Plaque Psoriasis
Conditions
Keywords
biologic, biologic therapy
Brief summary
The purpose of this study is to compare the efficacy and safety of ixekizumab to guselkumab in participants with moderate-to-severe plaque psoriasis.
Interventions
DRUGIxekizumab
Administered SC
DRUGGuselkumab
Administered SC
DRUGPlacebo
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have chronic plaque psoriasis based on a diagnosis for at least 6 months before baseline as determined by the investigator. * Are a candidate for phototherapy and/or systemic therapy. * Have both an Static Physician Global Assessment (sPGA) score of ≥3 and a Psoriasis Area and Severity Index (PASI) score ≥12 at screening and at baseline. * Have ≥10% body surface area (BSA) involvement at screening and baseline. * If a male, agree to use a reliable method of birth control during the study. * If female, agree to use highly effective method of contraception.
Exclusion criteria
* Predominant pattern of pustular, erythrodermic, and/or guttate forms of psoriasis. * Have a history of drug-induced psoriasis. * Had a clinically significant flare of psoriasis during the 12 weeks before baseline. * Use of tanning booths for at least 4 weeks before baseline. * Concurrent or recent use of any biologic agent within the following periods prior to baseline: etanercept \<28 days; infliximab, adalimumab, certolizumab pegol, or alefacept \<60 days; golimumab \<90 days; rituximab \<12 months; secukinumab \<5 months; or any other biologic agent (e.g., ustekinumab) \<5 half lives. * Have prior use of IL-23p19 antagonists (e.g., guselkumab, tildrakizumab, risankizumab), or have any condition or contraindication as addressed in the local labeling for guselkumab that would preclude the participant from participating in this protocol. * Have previously completed or withdrawn from this study, participated in any other study with ixekizumab or guselkumab, have participated in any study investigating IL-23p19 antagonists, or have received treatment with ixekizumab. * Have previously failed to respond to an IL-17 antagonist, per investigator assessment. * Have had a live vaccination within 12 weeks of baseline. * Have a known allergy or hypersensitivity to any biologic therapy. * Have had any major surgery within 8 weeks of baseline. * Have had a serious infection, have been hospitalized, or have received intravenous antibiotics for an infection within 12 weeks of baseline. * Are women who are pregnant, or who are lactating (breast-feeding).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving 100% Improvement From Baseline in Psoriasis Area and Severity Index (PASI 100) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving PASI 75 | Week 2 | 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 were defined as having an improvement of at least 75% in the PASI scores compared to baseline. |
| Percentage of Participants Achieving PASI 90 | Week 4 | 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. |
| Percentage of Participants Achieving PASI 100 | Week 4 | 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. |
| Percentage of Participants Achieving Static Physician Global Assessment (sPGA) (0) | 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. |
| Percentage of Participants Achieving PASI 50 | Week 1 | 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 50 were defined as having an improvement of at least 50% in the PASI scores compared to baseline. |
Countries
Canada, Puerto Rico, United States
Participant flow
Pre-assignment details
The study consists of a combined blinded treatment (trt) period with a 24-week duration followed by a post treatment follow-up (PTFU) period with a minimum of a 12-week duration. The Induction Dosing Period (12 Weeks) and Extension Period (12 Weeks) were combined for analysis and referred to as the blinded treatment periods.
