, 36 and 52 Post dose)
- Number of Participants With Anti-Ixekizumab Antibodies(Baseline through Week 52)
- Change From Baseline in PASI(Baseline, Week 52)
- Mean Change From Baseline in Percent Body Surface Area (BSA) Involvement(Baseline, Week 52)
- Percentage of Participants Achieving an Itch Numeric Rating Scale (Itch NRS) ≥4 Point Reduction From Baseline(Baseline, Week 52)
- Change From Baseline in DLQI Total Score(Baseline, Week 52)
- Percentage of Participants Achieving sPGA (0)(Week 52)
- Percentage of Participants Achieving PASI 100(Week 52)
- Percent Improvement in PASI(Baseline, Week 52)
- Mean Change From Baseline in Palmoplantar PASI (PPASI)(Baseline, Week 52)