A Phase 3 Study in Participants With Moderate to Severe Psoriasis (UNCOVER-1)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01474512
First received: November 15, 2011
Last updated: April 20, 2016
Last verified: April 2016

November 15, 2011
April 20, 2016
November 2011
June 2014   (final data collection date for primary outcome measure)
  • Percentage of Participants With Static Physician Global Assessment (sPGA) of 0 or 1 (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Ps Measure: sPGA) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    The sPGA is the physician's determination of the participant's Ps lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participants Ps were assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe). An sPGA responder was defined as having a post-baseline sPGA score of "0" or "1" with at least a 2-point improvement from baseline.
  • Percentage of Participants Achieving ≥75% Improvement in Ps Area and Severity Index (PASI75) (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Psoriasis Measure: PASI) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no Ps) to 72 (the most severe disease). Participants achieving PASI75 were defined as having an improvement of ≥75% in the PASI score compared to baseline.
  • Efficacy of LY2439821 in subjects with moderate to severe plaque psoriasis. Measure: Static Physician Global Assessment (sPGA) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Efficacy of LY2439821 in subjects with moderate to severe plaque psoriasis. Measure: Psoriasis Area and Severity Index (PASI) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01474512 on ClinicalTrials.gov Archive Site
  • Percentage of Participants Achieving an sPGA of 0 (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Ps Measure: sPGA) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    The sPGA is the physician's determination of the participant's Ps lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participants Ps were assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe).
  • Percentage of Participants Achieving PASI 90% (PASI90) or 100% (PASI100) (Efficacy of Ixekizumab in Participants With Moderate to Severe Plaque Ps Measure: PASI) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored by itself and the scores were then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor [head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)]. Overall scores range from 0 (no Ps) to 72 (the most severe disease). Participants achieving PASI90 or PASI100 were defined as having an improvement of ≥90% or of 100% respectively in PASI scores compared to baseline.
  • Percentage of Participants Maintaining sPGA 0 or 1 After Re-Randomization at Start of Maintenance Dosing Period [ Time Frame: Week 60 ] [ Designated as safety issue: No ]
    The sPGA is the physician's determination of the participant's Ps lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participants Ps were assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe).
  • Percentage of Participants With Itch Numeric Rating Scale (Itch NRS) Score ≥4 Point Reduction From Baseline [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    The Itch NRS is a participant-administered, 11-point horizontal scale anchored at 0 (no itch) and 10 (worst itch imaginable). Overall severity of a participant's itching from Ps is indicated by circling the number that best describes the worst level of itching in the past 24 hours.
  • Change From Baseline in Dermatology-Specific Quality of Life Index (DLQI) Score [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    DLQI is a participant-administered, 10-question, validated, quality-of-life questionnaire that covers 6 domains, including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include 0 (not at all), 1 (a little), 2 (a lot), and 3 (very much) and unanswered ("not relevant") responses were scored as "0." Total scores range from 0 to 30, with higher score indicating greater quality of life is impairment. A 5-point change from baseline is considered clinically relevant. Least squares (LS) mean change from baseline was calculated using mixed model repeated measures (MMRM).
  • Change From Baseline in Nail Psoriasis Severity Index (NAPSI) [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    The NAPSI is a numeric, reproducible, objective tool for evaluation of fingernail Ps. This scale is used to evaluate the severity of fingernail bed Ps and fingernail matrix Ps by area of involvement in the fingernail unit. The fingernail is divided with imaginary horizontal and longitudinal lines into quadrants. Each fingernail is given a score for fingernail bed Ps 0 (none) to 4 (Ps in 4 quadrants of the fingernail) and fingernail matrix Ps 0 (none) to 4 (Ps in 4 quadrants of the matrix), depending on the presence (score of 1) or absence (score of 0) of any of the features of fingernail bed or matrix Ps in each quadrant. The NAPSI score of a fingernail is the sum of scores in fingernail bed and fingernail matrix from each quadrant (maximum of 8). Each fingernail is evaluated, then the sum of all fingernails equals the total NAPSI score with a range from 0 to 80 with higher scores indicating more severe psoriasis. LS mean change from baseline was calculated using MMRM.
  • Percent of Body Surface Area (BSA) Involvement of Ps [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    BSA is a physician rating of the percentage of involvement of Ps for each participant. BSA is assessed on a continuous scale from 0% (no involvement) to 100% (full involvement), where 1% corresponds to the size of the participants hand (includes the palm, fingers and thumb). Total BSA is the sum of handprints from the affected areas. LS mean change from baseline was calculated using MMRM.