Participants by arm
| Arm | Count |
|---|---|
| Ixekizumab A starting dose of 160 milligram (mg) of ixekizumab was given as 2 subcutaneous (SC) injections at Week 0. During the Induction Period, ixekizumab 80 mg was given every 2 weeks (Q2W) at Weeks 2, 4, 6, 8, 10, and 12. During the Extension Period, ixekizumab 80 mg was given as 1 SC injection (Q4W) every 4 weeks at Weeks 16 and 20. The Post Treatment Follow Up Period was for safety monitoring following the last treatment period. | 520 |
| Guselkumab During the Induction Period, guselkumab 100 mg was given as 1 SC injection at Weeks 0, 4 and 12. 1 placebo injection (to maintain the blind) was given at Weeks 0, 2, 6, 8, and 10. During the Extension Period, guselkumab 100 mg was given at Week 20. 1 placebo injection (to maintain the blind) was given at Week 16. The Post Treatment Follow Up Period was for safety monitoring following the last treatment period. | 507 |
| Total | 1,027 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Blinded Treatment Period (Weeks 0-24) | Adverse Event | 15 | 8 |
| Blinded Treatment Period (Weeks 0-24) | Alkaline Phosphatase (ALP) level reached | 0 | 1 |
| Blinded Treatment Period (Weeks 0-24) | Lack of Efficacy | 2 | 3 |
| Blinded Treatment Period (Weeks 0-24) | Lost to Follow-up | 14 | 13 |
| Blinded Treatment Period (Weeks 0-24) | Noncompliant to protocol procedures | 1 | 2 |
| Blinded Treatment Period (Weeks 0-24) | Physician Decision | 1 | 0 |
| Blinded Treatment Period (Weeks 0-24) | Pregnancy | 1 | 2 |
| Blinded Treatment Period (Weeks 0-24) | Protocol Violation | 3 | 8 |
| Blinded Treatment Period (Weeks 0-24) | Screen Failure | 1 | 1 |
| Blinded Treatment Period (Weeks 0-24) | Sponsor Decision | 0 | 1 |
| Blinded Treatment Period (Weeks 0-24) | Withdrawal by Subject | 17 | 9 |
| Post-Treatment Follow Up (Weeks 25-36) | Did not wish to return to study | 3 | 2 |
| Post-Treatment Follow Up (Weeks 25-36) | Discontinued Trt and Completed Follow Up | 14 | 8 |
| Post-Treatment Follow Up (Weeks 25-36) | Lack of Efficacy | 8 | 19 |
| Post-Treatment Follow Up (Weeks 25-36) | Not Compliant to Protocol Procedures | 8 | 11 |
| Post-Treatment Follow Up (Weeks 25-36) | Physician Decision | 4 | 3 |
| Post-Treatment Follow Up (Weeks 25-36) | Repeat Infections | 0 | 1 |
| Post-Treatment Follow Up (Weeks 25-36) | Sponsor Decision | 0 | 1 |
| Post-Treatment Follow Up (Weeks 25-36) | Withdrawal by Subject | 22 | 12 |
Baseline characteristics
| Characteristic | Ixekizumab | Total | Guselkumab |
|---|---|---|---|
| Age, Continuous | 49.0 years STANDARD_DEVIATION 13.9 | 49.0 years STANDARD_DEVIATION 14.39 | 49.0 years STANDARD_DEVIATION 14.88 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 127 Participants | 247 Participants | 120 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 383 Participants | 762 Participants | 379 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 10 Participants | 18 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 7 Participants | 13 Participants | 6 Participants |
| Race (NIH/OMB) Asian | 31 Participants | 66 Participants | 35 Participants |
| Race (NIH/OMB) Black or African American | 38 Participants | 67 Participants | 29 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 439 Participants | 870 Participants | 431 Participants |
| Region of Enrollment Canada | 103 Participants | 209 Participants | 106 Participants |
| Region of Enrollment United States | 417 Participants | 818 Participants | 401 Participants |
| Sex: Female, Male Female | 182 Participants | 375 Participants | 193 Participants |
| Sex: Female, Male Male | 338 Participants | 652 Participants | 314 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 519 | 0 / 506 | 0 / 465 | 0 / 456 |
| other Total, other adverse events | 113 / 519 | 73 / 506 | 11 / 465 | 9 / 456 |
| serious Total, serious adverse events | 18 / 519 | 16 / 506 | 4 / 465 | 4 / 456 |
Outcome results
Primary
Percentage of Participants Achieving 100% Improvement From Baseline in Psoriasis Area and Severity Index (PASI 100)
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.
