Plaque Psoriasis
Conditions
Keywords
Plaque psoriasis, secukinumab, ustekinumab, ain457, ain457a
Brief summary
Demonstrate superiority of secukinumab over ustekinumab in treatment of moderate to severe plaque psoriasis.
Interventions
DRUGSecukinumab
300mg, s.c. at randomization, Weeks 1, 2 and 3 and thereafter 4-weekly till Week 48
DRUGUstekinumab
Per approved label, 45 mg or 90 mg s.c. based on subject weight (at randomization visit) to be administered at randomization, Week 4, 16, 28 and 40. At other timepoints subjects will receive placebo injections.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must give a written, signed and dated informed consent * Chronic plaque-type psoriasis present for at least 6 months before randomization * Moderate to severe plaque psoriasis as defined at randomization by: * PASI score of ≥12 and * Body Surface Area (BSA) affected by plaque-type psoriasis ≥10% and * IGA mod 2011 ≥3 (based on a scale of 0-4) * Candidate for systemic therapy, defined as having psoriasis inadequately controlled by: * Topical treatment (including topical corticosteroids) and/or * Phototherapy and/or * Previous systemic therapy
Exclusion criteria
* Forms of psoriasis other than plaque psoriasis * Drug-induced psoriasis * Ongoing use of prohibited treatments * Previous exposure to secukinumab or any other biologic drug directly targeting IL-17A or IL-17RA, or ustekinumab, or any therapies targeting IL-12 or IL-23 * Use of any other investigational drugs within 5 half-lives of the investigational treatment before study drug initiation * Pregnant or nursing (lactating) women Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants Who Achieved Psoriasis Area and Severity Index (PASI) 90 Response at Week 12 | Week 12 | Number of participants who achieved ≥ 90% reduction in PASI compared to baseline. Logistic regression analysis of PASI 90 response at Week 12 PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, upper limbs, trunk, lower limbs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area\* area score weight of body region(head: 0.1, upper limbs: 0.2, trunk: 0.3, lower limbs: 0.4). |
| Participants With IGA Mod 2011 0 or 1 at Week 12 | Week 12 | Investigator's Global Assessment uses a scale (IGA mod 2011) that rates disease from a score of 0 (clear skin) to 4 (severe disease) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants Who Achieved Psoriasis Area and Severity Index (PASI) 100 Response at Week 16 | Week 16 | Number of participants who achieved 100% reduction in PASI at Week 16 compared to baseline. |
| Participants With IGA Mod 2011 0 or 1 at 16 Weeks | Week 16 | Investigator's Global Assessment uses a scale (IGA mod 2011) that rates disease from a score of 0 (clear skin) to 4 (severe disease) |
| Participants Who Achieved Psoriasis Area and Severity Index (PASI) 100 Response at Week 12 | Week 12 | Number of participants who achieved 100% reduction in PASI at Week 12 compared to baseline. |
| Participants Who Achieved Psoriasis Area and Severity Index (PASI) 75 Response at Week 12 | Week 12 | Number of participants who achieved ≥ 75% reduction in PASI at Week 12 compared to baseline. |
| Participants Who Achieved Psoriasis Area and Severity Index (PASI) 90 Response at Week 16 | Week 16 | Number of participants who achieved ≥ 90% reduction in PASI at Week 16 compared to baseline. |
| Participants Who Achieved Psoriasis Area and Severity Index (PASI) 90 Response at Week 52 | Week 52 | Number of participants who achieved ≥ 90% reduction in PASI at Week 52 compared to baseline. |
| Participants Who Achieved Psoriasis Area and Severity Index (PASI) 75 Response at Week 16 | Week 16 | Number of participants who achieved ≥ 75% reduction in PASI at Week 16 compared to baseline. |
| Participants Who Achieved Psoriasis Area and Severity Index (PASI) 75 Response at Week 4 | Week 4 | Number of participants who achieved ≥ 75% reduction in PASI at Week 4 compared to baseline. |
Countries
Canada, Czechia, Guatemala, Hungary, Iceland, Malaysia, Poland, Slovakia, South Korea, United States, Vietnam
Participant flow
Recruitment details
Overall, 1353 patients were screened of which 1102 patients completed the Screening phase; 251 patients were screen failures
Pre-assignment details
The randomized set was defined as all patients who were randomized at the baseline visit. Unless otherwise specified, mis-randomized patients were excluded from the randomized set. Mis-randomized patients were those who were screen failures, but had been randomized by the Investigator before eligibility was assessed, but had not been treated
Participants by arm
| Arm | Count |
|---|---|
| Secukinumab 300mg (2 x 150 mg) Secukinumab 300mg s.c. injection (2 150mg pre-fiilled syringes) | 550 |
| Ustekinumab 2 x 45mg or 90mg Ustekinumab s.c. 45 mg or 90 mg (depending on body weight) using 45mg pre-filled syringes (1 or 2 syringes) | 552 |
