Psoriasis
Conditions
Keywords
Psoriasis, Plaque Psoriasis, Risankizumab, ABBV-066, Skyrizi, Apremilast
Brief summary
Psoriasis (PsO) is a chronic disease characterized by marked inflammation of the skin that results in thick, red, scaly plaques. This study will assess how safe and effective risankizumab is compared to apremilast in adult participants with moderate plaque psoriasis. Adverse events and change in disease symptoms will be monitored. Risankizumab (Skyrizi) and apremilast are approved drugs for the treatment of moderate to severe PsO. Approximately 330 participants with moderate plaque psoriasis (PsO) will be enrolled across approximately 55 sites globally. The study has 2 periods : Period A from Baseline to Week 16, and Period B, from Week 16 to Week 52. In Period A, participants will be randomly placed into 2 groups to receive either subcutaneous risankizumab or oral apremilast for 16 weeks. In Period B, participants who received apremilast in Period A will again be randomly assigned to 1 of the 2 groups to receive either risankizumab or apremilast for 36 weeks. At weeks 28 and 40, participants considered non-responders to apremilast based on their psoriasis score will be offered to receive risankizumab. There may be a higher burden for participants in this study compared to usual standard of care. Participants will attend regular visits per routine clinical practice. The effect of the treatment will be checked by medical assessments, checking for side effects, and questionnaires.
Interventions
DRUGRisankizumab
Subcutaneous injection
DRUGApremilast
Oral Tablets
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\- Candidates for systemic therapy with moderate chronic plaque psoriasis (PsO) (with or without psoriatic arthritis) at Screening and Baseline for at least 6 months prior to Baseline defined as: * Body Surface Area (BSA) \>= 10% and \<= 15%; and * Psoriasis Area and Severity Index (PASI) \>= 12; and * Static Physician Global Assessment (sPGA) = 3 (moderate) based on a 5-point scale (0 to 4).
Exclusion criteria
* Participant has any form of PsO other than chronic plaque PsO (e.g., pustular PsO, palmoplantar pustulosis, acrodermatitis of Hallopeau, erythrodermic, or guttate PsO). * History of current drug-induced PsO or a drug-induced exacerbation of pre-existing psoriasis. * History of active ongoing inflammatory skin diseases other than PsO and psoriatic arthritis that could interfere with the assessment of PsO (e.g., hyperkeratotic eczema). * Prior exposure to risankizumab or apremilast.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Psoriasis Area Severity Index (PASI) 90 (Defined as at Least 90% Improvement in PASI From Baseline) in Intent to Treat Population at Week 16 (ITT_A) | Week 16 | The PASI is used to evaluate a participant's overall psoriasis disease state that includes the percent of surface area of skin that is affected and the severity of erythema, induration, and desquamation over four body regions (head, upper extremities, trunk, and lower extremities). Scores range from 0 to 72, with higher scores indicating more severe disease. |
| Percentage of Participants Achieving Static Physician Global Assessment (sPGA) 0 or 1 With at Least 2-grade Improvement From Baseline in Intent to Treat Population at Week 16 (ITT_A) | Week 16 | The sPGA is the physician's current assessment of the average thickness, erythema, and scaling of all psoriatic lesions. Scores range from 0 (clear) to 4 (severe). |
| Percentage of Participants Achieving PASI 90 in Intent to Treat Population for Apremilast Non-Responders at Week 52 (ITT_B_NR) | Week 52 | The PASI is used to evaluate a participant's overall psoriasis disease state that includes the percent of surface area of skin that is affected and the severity of erythema, induration, and desquamation over four body regions (head, upper extremities, trunk, and lower extremities). Scores range from 0 to 72, with higher scores indicating more severe disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving PASI 75 (Defined as at Least 75% Improvement in PASI From Baseline) in Intent to Treat Population at Week 16 (ITT_A) | Week 16 | The PASI is used to evaluate a participant's overall psoriasis disease state that includes the percent of surface area of skin that is affected and the severity of erythema, induration, and desquamation over four body regions (head, upper extremities, trunk, and lower extremities). Scores range from 0 to 72, with higher scores indicating more severe disease. |
| Percentage of Participants Achieving PASI 75 in Intent to Treat Population for Apremilast Non-Responders at Week 52 (ITT_B_NR) | Week 52 | The PASI is used to evaluate a participant's overall psoriasis disease state that includes the percent of surface area of skin that is affected and the severity of erythema, induration, and desquamation over four body regions (head, upper extremities, trunk, and lower extremities). Scores range from 0 to 72, with higher scores indicating more severe disease. |
| Percentage of Participants Achieving Static Physician Global Assessment (sPGA) 0 or 1 With at Least 2-grade Improvement From Baseline in Intent to Treat Population for Apremilast Non-Responders at Week 52 (ITT_B_NR) | Week 52 | The sPGA is the physician's current assessment of the average thickness, erythema, and scaling of all psoriatic lesions. Scores range from 0 (clear) to 4 (severe). |
Countries
Canada, Germany, Israel, Poland, United States
Participant flow
Recruitment details
A total of 352 participants were enrolled from 48 sites across 5 countries including Canada, Germany, Israel, Poland, and the United States.