Time frame: Week 12
Population: All randomized participants. Participants who did not meet clinical response criteria or have missing data at Week 12 were considered as non-responders for the Non-Responder Imputation (NRI) analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ixekizumab | Percentage of Participants Achieving 100% Improvement From Baseline in Psoriasis Area and Severity Index (PASI 100) | 41.3 percentage of participants |
| Guselkumab | Percentage of Participants Achieving 100% Improvement From Baseline in Psoriasis Area and Severity Index (PASI 100) | 24.9 percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving PASI 100
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.
Time frame: Week 24
Population: All randomized participants. Participants who did not meet clinical response criteria or have missing data at Week 12 were considered as non-responders for the Non-Responder Imputation (NRI) analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ixekizumab | Percentage of Participants Achieving PASI 100 | 50.0 percentage of participants |
| Guselkumab | Percentage of Participants Achieving PASI 100 | 52.3 percentage of participants |
p-value: 0.414Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving PASI 100
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.
Time frame: Week 4
Population: All randomized participants. Participants who did not meet clinical response criteria or have missing data at Week 12 were considered as non-responders for the Non-Responder Imputation (NRI) analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ixekizumab | Percentage of Participants Achieving PASI 100 | 6.7 percentage of participants |
| Guselkumab | Percentage of Participants Achieving PASI 100 | 1.4 percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving PASI 100
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.
Time frame: Week 8
Population: All randomized participants. Participants who did not meet clinical response criteria or have missing data at Week 12 were considered as non-responders for the Non-Responder Imputation (NRI) analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ixekizumab | Percentage of Participants Achieving PASI 100 | 29.6 percentage of participants |
| Guselkumab | Percentage of Participants Achieving PASI 100 | 13.6 percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving PASI 50
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 50 were defined as having an improvement of at least 50% in the PASI scores compared to baseline.
Time frame: Week 1
Population: All randomized participants. Participants who did not meet clinical response criteria or have missing data at Week 12 were considered as non-responders for the Non-Responder Imputation (NRI) analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ixekizumab | Percentage of Participants Achieving PASI 50 | 27.5 percentage of participants |
| Guselkumab | Percentage of Participants Achieving PASI 50 | 9.3 percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving PASI 75
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 were defined as having an improvement of at least 75% in the PASI scores compared to baseline.
Time frame: Week 2
Population: All randomized participants. Participants who did not meet clinical response criteria or have missing data at Week 12 were considered as non-responders for the Non-Responder Imputation (NRI) analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ixekizumab | Percentage of Participants Achieving PASI 75 | 22.9 percentage of participants |
| Guselkumab | Percentage of Participants Achieving PASI 75 | 5.1 percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving PASI 90
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.
Time frame: Week 8
Population: All randomized participants. Participants who did not meet clinical response criteria or have missing data at Week 12 were considered as non-responders for the Non-Responder Imputation (NRI) analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ixekizumab | Percentage of Participants Achieving PASI 90 | 58.5 percentage of participants |
| Guselkumab | Percentage of Participants Achieving PASI 90 | 35.9 percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving PASI 90
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.
Time frame: Week 4
Population: All randomized participants. Participants who did not meet clinical response criteria or have missing data at Week 12 were considered as non-responders for the Non-Responder Imputation (NRI) analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ixekizumab | Percentage of Participants Achieving PASI 90 | 21.0 percentage of participants |
| Guselkumab | Percentage of Participants Achieving PASI 90 | 7.9 percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Static Physician Global Assessment (sPGA) (0)
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.
Time frame: Week 12
Population: All randomized participants. Participants who did not meet clinical response criteria or have missing data at Week 12 were considered as non-responders for the Non-Responder Imputation (NRI) analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ixekizumab | Percentage of Participants Achieving Static Physician Global Assessment (sPGA) (0) | 41.9 percentage of participants |
| Guselkumab | Percentage of Participants Achieving Static Physician Global Assessment (sPGA) (0) | 25.2 percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel