Moderate to Severe Plaque Psoriasis
Conditions
Keywords
psoriasis, brodalumab, AMG 827
Brief summary
The purpose of this study is to assess the safety and efficacy of brodalumab at two different doses
Detailed description
.The purpose of this study is to assess the safety and efficacy of brodalumab at two different doses compared with placebo in participants with moderate to severe plaque psoriasis. A second purpose of this study is to assess the safety and efficacy brodalumab at two different doses compared with ustekinumab in participants with moderate to severe plaque psoriasis. A third purpose of this study is to assess the safety and efficacy of 4 maintenance regimens of brodalumab.
Interventions
210 mg brodalumab administered SC
140 mg brodalumab administered SC
DRUGustekinumab
45 mg or 90 mg ustekinumab administered SC per the labeled dosing regimen.
DRUGplacebo
Placebo administered SC
Sponsors
Bausch Health Americas, Inc.
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 75 Years
Healthy volunteers
No
Inclusion criteria
* Subject has had stable moderate to severe plaque psoriasis for at least 6 months * Subject has involved body surface area (BSA) ≥ 10%, PASI ≥ 12, and sPGA ≥ 3 at screening and at baseline
Exclusion criteria
* Subject diagnosed with erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, medication-induced psoriasis, or other skin conditions at (eg, eczema) that would interfere with study evaluations * Subject has known history of Crohn's disease * Subject has any other significant concurrent medical condition or laboratory abnormalities, as defined in the study protocol * Subject has not stopped using certain psoriasis therapies as defined in the study protocol * Subject has previously used ustekinumab or any anti-IL-17 biologic therapy * Subject is pregnant or breastfeeding, or planning to become pregnant while enrolled in the study * Female subject is unwilling to use highly effective methods of birth control unless 2 years post-menopausal or surgically sterile
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Static Physician Global Assessment (sPGA) Score Success (Score of 0 or 1) at Week 12 | 12 weeks | Measures the physician's impression of the disease at a single point, and a dynamic form in which the physician assesses the global improvement from baseline. Success is defined by a score of 0 or 1 (clear to almost clear). |
| Percentage of Participants With Psoriasis Area Severity Index (PASI) 75 at Week 12 | 12 weeks | to evaluate the efficacy of Brodalumab (210mg every 2 weeks, and 140mg every 2 weeks) in subjects with moderate to severe plaque psoriasis, as measured by the proportion of subjects achieving 75% improvement in Psoriasis Area and Severity Index, PASI75 at week 12. |
| Percentage of Participants With Psoriasis Area Severity Index (PASI) 100 at Week 12 | 12 Weeks | to evaluate the efficacy of Brodalumab (210mg Q2W) in clearing psoriasis as measured by the proportion of subjects achieving PASI 100 at week 12. |
Countries
Australia, Austria, Canada, Czechia, France, Hungary, Netherlands, Poland, Portugal, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 210 mg Brodalumab Administered by subcutaneous (SC) injection until week 12. At week 12, participants are rerandomized to schedule 1, 2, 3, or 4.
210 mg brodalumab: 210 mg brodalumab administered SC | 612 |
| 140 mg Brodalumab Administered by subcutaneous (SC) injection until week 12. At week 12, participants are rerandomized to schedule 1, 2, 3, or 4.
140 mg brodalumab: 140 mg brodalumab administered SC | 610 |
| Ustekinumab Administered by subcutaneous (SC) injection per the labeled dosing regimen.
ustekinumab: 45 mg or 90 mg ustekinumab administered SC per the labeled dosing regimen. | 300 |
| Placebo Administered by subcutaneous (SC) injection until week 12. At week 12 participants are assigned to 210 mg brodalumab.