Pre-assignment details
Period A: participants were randomized in a 1:2 ratio to risankizumab (RZB) or apremilast (APR). Period B: participants receiving RZB were continued up to Week 52; participants receiving APR were re-randomized in a 1:1 ratio to receive either RZB or APR (with the option to receive RZB as rescue) up to Week 52. Rerandomization was stratified by Psoriasis Area and Severity Index (PASI) 75 response (responder, non-responder) at Week 16.
Participants by arm
| Arm | Count |
|---|---|
| Period A: APR Apremilast 30 mg orally BID up to Week 16 | 234 |
| Period A: RZB Risankizumab 150 mg as a single SC injection at Baseline (Day 1) and Week 4. | 118 |
| Total | 352 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Period A (Baseline to Week 16) | Lost to Follow-up | 3 | 0 | 0 | 0 | 0 | 0 |
| Period A (Baseline to Week 16) | Other, Not Specified | 6 | 0 | 0 | 0 | 0 | 0 |
| Period A (Baseline to Week 16) | Withdrawal by Subject | 9 | 0 | 0 | 0 | 0 | 0 |
| Period B (Week 16 to Week 52) | Lost to Follow-up | 0 | 6 | 4 | 6 | 0 | 0 |
| Period B (Week 16 to Week 52) | Other, Not Specified | 0 | 38 | 19 | 18 | 4 | 7 |
| Period B (Week 16 to Week 52) | Withdrawal by Subject | 0 | 5 | 13 | 2 | 3 | 0 |
Baseline characteristics
| Characteristic | Period A: RZB | Total | Period A: APR |
|---|---|---|---|
| Age, Continuous | 45.5 years STANDARD_DEVIATION 13.63 | 46.0 years STANDARD_DEVIATION 14.04 | 46.2 years STANDARD_DEVIATION 14.27 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 30 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 111 Participants | 322 Participants | 211 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 26 Participants | 14 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 14 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 98 Participants | 307 Participants | 209 Participants |
| Sex: Female, Male Female | 42 Participants | 121 Participants | 79 Participants |
| Sex: Female, Male Male | 76 Participants | 231 Participants | 155 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 234 | 0 / 118 | 0 / 116 | 0 / 97 | 0 / 102 | 0 / 48 |
| other Total, other adverse events | 101 / 234 | 24 / 118 | 36 / 116 | 27 / 97 | 31 / 102 | 15 / 48 |
| serious Total, serious adverse events | 4 / 234 | 1 / 118 | 8 / 116 | 2 / 97 | 3 / 102 | 0 / 48 |
Outcome results
Primary
Percentage of Participants Achieving PASI 90 in Intent to Treat Population for Apremilast Non-Responders at Week 52 (ITT_B_NR)
The PASI is used to evaluate a participant's overall psoriasis disease state that includes the percent of surface area of skin that is affected and the severity of erythema, induration, and desquamation over four body regions (head, upper extremities, trunk, and lower extremities). Scores range from 0 to 72, with higher scores indicating more severe disease.
Time frame: Week 52
Population: ITT\_B\_NR Population: participants randomized to APR at Baseline who failed to achieve PASI 75 at Week 16 and were re-randomized to APR or RZB in Period B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period A: APR | Percentage of Participants Achieving PASI 90 in Intent to Treat Population for Apremilast Non-Responders at Week 52 (ITT_B_NR) | 2.6 percentage of participants |
| Period A: RZB | Percentage of Participants Achieving PASI 90 in Intent to Treat Population for Apremilast Non-Responders at Week 52 (ITT_B_NR) | 72.3 percentage of participants |
p-value: <0.00195% CI: [59.5, 80]Chi-squared
Primary
Percentage of Participants Achieving Psoriasis Area Severity Index (PASI) 90 (Defined as at Least 90% Improvement in PASI From Baseline) in Intent to Treat Population at Week 16 (ITT_A)
The PASI is used to evaluate a participant's overall psoriasis disease state that includes the percent of surface area of skin that is affected and the severity of erythema, induration, and desquamation over four body regions (head, upper extremities, trunk, and lower extremities). Scores range from 0 to 72, with higher scores indicating more severe disease.
Time frame: Week 16
Population: ITT\_A Population: all participants randomized in Period A
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period A: APR | Percentage of Participants Achieving Psoriasis Area Severity Index (PASI) 90 (Defined as at Least 90% Improvement in PASI From Baseline) in Intent to Treat Population at Week 16 (ITT_A) | 5.1 percentage of participants |
| Period A: RZB | Percentage of Participants Achieving Psoriasis Area Severity Index (PASI) 90 (Defined as at Least 90% Improvement in PASI From Baseline) in Intent to Treat Population at Week 16 (ITT_A) | 55.9 percentage of participants |
p-value: <0.00195% CI: [41.3, 60.1]Cochran-Mantel-Haenszel
Primary
Percentage of Participants Achieving Static Physician Global Assessment (sPGA) 0 or 1 With at Least 2-grade Improvement From Baseline in Intent to Treat Population at Week 16 (ITT_A)
The sPGA is the physician's current assessment of the average thickness, erythema, and scaling of all psoriatic lesions. Scores range from 0 (clear) to 4 (severe).
Time frame: Week 16
Population: ITT\_A Population: all participants randomized in Period A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period A: APR | Percentage of Participants Achieving Static Physician Global Assessment (sPGA) 0 or 1 With at Least 2-grade Improvement From Baseline in Intent to Treat Population at Week 16 (ITT_A) | 18.4 percentage of participants |
| Period A: RZB | Percentage of Participants Achieving Static Physician Global Assessment (sPGA) 0 or 1 With at Least 2-grade Improvement From Baseline in Intent to Treat Population at Week 16 (ITT_A) | 75.4 percentage of participants |
p-value: <0.00195% CI: [47.7, 66]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving PASI 75 (Defined as at Least 75% Improvement in PASI From Baseline) in Intent to Treat Population at Week 16 (ITT_A)
The PASI is used to evaluate a participant's overall psoriasis disease state that includes the percent of surface area of skin that is affected and the severity of erythema, induration, and desquamation over four body regions (head, upper extremities, trunk, and lower extremities). Scores range from 0 to 72, with higher scores indicating more severe disease.
Time frame: Week 16
Population: ITT\_A Population: all participants randomized in Period A
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period A: APR | Percentage of Participants Achieving PASI 75 (Defined as at Least 75% Improvement in PASI From Baseline) in Intent to Treat Population at Week 16 (ITT_A) | 18.8 percentage of participants |
| Period A: RZB | Percentage of Participants Achieving PASI 75 (Defined as at Least 75% Improvement in PASI From Baseline) in Intent to Treat Population at Week 16 (ITT_A) | 84.7 percentage of participants |
p-value: <0.00195% CI: [57.6, 73.9]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving PASI 75 in Intent to Treat Population for Apremilast Non-Responders at Week 52 (ITT_B_NR)
The PASI is used to evaluate a participant's overall psoriasis disease state that includes the percent of surface area of skin that is affected and the severity of erythema, induration, and desquamation over four body regions (head, upper extremities, trunk, and lower extremities). Scores range from 0 to 72, with higher scores indicating more severe disease.
Time frame: Week 52
Population: ITT\_B\_NR Population: participants randomized to APR at Baseline who failed to achieve PASI 75 at Week 16 and were re-randomized to APR or RZB in Period B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period A: APR | Percentage of Participants Achieving PASI 75 in Intent to Treat Population for Apremilast Non-Responders at Week 52 (ITT_B_NR) | 11.5 percentage of participants |
| Period A: RZB | Percentage of Participants Achieving PASI 75 in Intent to Treat Population for Apremilast Non-Responders at Week 52 (ITT_B_NR) | 83.1 percentage of participants |
p-value: <0.00195% CI: [60.9, 82.3]Chi-squared
Secondary
Percentage of Participants Achieving Static Physician Global Assessment (sPGA) 0 or 1 With at Least 2-grade Improvement From Baseline in Intent to Treat Population for Apremilast Non-Responders at Week 52 (ITT_B_NR)
The sPGA is the physician's current assessment of the average thickness, erythema, and scaling of all psoriatic lesions. Scores range from 0 (clear) to 4 (severe).
Time frame: Week 52
Population: ITT\_B\_NR Population: participants randomized to APR at Baseline who failed to achieve PASI 75 at Week 16 and were re-randomized to APR or RZB in Period B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period A: APR | Percentage of Participants Achieving Static Physician Global Assessment (sPGA) 0 or 1 With at Least 2-grade Improvement From Baseline in Intent to Treat Population for Apremilast Non-Responders at Week 52 (ITT_B_NR) | 7.7 percentage of participants |
| Period A: RZB | Percentage of Participants Achieving Static Physician Global Assessment (sPGA) 0 or 1 With at Least 2-grade Improvement From Baseline in Intent to Treat Population for Apremilast Non-Responders at Week 52 (ITT_B_NR) | 77.1 percentage of participants |
p-value: <0.00195% CI: [58.6, 80.2]Chi-squared