| Total | 1,102 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 17 | 9 |
| Overall Study | Death | 2 | 0 |
| Overall Study | Lack of Efficacy | 4 | 9 |
| Overall Study | Lost to Follow-up | 13 | 12 |
| Overall Study | New therapy for study indication | 0 | 1 |
| Overall Study | Noncompliance with treatment | 0 | 2 |
| Overall Study | Physician Decision | 1 | 7 |
| Overall Study | Pregnancy | 1 | 2 |
| Overall Study | Protocol Violation | 3 | 3 |
| Overall Study | Withdrawal by Subject | 20 | 19 |
Baseline characteristics
| Characteristic | Ustekinumab 2 x 45mg or 90mg | Secukinumab 300mg (2 x 150 mg) | Total |
|---|---|---|---|
| Age, Continuous | 45.3 years STANDARD_DEVIATION 14.16 | 45.4 years STANDARD_DEVIATION 14.09 | 45.4 years STANDARD_DEVIATION 14.12 |
| Age, Customized <65 years | 494 Participants | 488 Participants | 982 Participants |
| Age, Customized >=65 years and <75 years | 48 Participants | 60 Participants | 108 Participants |
| Age, Customized >=75 years | 10 Participants | 2 Participants | 12 Participants |
| Race/Ethnicity, Customized Asian | 57 Participants | 60 Participants | 117 Participants |
| Race/Ethnicity, Customized Black | 24 Participants | 21 Participants | 45 Participants |
| Race/Ethnicity, Customized Caucasian | 410 Participants | 416 Participants | 826 Participants |
| Race/Ethnicity, Customized Native American | 41 Participants | 34 Participants | 75 Participants |
| Race/Ethnicity, Customized Other | 13 Participants | 14 Participants | 27 Participants |
| Race/Ethnicity, Customized Pacific Islander | 5 Participants | 1 Participants | 6 Participants |
| Race/Ethnicity, Customized Unknown | 2 Participants | 4 Participants | 6 Participants |
| Sex: Female, Male Female | 176 Participants | 194 Participants | 370 Participants |
| Sex: Female, Male Male | 376 Participants | 356 Participants | 732 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 550 | 0 / 552 | 2 / 1,102 |
| other Total, other adverse events | 216 / 550 | 229 / 552 | 445 / 1,102 |
| serious Total, serious adverse events | 29 / 550 | 21 / 552 | 50 / 1,102 |
Outcome results
Primary
Participants Who Achieved Psoriasis Area and Severity Index (PASI) 90 Response at Week 12
Number of participants who achieved ≥ 90% reduction in PASI compared to baseline. Logistic regression analysis of PASI 90 response at Week 12 PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, upper limbs, trunk, lower limbs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area\* area score weight of body region(head: 0.1, upper limbs: 0.2, trunk: 0.3, lower limbs: 0.4).
Time frame: Week 12
Population: The Full analysis set (FAS) is all patients from the randomized set assigned to study treatment. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned at randomization. If the actual randomization stratum was different to the assigned stratum in IRT, the actual stratum was used in the analyses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 300mg (2 x 150 mg) | Participants Who Achieved Psoriasis Area and Severity Index (PASI) 90 Response at Week 12 | 366 Participants |
| Ustekinumab 2 x 45mg or 90mg | Participants Who Achieved Psoriasis Area and Severity Index (PASI) 90 Response at Week 12 | 265 Participants |
p-value: <0.000195% CI: [1.72, 2.84]Regression, Logistic
Primary
Participants With IGA Mod 2011 0 or 1 at Week 12
Investigator's Global Assessment uses a scale (IGA mod 2011) that rates disease from a score of 0 (clear skin) to 4 (severe disease)
Time frame: Week 12
Population: The full analysis set (FAS) population was used for this analysis. The FAS included all participants to whom treatment was assigned. Only participants from the FAS, who had values at a given week, were included in the analysis for that week.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 300mg (2 x 150 mg) | Participants With IGA Mod 2011 0 or 1 at Week 12 | 397 Participants |
| Ustekinumab 2 x 45mg or 90mg | Participants With IGA Mod 2011 0 or 1 at Week 12 | 306 Participants |
p-value: <0.000195% CI: [1.63, 2.72]Regression, Logistic
Secondary
Participants Who Achieved Psoriasis Area and Severity Index (PASI) 100 Response at Week 12
Number of participants who achieved 100% reduction in PASI at Week 12 compared to baseline.
Time frame: Week 12
Population: FAS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 300mg (2 x 150 mg) | Participants Who Achieved Psoriasis Area and Severity Index (PASI) 100 Response at Week 12 | 210 Participants |
| Ustekinumab 2 x 45mg or 90mg | Participants Who Achieved Psoriasis Area and Severity Index (PASI) 100 Response at Week 12 | 111 Participants |
p-value: <0.000195% CI: [1.89, 3.31]Regression, Logistic
Secondary
Participants Who Achieved Psoriasis Area and Severity Index (PASI) 100 Response at Week 16
Number of participants who achieved 100% reduction in PASI at Week 16 compared to baseline.
Time frame: Week 16
Population: FAS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 300mg (2 x 150 mg) | Participants Who Achieved Psoriasis Area and Severity Index (PASI) 100 Response at Week 16 | 250 Participants |
| Ustekinumab 2 x 45mg or 90mg | Participants Who Achieved Psoriasis Area and Severity Index (PASI) 100 Response at Week 16 | 147 Participants |
p-value: <0.000195% CI: [1.8, 3.01]Regression, Logistic
Secondary
Participants Who Achieved Psoriasis Area and Severity Index (PASI) 75 Response at Week 12
Number of participants who achieved ≥ 75% reduction in PASI at Week 12 compared to baseline.
Time frame: Week 12
Population: FAS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 300mg (2 x 150 mg) | Participants Who Achieved Psoriasis Area and Severity Index (PASI) 75 Response at Week 12 | 484 Participants |
| Ustekinumab 2 x 45mg or 90mg | Participants Who Achieved Psoriasis Area and Severity Index (PASI) 75 Response at Week 12 | 409 Participants |
p-value: <0.000195% CI: [1.89, 3.62]Regression, Logistic
Secondary
Participants Who Achieved Psoriasis Area and Severity Index (PASI) 75 Response at Week 16
Number of participants who achieved ≥ 75% reduction in PASI at Week 16 compared to baseline.
Time frame: Week 16
Population: FAS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 300mg (2 x 150 mg) | Participants Who Achieved Psoriasis Area and Severity Index (PASI) 75 Response at Week 16 | 506 Participants |
| Ustekinumab 2 x 45mg or 90mg | Participants Who Achieved Psoriasis Area and Severity Index (PASI) 75 Response at Week 16 | 441 Participants |
p-value: <0.000195% CI: [1.96, 4.17]Regression, Logistic
Secondary
Participants Who Achieved Psoriasis Area and Severity Index (PASI) 75 Response at Week 4
Number of participants who achieved ≥ 75% reduction in PASI at Week 4 compared to baseline.
Time frame: Week 4
Population: FAS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 300mg (2 x 150 mg) | Participants Who Achieved Psoriasis Area and Severity Index (PASI) 75 Response at Week 4 | 221 Participants |
| Ustekinumab 2 x 45mg or 90mg | Participants Who Achieved Psoriasis Area and Severity Index (PASI) 75 Response at Week 4 | 90 Participants |
p-value: <0.000195% CI: [2.65, 4.71]Regression, Logistic
Secondary
Participants Who Achieved Psoriasis Area and Severity Index (PASI) 90 Response at Week 16
Number of participants who achieved ≥ 90% reduction in PASI at Week 16 compared to baseline.
Time frame: Week 16
Population: FAS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 300mg (2 x 150 mg) | Participants Who Achieved Psoriasis Area and Severity Index (PASI) 90 Response at Week 16 | 423 Participants |
| Ustekinumab 2 x 45mg or 90mg | Participants Who Achieved Psoriasis Area and Severity Index (PASI) 90 Response at Week 16 | 299 Participants |
p-value: <0.000195% CI: [2.19, 3.71]Regression, Logistic
Secondary
Participants Who Achieved Psoriasis Area and Severity Index (PASI) 90 Response at Week 52
Number of participants who achieved ≥ 90% reduction in PASI at Week 52 compared to baseline.
Time frame: Week 52
Population: FAS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 300mg (2 x 150 mg) | Participants Who Achieved Psoriasis Area and Severity Index (PASI) 90 Response at Week 52 | 402 Participants |
| Ustekinumab 2 x 45mg or 90mg | Participants Who Achieved Psoriasis Area and Severity Index (PASI) 90 Response at Week 52 | 330 Participants |
p-value: <0.000195% CI: [1.41, 2.41]Regression, Logistic
Secondary
Participants With IGA Mod 2011 0 or 1 at 16 Weeks
Investigator's Global Assessment uses a scale (IGA mod 2011) that rates disease from a score of 0 (clear skin) to 4 (severe disease)
Time frame: Week 16
Population: The full analysis set (FAS) population was used for this analysis. The FAS included all participants to whom treatment was assigned. Only participants from the FAS, who had values at a given week, were included in the analysis for that week.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 300mg (2 x 150 mg) | Participants With IGA Mod 2011 0 or 1 at 16 Weeks | 432 Participants |
| Ustekinumab 2 x 45mg or 90mg | Participants With IGA Mod 2011 0 or 1 at 16 Weeks | 326 Participants |
p-value: <0.000195% CI: [1.96, 3.37]Regression, Logistic