  • Change From Baseline in Psoriasis Scalp Severity Index (PSSI) [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    The PSSI is a physician assessment of erythema, induration and desquamation and percent of scalp that is covered with a scores range from 0 (none) to 4 (very severe). The composite score is derived from the sum of scores for erythema, induration, and desquamation multiplied by the score recorded for the extent of the scalp area involved, 1 (<10%) to 6 (90%-100%) with a total scores range from 0 to 72, with lower scores indicating less severity. LS mean change from baseline was calculated using MMRM.
  • Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) (Quality of Life and Outcome Assessments. Measures: Participant Reported Outcomes [PRO]) [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    WPAI-PSO is a participant administered, 6-item instrument used to assess the impact of Ps on the productivity impairment within the past 7 days. WPAI-PSO has 4 domains: absenteeism, presenteeism (reduced productivity while at work), an overall work impairment score, and impairment in daily activities performed outside of work. Four scores are derived as percentages: absenteeism, presenteeism (reduced productivity while at work), overall work impairment (absenteeism and presenteeism), and impairment in activities performed outside of work. Percentage is calculated as: each score * 100 with greater scores indicating greater impairment. LS mean change from baseline was calculated using analysis of covariance (ANCOVA).
  • Change From Baseline in Quick Inventory of Depressive Symptomatology-Self Reported 16 Items (QIDS-SR16) [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    QIDS-SR16 is a participant-administered, 16-item instrument intended to assess the existence and severity of symptoms of depression. A participant is asked to consider each statement as it relates to the way they have felt for the past 7 days and rate each on a 4-point scale: 0 (best) to 3 (worst). The sum of the 16 items corresponding to 9 depression domains [sad mood, concentration, self-criticism, suicidal ideation, interest, energy/fatigue, sleep disturbance (initial, middle and late insomnia or hypersomnia), decrease/increase in appetite/weight, and psychomotor agitation/retardation] to give a single total scores range from 0 to 27, with higher scores indicating greater symptom severity. LS mean change from baseline was calculated using ANCOVA.
  • Change From Baseline in Medical Outcomes Study 36-item Short Form Health Survey (SF-36) and Physical Component Summary (PCS) and Mental Component Summary (MCS) [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    The SF-36 is a self-reported instrument that measures the participant's health status during the previous 7 days. It comprises 36-items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. The 8 domains are regrouped in the PCS and MCS scores. Scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. LS mean change from baseline was calculated using ANCOVA.
  • Change From Baseline in Patient's Global Assessment of Disease Severity (PatGA) [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    The PatGA is a single-item self-reported instrument asking the participant to rate the severity of their psoriasis "today" by circling a number on the numeric rating scale from 0 (Clear = no psoriasis) to 5 (Severe = the worst their psoriasis has ever been). LS mean change from baseline calculated using MMRM.
  • Percentage of Participants Achieving Palmoplantar PASI (PPASI) of ≥50% (PPASI50), ≥75% (PPASI75), or 100% (PPASI100) Improvement [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    The Palmoplantar PASI is a composite score derived from the sum of scores for erythema, induration, and desquamation [scores range from 0 (none) to 4 (very severe) for each] multiplied by the score for the extent of palm and sole area involvement [scores range from 0 (0%) to 6 (90 to100%)], with a total scores range from 0 to 72. Participants achieving PPASI50, PPASI75 or PASI100 were defined as having an improvement of at least 50%, 90%, or of 100%, respectively, in the PPASI scores compared to baseline.
  • Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough ss) [ Time Frame: Weeks 12 and 24 ] [ Designated as safety issue: No ]
  • Percentage of Participants With Anti-ixekizumab Antibodies [ Time Frame: Baseline through Week 12 ] [ Designated as safety issue: No ]
    Percentage of participants with treatment-emergent positive anti-ixekizumab antibodies was summarized by treatment group. Percentage was calculated based on the number of evaluable participants and was calculated by number of participants with treatment-emergent positive anti-ixekizumab antibodies / number of evaluable participants * 100%.
  • Efficacy of LY2439821 in subjects with moderate to severe plaque psoriasis. Measure: Static Physician Global Assessment (sPGA) [ Time Frame: Baseline through Week 60 ] [ Designated as safety issue: No ]
  • Efficacy of LY2439821 in subjects with moderate to severe plaque psoriasis. Measure: Psoriasis Area and Severity Index (PASI) [ Time Frame: Baseline through Week 60 ] [ Designated as safety issue: No ]
  • Quality of life and outcome assessments. Measures: Patient Reported Outcomes (PRO) [ Time Frame: Baseline through Week 60 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Phase 3 Study in Participants With Moderate to Severe Psoriasis
A Multicenter Study With a Randomized, Double-Blind, Placebo-Controlled Induction Dosing Period Followed by a Randomized Maintenance Dosing Period and a Long- Term Extension Period to Evaluate the Efficacy and Safety of LY2439821 in Patients With Moderate-to-Severe Plaque Psoriasis
This study will assess the safety and efficacy of LY2439821 compared to placebo in participants with moderate to severe, chronic plaque psoriasis.
Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Psoriasis
  • Drug: 80 mg Ixekizumab Dosing Regimens 1, 2, and 3
    Administered SC
    Other Name: LY2439821
  • Drug: Placebo
    Administered SC
  • Experimental: 80 milligrams (mg) Ixekizumab Dosing Regimen 1 (Q2W)
    Administered as two 80-mg subcutaneous (SC) injections at Week 0, then one 80-mg SC injection per Dosing Regimen 1 [every 2 weeks (Q2W)] up to and including Week 10. At Week 12, arm is re-randomized to placebo, Dosing Regimen 2 [every 4 weeks (Q4W)] or Dosing Regimen 3 [every 12 weeks Q12W)].
    Intervention: Drug: 80 mg Ixekizumab Dosing Regimens 1, 2, and 3
  • Experimental: 80 mg Ixekizumab Dosing Regimen 2 (Q4W)
    Administered as two 80-mg SC injections at Week 0, then one 80-mg SC injection per Dosing Regimen 2 (Q4W) up to and including Week 10. At Week 12, arm is re-randomized to placebo, Dosing Regimen 2 (Q4W) or Dosing Regimen 3 (Q12W).
    Intervention: Drug: 80 mg Ixekizumab Dosing Regimens 1, 2, and 3
  • Experimental: 80 mg Ixekizumab Dosing Regimen 3 (Q12W)
    Dosing Regimen 3 (Q12W) is not used until Week 12. At Week 12, participants who were re-randomized to this arm were administered one 80-mg SC injection Q12W.
    Intervention: Drug: 80 mg Ixekizumab Dosing Regimens 1, 2, and 3
  • Placebo Comparator: Placebo
    Administered as 2 SC injections at Week 0, then 1 SC injection per Dosing Regimen 1 (Q2W) up to and including Week 10. At Week 12, arm is re-randomized to placebo or Dosing Regimen 2 (Q4W).
    Intervention: Drug: Placebo
Gordon KB, Blauvelt A, Papp KA, Langley RG, Luger T, Ohtsuki M, Reich K, Amato D, Ball SG, Braun DK, Cameron GS, Erickson J, Konrad RJ, Muram TM, Nickoloff BJ, Osuntokun OO, Secrest RJ, Zhao F, Mallbris L, Leonardi CL; UNCOVER-1 Study Group; UNCOVER-2 Study Group; UNCOVER-3 Study Group. Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque Psoriasis. N Engl J Med. 2016 Jul 28;375(4):345-56. doi: 10.1056/NEJMoa1512711. Epub 2016 Jun 8.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
1296
November 2018
June 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Present with chronic plaque psoriasis based on a confirmed diagnosis of chronic psoriasis vulgaris for at least 6 months prior to randomization
  • At least 10% Body Surface Area (BSA) of Psoriasis at screening and at randomization
  • Static Physician Global Assessment (sPGA) score of at least 3 and Psoriasis Area and Severity Index (PASI) score of at least 12 at screening and at randomization
  • Candidate for phototherapy and/or systemic therapy
  • Men must agree to use a reliable method of birth control during the study
  • Women must agree to use birth control or remain abstinent during the study and for at least 12 weeks after stopping treatment

Exclusion Criteria:

  • Pustular, erythrodermic, and/or guttate forms of psoriasis
  • History of drug-induced psoriasis
  • Clinically significant flare of psoriasis during the 12 weeks prior to randomization
  • Concurrent or recent use of any biologic agent
  • Received systemic psoriasis therapy [such as psoralen and ultraviolet A (PUVA) light therapy] or phototherapy within the previous 4 weeks; or had topical psoriasis treatment within the previous 2 weeks prior to randomization
  • Cannot avoid excessive sun exposure or use of tanning booths for at least 4 weeks prior to randomization and during the study
  • Have participated in any study with interleukin (IL)-17 antagonists, including LY2439821
  • Serious disorder or illness other than plaque psoriasis
  • Serious infection within the last 3 months
  • Breastfeeding or nursing (lactating) women.
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada,   Denmark,   Germany,   Hungary,   Italy,   Japan,   Poland,   Romania,   United Kingdom
 
NCT01474512
12972, I1F-MC-RHAZ
Yes
Not Provided
Not Provided
Eli Lilly and Company
Eli Lilly and Company
Not Provided
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
Eli Lilly and Company
April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP