A Study in Participants With Moderate to Severe Psoriasis (UNCOVER-3) (UNCOVER-3)
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| ClinicalTrials.gov Identifier: NCT01646177 |
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Recruitment Status :
Completed
First Posted : July 20, 2012
Results First Posted : October 21, 2016
Last Update Posted : July 28, 2020
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Sponsor:
Eli Lilly and Company
Information provided by (Responsible Party):
Eli Lilly and Company
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Brief Summary:
This study will assess the safety and efficacy of ixekizumab (LY2439821), compared to etanercept and placebo in participants with moderate to severe chronic plaque psoriasis.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Psoriasis | Drug: Placebo Drug: 50 mg etanercept Drug: 80 mg ixekizumab | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 1346 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A 12-Week Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Comparing the Efficacy and Safety of LY2439821 to Etanercept and Placebo in Patients With Moderate to Severe Plaque Psoriasis With a Long-Term Extension Period |
| Actual Study Start Date : | July 28, 2012 |
| Actual Primary Completion Date : | May 22, 2014 |
| Actual Study Completion Date : | July 22, 2019 |
| Arm | Intervention/treatment |
|---|---|
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Placebo Comparator: Placebo
Placebo for ixekizumab administered by two SC injections at Week 0, then one SC injection per Dosing Regimen 1 until Week 12. Placebo for etanercept administered by one SC injection twice weekly starting at Week 0 up to Week 12. At Week 12, participants are assigned to Dosing Regimen 2.
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Drug: Placebo
Administered SC |
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Active Comparator: 50 mg etanercept
Administered by SC injections twice weekly starting at Week 0 up to Week 12. At Week 12, arm is assigned to Dosing Regimen 2
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Drug: 50 mg etanercept
Administered SC |
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Experimental: 80 mg ixekizumab Dosing Regimen 2
Administered by two 80 mg SC injections at Week 0, then one 80 mg SC injection per Dosing Regimen 2 until Week 264.
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Drug: 80 mg ixekizumab
Administered SC
Other Name: LY2439821 |
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Experimental: 80 mg ixekizumab Dosing Regimen 1
Administered by two 80 milligram (mg) subcutaneous (SC) injections at Week 0, then one 80 mg SC injection per Dosing Regimen 1 until Week 12. At Week 12, arm is assigned to Dosing Regimen 2.
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Drug: 80 mg ixekizumab
Administered SC
Other Name: LY2439821 |
Primary Outcome Measures :
- Number of Participants Achieving a Static Physician Global Assessment (sPGA) of (0, 1) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: sPGA) [ Time Frame: Week 12 ]The sPGA is a physician's determination of the participant's psoriasis lesions overall at a given time point categorized by descriptions for induration, erythema, and scaling. For the analysis of responses, the participant's psoriasis is assessed as clear (0), minimal (1), mild (2), moderate (3), severe (4), or very severe (5). An sPGA (0,1) response was defined as a post-baseline sPGA score of 0 or 1.
- Number of Participants Achieving Psoriasis Area and Severity Index ≥75% (PASI 75) Improvement (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: PASI) [ Time Frame: Week 12 ]The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation (scaling), erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis to 72 for the most severe disease. Participants achieving PASI 75 was defined as having an improvement of at least 75% in the PASI scores compared to baseline.
Secondary Outcome Measures :
- Number of Participants Achieving an sPGA (0) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: sPGA) [ Time Frame: Week 12 ]The sPGA is a physician's determination of the participant's psoriasis lesions overall at a given time point categorized by descriptions for induration, erythema, and scaling. For the analysis of responses, the participant's psoriasis is assessed as clear (0), minimal (1), mild (2), moderate (3), severe (4), or very severe (5). An sPGA (0) response was defined as a post-baseline sPGA score of 0.
- Number of Participants Achieving ≥90% (PASI 90) Improvement (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: PASI) [ Time Frame: Week 12 ]The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation (scaling), erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis to 72 for the most severe disease. Participants achieving PASI 90 were defined as having an improvement of at least 90% in the PASI scores compared to baseline.
- Number of Participants Achieving 100% (PASI 100) Improvement (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: PASI) [ Time Frame: Week 12 ]The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation (scaling), erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis to 72 for the most severe disease. Participants achieving PASI 100 were defined as having an improvement of at least 100% in the PASI scores compared to baseline.
- Number of Participants Achieving an Itch Numeric Rating Scale (NRS) ≥4 Point Reduction [Quality of Life and Outcome Assessments. Measures: Patient Reported Outcomes (PRO)] [ Time Frame: Week 12 ]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." Participants indicate their overall severity of itching from Psoriasis by circling the number that best describes the worst level of itching in the past 24 hours.
- Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score [ Time Frame: Baseline, Week 12 ]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. Least Square (LS) Means in total DLQI score were calculated using Mixed Model Repeated Measures (MMRM) with baseline score as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects.
- Change From Baseline in Nail Psoriasis Severity Index (NAPSI) Score [ Time Frame: Baseline, Week 12 ]The NAPSI is a numeric, reproducible, objective tool used to evaluate the severity of fingernail bed psoriasis and fingernail matrix psoriasis 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 psoriasis: 0 (none) to 4 (psoriasis in 4 quadrants of the nail) and fingernail matrix psoriasis (0 to 4) depending on the presence (score of 1) or absence (score of 0) of any of the features of fingernail bed and fingernail matrix psoriasis 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, and the sum of all the fingernails is the total NAPSI score (range, 0 to 80). LS Means in NAPSI score were calculated using MMRM with baseline score as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects.
- Percent of Body Surface Area (BSA) Involvement of Psoriasis [ Time Frame: Week 12 ]Percentage involvement of psoriasis on each participants 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 Means in BSA were calculated using MMRM with baseline BSA as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects.
- Change From Baseline in Psoriasis Scalp Severity Index (PSSI) Score [ Time Frame: Baseline, Week 12 ]PSSI is a composite score ranging from 0 (best) to 72 (worst), derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of scalp area involved. LS Means in PSSI score were calculated using MMRM with baseline score as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects.
- Change From Baseline in Quick Inventory of Depressive Symptomatology-Self Report 16 Items (QIDS-SR16) Total Score [Quality of Life and Outcome Assessments. Measures: Patient Reported Outcomes (PRO)] [ Time Frame: Baseline, Week 12 ]The QIDS-SR16 is a self-administered, 16-item instrument in which a participant is asked to consider each statement as it relates to the way they have felt for the past 7 days. There is a 4-point scale for each item ranging from 0 (best) to 3 (worst). The 16 items are scored to give 9 individual 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), which are summed to give a single score ranging from 0 to 27, with higher scores denoting greater symptom severity. LS Means in total QIDS-SR16 score were calculated using the analysis of covariance (ANCOVA) model with treatment, pooled center and baseline QIDS total score.
- Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) [ Time Frame: Baseline, Week 12 ]The WPAI-PSO is a 6-item instrument used to assess the impact of psoriasis on productivity impairment within the past 7 days. It has four 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, overall work impairment (absenteeism and presenteeism), and impairment in activities performed outside of work. Percentage is calculated as: each score * 100 and ranged from 0 to 100. Higher scores indicate greater impairment in productivity. LS Means in each WPAI-PSO score were calculated using the ANCOVA model with treatment, pooled center and baseline WPAI-PSO score.
- Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey, Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores [ Time Frame: Baseline, Week 12 ]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, with higher scores indicating better levels of function and/or better health. In this study, the SF-36 acute version was used, which has a 1 week recall period. LS Means in SF-36 score were calculated using the ANCOVA model with treatment, pooled center and baseline SF-36 score.
- Change From Baseline in Patient's Global Assessment of Disease Severity [ Time Frame: Baseline, Week 12 ]The Patient's Global Assessment of Disease Severity is a single-item participant-reported outcome measure on which participants are asked to rate the severity of their psoriasis "today" from 0 (Clear) = no psoriasis, to 5 (Severe) = the worst their psoriasis has ever been. LS Means in Patient's Global Assessment of Disease Severity score were calculated using MMRM with baseline score as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects.
- Number of Participants Achieving Palmoplantar PASI of ≥50% (PPASI 50) Improvement [ Time Frame: Week 12 ]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 to 72. Participants achieving PPASI 50 were defined as having an improvement of at least 50% in the PPASI scores compared to baseline.
- Number of Participants Achieving Palmoplantar PASI of ≥75% (PPASI 75) Improvement [ Time Frame: Week 12 ]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 to 72. Participants achieving PPASI 75 were defined as having an improvement of at least 75% in the PPASI scores compared to baseline.
- Number of Participants Achieving Palmoplantar PASI of 100% (PPASI 100) Improvement [ Time Frame: Week 12 ]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 to 72. Participants achieving PPASI 100 were defined as having an improvement of 100% in the PPASI scores compared to baseline.
- Number of Participants With Treatment-Emergent Anti-Ixekizumab Antibodies [ Time Frame: Week 12 ]The percentage of participants with treatment-emergent positive anti-ixekizumab antibodies at any time post-baseline were summarized by treatment group. Percentage of participants with treatment-emergent positive anti-ixekizumab antibodies were calculated as: number of participants with an evaluable baseline sample and ≥1 evaluable post-baseline sample/number of participants in the analysis population * 100.
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Presents with chronic plaque psoriasis based on a confirmed diagnosis of chronic psoriasis 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 or remain abstinent during the study
- Women must agree to use reliable 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
- Prior use of etanercept
- Clinically significant flare of psoriasis during the 12 weeks prior to randomization
- Concurrent or recent use of any biologic agent
- Received non-biologic systemic psoriasis therapy or phototherapy (including psoralens and ultraviolet A [PUVA], ultraviolet B [UVB]) 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 17 (IL-17) antagonists, including ixekizumab
- Serious disorder or illness other than plaque psoriasis
- Serious infection within the last 3 months
- Breastfeeding or nursing (lactating) women
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01646177
Locations
Show 101 study locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
| 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 |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Eli Lilly and Company |
| ClinicalTrials.gov Identifier: | NCT01646177 |
| Other Study ID Numbers: |
13685 I1F-MC-RHBC ( Other Identifier: Eli Lilly and Company ) |
| First Posted: | July 20, 2012 Key Record Dates |
| Results First Posted: | October 21, 2016 |
| Last Update Posted: | July 28, 2020 |
| Last Verified: | November 1, 2019 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Clinical Study Report (CSR) |
| Time Frame: | Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting. |
| Access Criteria: | A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement. |
| URL: | https://vivli.org |
Additional relevant MeSH terms:
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Psoriasis Skin Diseases, Papulosquamous Skin Diseases Etanercept Ixekizumab Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics Sensory System Agents |
Peripheral Nervous System Agents Physiological Effects of Drugs Anti-Inflammatory Agents Antirheumatic Agents Gastrointestinal Agents Immunosuppressive Agents Immunologic Factors Dermatologic Agents |