210 mg brodalumab: 210 mg brodalumab administered SC
placebo: Placebo administered SC | 309 |
| Total | 1,831 |
Baseline characteristics
| Characteristic | 210 mg Brodalumab | Total | Placebo | Ustekinumab | 140 mg Brodalumab |
|---|---|---|---|---|---|
| Age, Continuous | 44.5 years STANDARD_DEVIATION 12.7 | 44.6 years STANDARD_DEVIATION 12.8 | 43.7 years STANDARD_DEVIATION 12.9 | 45.4 years STANDARD_DEVIATION 13 | 44.8 years STANDARD_DEVIATION 12.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 8 Participants | 2 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 19 Participants | 68 Participants | 12 Participants | 12 Participants | 25 Participants |
| Race (NIH/OMB) Black or African American | 19 Participants | 53 Participants | 14 Participants | 7 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 10 Participants | 1 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 5 Participants | 9 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 10 Participants | 31 Participants | 7 Participants | 6 Participants | 8 Participants |
| Race (NIH/OMB) White | 551 Participants | 1652 Participants | 273 Participants | 271 Participants | 557 Participants |
| Region of Enrollment Australia | 40 participants | 118 participants | 19 participants | 20 participants | 39 participants |
| Region of Enrollment Austria | 6 participants | 20 participants | 4 participants | 2 participants | 8 participants |
| Region of Enrollment Canada | 64 participants | 195 participants | 33 participants | 32 participants | 66 participants |
| Region of Enrollment Czechia | 18 participants | 53 participants | 8 participants | 7 participants | 20 participants |
| Region of Enrollment France | 14 participants | 44 participants | 8 participants | 9 participants | 13 participants |
| Region of Enrollment Hungary | 18 participants | 50 participants | 10 participants | 8 participants | 15 participants |
| Region of Enrollment Netherlands | 5 participants | 17 participants | 3 participants | 3 participants | 6 participants |
| Region of Enrollment Poland | 130 participants | 391 participants | 64 participants | 65 participants | 132 participants |
| Region of Enrollment Portugal | 12 participants | 32 participants | 6 participants | 4 participants | 10 participants |
| Region of Enrollment Spain | 19 participants | 59 participants | 10 participants | 10 participants | 20 participants |
| Region of Enrollment United States | 286 participants | 851 participants | 144 participants | 140 participants | 281 participants |
| Sex: Female, Male Female | 191 Participants | 573 Participants | 90 Participants | 95 Participants | 197 Participants |
| Sex: Female, Male Male | 421 Participants | 1258 Participants | 219 Participants | 205 Participants | 413 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 | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 354 / 612 | 365 / 610 | 177 / 300 | 165 / 309 |
| serious Total, serious adverse events | 6 / 612 | 13 / 610 | 4 / 300 | 8 / 309 |
Outcome results
Primary
Percentage of Participants With Psoriasis Area Severity Index (PASI) 100 at Week 12
to evaluate the efficacy of Brodalumab (210mg Q2W) in clearing psoriasis as measured by the proportion of subjects achieving PASI 100 at week 12.
Time frame: 12 Weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 210 mg Brodalumab | Percentage of Participants With Psoriasis Area Severity Index (PASI) 100 at Week 12 | 272 Participants |
| 140 mg Brodalumab | Percentage of Participants With Psoriasis Area Severity Index (PASI) 100 at Week 12 | 157 Participants |
| Placebo | Percentage of Participants With Psoriasis Area Severity Index (PASI) 100 at Week 12 | 2 Participants |
| Ustekinumab | Percentage of Participants With Psoriasis Area Severity Index (PASI) 100 at Week 12 | 65 Participants |
Primary
Percentage of Participants With Psoriasis Area Severity Index (PASI) 75 at Week 12
to evaluate the efficacy of Brodalumab (210mg every 2 weeks, and 140mg every 2 weeks) in subjects with moderate to severe plaque psoriasis, as measured by the proportion of subjects achieving 75% improvement in Psoriasis Area and Severity Index, PASI75 at week 12.
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 210 mg Brodalumab | Percentage of Participants With Psoriasis Area Severity Index (PASI) 75 at Week 12 | 528 Participants |
| 140 mg Brodalumab | Percentage of Participants With Psoriasis Area Severity Index (PASI) 75 at Week 12 | 406 Participants |
| Placebo | Percentage of Participants With Psoriasis Area Severity Index (PASI) 75 at Week 12 | 25 Participants |
| Ustekinumab | Percentage of Participants With Psoriasis Area Severity Index (PASI) 75 at Week 12 | 210 Participants |
Primary
Percentage of Participants With Static Physician Global Assessment (sPGA) Score Success (Score of 0 or 1) at Week 12
Measures the physician's impression of the disease at a single point, and a dynamic form in which the physician assesses the global improvement from baseline. Success is defined by a score of 0 or 1 (clear to almost clear).
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 210 mg Brodalumab | Percentage of Participants With Static Physician Global Assessment (sPGA) Score Success (Score of 0 or 1) at Week 12 | 481 Participants |
| 140 mg Brodalumab | Percentage of Participants With Static Physician Global Assessment (sPGA) Score Success (Score of 0 or 1) at Week 12 | 354 Participants |
| Placebo | Percentage of Participants With Static Physician Global Assessment (sPGA) Score Success (Score of 0 or 1) at Week 12 | 12 Participants |
| Ustekinumab | Percentage of Participants With Static Physician Global Assessment (sPGA) Score Success (Score of 0 or 1) at Week 12 | 183 Participants |