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 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.
Detailed description
This study 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
DRUGustekinumab
45 mg or 90 mg ustekinumab administered SC per the labeled dosing regimen.
DRUGplacebo
placebo administered SC
210 mg brodalumab administered SC
140 mg brodalumab 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 Psoriasis Area Severity Index (PASI) 75 at Week 12 | 12 weeks | The Psoriasis Area and Severity Index Score is used as a scale to show change from Baseline of study to a certain point. PASI Score ranges from (0) no disease to (72) maximal disease. The proportion of subjects achieving 75% improvement in Psoriasis Area and Severity Index, PASI75, was assessed. |
| Percentage of Participants With Static Physician Global Assessment (sPGA) Success Score (Score of 0 or 1) at Week 12 - Comparison to Placebo | 12 weeks | Static Physician Global Assessment (sPGA) measures the physician's impression of the disease. Possible scores are (0 \[clear\] to 5 \[severe\]). Success was defined by a score of 0 or 1 (clear to almost clear). |
Countries
Australia, Belgium, Canada, France, Greece, Hungary, Italy, Latvia, Poland, Russia, 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 | 624 |
| 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 | 629 |
| 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. | 313 |
| Placebo Administered by 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 | 315 |
| Total | 1,881 |
Baseline characteristics
| Characteristic | 210 mg Brodalumab | 140 mg Brodalumab | Ustekinumab | Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 46 Participants | 40 Participants | 21 Participants | 15 Participants | 122 Participants |
| Age, Categorical Between 18 and 65 years | 578 Participants | 589 Participants | 292 Participants | 300 Participants | 1759 Participants |
| Age, Continuous | 45.2 years STANDARD_DEVIATION 13.3 | 44.6 years STANDARD_DEVIATION 13 | 44.8 years STANDARD_DEVIATION 13.1 | 44.2 years STANDARD_DEVIATION 12.5 | 44.8 years STANDARD_DEVIATION 13 |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 3 Participants | 1 Participants | 0 Participants | 7 Participants |
| Race (NIH/OMB) Asian | 20 Participants | 27 Participants | 12 Participants | 9 Participants | 68 Participants |
| Race (NIH/OMB) Black or African American | 17 Participants | 22 Participants | 13 Participants | 6 Participants | 58 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants | 3 Participants | 1 Participants | 1 Participants | 8 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 14 Participants | 4 Participants | 6 Participants | 5 Participants | 29 Participants |
| Race (NIH/OMB) White | 565 Participants | 569 Participants | 280 Participants | 294 Participants | 1708 Participants |
| Region of Enrollment Australia | 17 participants | 16 participants | 9 participants | 8 participants | 50 participants |
| Region of Enrollment Belgium | 8 participants | 8 participants | 3 participants | 6 participants | 24 participants |
| Region of Enrollment Canada | 72 participants | 75 participants | 38 participants | 34 participants | 219 participants |
| Region of Enrollment France | 28 participants | 29 participants | 14 participants | 16 participants | 88 participants |
| Region of Enrollment Greece | 21 participants | 23 participants | 11 participants | 10 participants | 65 participants |
| Region of Enrollment Hungary | 17 participants | 16 participants | 10 participants | 7 participants | 50 participants |
| Region of Enrollment Italy | 2 participants | 3 participants | 1 participants | 2 participants | 8 participants |
| Region of Enrollment Latvia | 33 participants | 32 participants | 15 participants | 16 participants | 96 participants |
| Region of Enrollment Poland | 127 participants | 128 participants | 63 participants | 63 participants | 381 participants |
| Region of Enrollment Russia | 23 participants | 21 participants | 9 participants | 12 participants | 65 participants |
| Region of Enrollment United States | 276 participants | 278 participants | 140 participants | 141 participants | 835 participants |
| Sex: Female, Male Female | 193 Participants | 192 Participants | 101 Participants | 107 Participants | 593 Participants |
| Sex: Female, Male Male | 431 Participants | 437 Participants | 212 Participants | 208 Participants | 1288 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 | 353 / 624 | 329 / 629 | 152 / 315 | 168 / 313 |
| serious Total, serious adverse events | 9 / 624 | 10 / 629 | 3 / 315 | 2 / 313 |
Outcome results
Primary
Percentage of Participants With Psoriasis Area Severity Index (PASI) 75 at Week 12
The Psoriasis Area and Severity Index Score is used as a scale to show change from Baseline of study to a certain point. PASI Score ranges from (0) no disease to (72) maximal disease. The proportion of subjects achieving 75% improvement in Psoriasis Area and Severity Index, PASI75, was assessed.
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 | 531 Participants |
| 140 mg Brodalumab | Percentage of Participants With Psoriasis Area Severity Index (PASI) 75 at Week 12 | 435 Participants |
| Placebo | Percentage of Participants With Psoriasis Area Severity Index (PASI) 75 at Week 12 | 19 Participants |
| Ustekinumab | Percentage of Participants With Psoriasis Area Severity Index (PASI) 75 at Week 12 | 217 Participants |
Primary
Percentage of Participants With Static Physician Global Assessment (sPGA) Success Score (Score of 0 or 1) at Week 12 - Comparison to Placebo
Static Physician Global Assessment (sPGA) measures the physician's impression of the disease. Possible scores are (0 \[clear\] to 5 \[severe\]). Success was defined by a score of 0 or 1 (clear to almost clear).
Time frame: 12 weeks
Population: sPGA was only assessed as a comparison of Brodalumab (210mg and 140mg) to Placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 210 mg Brodalumab | Percentage of Participants With Static Physician Global Assessment (sPGA) Success Score (Score of 0 or 1) at Week 12 - Comparison to Placebo | 497 Participants |
| 140 mg Brodalumab | Percentage of Participants With Static Physician Global Assessment (sPGA) Success Score (Score of 0 or 1) at Week 12 - Comparison to Placebo | 377 Participants |
| Placebo | Percentage of Participants With Static Physician Global Assessment (sPGA) Success Score (Score of 0 or 1) at Week 12 - Comparison to Placebo | 13 Participants |