Psoriasis
Conditions
Keywords
Risankizumab, Psoriasis, Plaque Psoriasis
Brief summary
The primary objective of this study was to evaluate the safety and efficacy of risankizumab (150 mg/mL) administered by prefilled syringe (PFS) for the treatment of adult participants with moderate to severe plaque psoriasis.
Detailed description
This was a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the safety and efficacy of risankizumab 150 mg/mL formulation in PFS in adult participants with moderate to severe plaque psoriasis. The study included a 30-day screening period, a 28-week treatment period with study visits at Weeks 0, 4, 16 and 28, and a subsequent follow-up telephone call at approximately 20 weeks after the last dose of study drug. Study drug dosing consisted of 3 self-administered, subcutaneous (SC) doses on Weeks 0, 4, and 16. Dosing on Week 4 was self-administered at home.
Interventions
DRUGRisankizumab
Risankizumab 150 mg (150 mg/mL) in prefilled syringes, self-administered subcutaneously
DRUGPlacebo solution for risankizumab
Placebo solution in prefilled syringes, self-administered subcutaneously
Sponsors
AbbVie
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
* Participant has diagnosis of chronic plaque psoriasis for at least 6 months before the baseline visit. * Participant meets following disease activity criteria: * Stable moderate to severe chronic plaque psoriasis, defined as greater than or equal to 10% body surface area (BSA) psoriasis involvement, static physician global assessment (sPGA) score of greater than or equal to 3, and Psoriasis Area Severity Index (PASI) greater than or equal to 12 at Screening and baseline visit. * Candidate for systemic therapy as assessed by the investigator.
Exclusion criteria
* Participant has history of active skin disease other than psoriasis that could interfere with the assessment of psoriasis. * Participant has history of erythrodermic psoriasis, generalized or localized pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new onset guttate psoriasis. * Participant has previous exposure to risankizumab.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Psoriasis Area Severity Index (PASI) 90 at Week 16 | At Week 16 | The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI90 is defined as at least a 90% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at Week 16) / PASI score at Baseline \* 100. |
| Percentage of Participants Achieving Static Physician Global Assessment (sPGA) of Clear or Almost Clear at Week 16 | At Week 16 | The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema, induration, and scaling of psoriatic lesions are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean \>0, \<1.5; Mild (2) = mean ≥1.5, \<2.5; Moderate (3) = mean ≥2.5, \<3.5; and Severe (4) = mean ≥3.5. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Psoriasis Area Severity Index (PASI) 100 at Week 16 | At Week 16 | The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI100 is defined as a 100% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at Week 16) / PASI score at Baseline \* 100. |
| Percentage of Participants Achieving Static Physician Global Assessment (sPGA) of Clear at Week 16 | At Week 16 | The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema, induration, and scaling of psoriatic lesions are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean \>0, \<1.5; Mild (2) = mean ≥1.5, \<2.5; Moderate (3) = mean ≥2.5, \<3.5; and Severe (4) = mean ≥3.5. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Psoriasis Area Severity Index (PASI) Score up to Week 16 | Baseline, Week 4, and Week 16 | The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked.The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. Negative values indicate an improvement from baseline. |
Countries
Puerto Rico, United States
Participant flow
Pre-assignment details
Intent-to-treat (ITT) population: all randomized participants
Participants by arm
| Arm | Count |
|---|---|
| Risankizumab Subcutaneous (SC), self-administered 150 mg doses of risankizumab at Weeks 0, 4, and 16 | 105 |
| Placebo Subcutaneous (SC), self-administered doses of placebo solution at Weeks 0, 4, and 16 | 52 |
| Total | 157 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lack of Efficacy | 0 | 11 |
| Overall Study | Lost to Follow-up | 8 | 2 |
| Overall Study | Withdrew consent | 5 | 6 |
Baseline characteristics
| Characteristic | Risankizumab | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 49.3 years STANDARD_DEVIATION 15.14 | 48.8 years STANDARD_DEVIATION 15.47 | 49.1 years STANDARD_DEVIATION 15.2 |
| Body Surface Area (BSA) Psoriasis Involvement at Baseline | 28.343 Percentage of body surface area affected STANDARD_DEVIATION 16.4139 | 28.160 Percentage of body surface area affected STANDARD_DEVIATION 18.4868 | 28.282 Percentage of body surface area affected STANDARD_DEVIATION 17.0689 |
| Duration of Plaque Psoriasis | 20.91 years STANDARD_DEVIATION 13.837 | 15.82 years STANDARD_DEVIATION 11.753 | 19.22 years STANDARD_DEVIATION 13.363 |
| Prior Use of Systemic Biologic for Psoriasis 0 | 58 Participants | 29 Participants | 87 Participants |
| Prior Use of Systemic Biologic for Psoriasis ≥1 | 47 Participants | 23 Participants | 70 Participants |
| Psoriasis Area and Severity Index (PASI) Score at Baseline | 21.529 units on a scale STANDARD_DEVIATION 9.5975 | 21.060 units on a scale STANDARD_DEVIATION 10.2563 | 21.373 units on a scale STANDARD_DEVIATION 9.7901 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 12 Participants | 4 Participants | 16 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 87 Participants | 44 Participants | 131 Participants |
| Sex: Female, Male Female | 46 Participants | 24 Participants | 70 Participants |
| Sex: Female, Male Male | 59 Participants | 28 Participants | 87 Participants |
| Static Physician Global Assessment (sPGA) Score at Baseline Score of 3 | 86 Participants | 46 Participants | 132 Participants |
| Static Physician Global Assessment (sPGA) Score at Baseline Score of 4 | 19 Participants | 6 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 105 | 0 / 52 |
| other Total, other adverse events | 0 / 105 | 0 / 52 |
| serious Total, serious adverse events | 1 / 105 | 0 / 52 |
Outcome results
Primary
Percentage of Participants Achieving Psoriasis Area Severity Index (PASI) 90 at Week 16
The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI90 is defined as at least a 90% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at Week 16) / PASI score at Baseline \* 100.
Time frame: At Week 16
Population: Intent-to-treat (ITT) population: all randomized participants; those with missing data were imputed as non-responders
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Risankizumab | Percentage of Participants Achieving Psoriasis Area Severity Index (PASI) 90 at Week 16 | 62.9 percentage of participants |
| Placebo | Percentage of Participants Achieving Psoriasis Area Severity Index (PASI) 90 at Week 16 | 3.8 percentage of participants |
Comparison: The variable was analyzed using the Chi-square test. Both null hypotheses corresponding to the co-primary endpoints must be rejected simultaneously under a two-sided significance level of 0.05.p-value: <0.00195% CI: [48.4, 69.6]Chi-squared
Primary
Percentage of Participants Achieving Static Physician Global Assessment (sPGA) of Clear or Almost Clear at Week 16
The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema, induration, and scaling of psoriatic lesions are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean \>0, \<1.5; Mild (2) = mean ≥1.5, \<2.5; Moderate (3) = mean ≥2.5, \<3.5; and Severe (4) = mean ≥3.5.
Time frame: At Week 16
Population: Intent-to-treat (ITT) population: all randomized participants; those with missing data were imputed as non-responders
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Risankizumab | Percentage of Participants Achieving Static Physician Global Assessment (sPGA) of Clear or Almost Clear at Week 16 | 78.1 percentage of participants |
| Placebo | Percentage of Participants Achieving Static Physician Global Assessment (sPGA) of Clear or Almost Clear at Week 16 | 9.6 percentage of participants |
Comparison: The variable was analyzed using the Chi-square test. Both null hypotheses corresponding to the co-primary endpoints must be rejected simultaneously under a two-sided significance level of 0.05.p-value: <0.00195% CI: [57.2, 79.7]Chi-squared
Secondary
Percentage of Participants Achieving Psoriasis Area Severity Index (PASI) 100 at Week 16
The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI100 is defined as a 100% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at Week 16) / PASI score at Baseline \* 100.
Time frame: At Week 16
Population: Intent-to-treat (ITT) population: all randomized participants; those with missing data were imputed as non-responders
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Risankizumab | Percentage of Participants Achieving Psoriasis Area Severity Index (PASI) 100 at Week 16 | 38.1 percentage of participants |
| Placebo | Percentage of Participants Achieving Psoriasis Area Severity Index (PASI) 100 at Week 16 | 1.9 percentage of participants |
Comparison: The ranked secondary efficacy endpoints at Week 16 were to be tested between the risankizumab and placebo treatment groups among the ITT Population in a hierarchical order only if the null hypotheses for both primary endpoints had been rejected.p-value: <0.00195% CI: [26.2, 46.2]Chi-squared
Secondary
Percentage of Participants Achieving Static Physician Global Assessment (sPGA) of Clear at Week 16
The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema, induration, and scaling of psoriatic lesions are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean \>0, \<1.5; Mild (2) = mean ≥1.5, \<2.5; Moderate (3) = mean ≥2.5, \<3.5; and Severe (4) = mean ≥3.5.
Time frame: At Week 16
Population: Intent-to-treat (ITT) population: all randomized participants; those with missing data were imputed as non-responders
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Risankizumab | Percentage of Participants Achieving Static Physician Global Assessment (sPGA) of Clear at Week 16 | 39.0 percentage of participants |
| Placebo | Percentage of Participants Achieving Static Physician Global Assessment (sPGA) of Clear at Week 16 | 1.9 percentage of participants |
Comparison: The ranked secondary efficacy endpoints at Week 16 were to be tested between the risankizumab and placebo treatment groups among the ITT Population in a hierarchical order only if the null hypotheses for both primary endpoints and for the first secondary endpoint had been rejected.p-value: <0.00195% CI: [27.1, 47.2]Chi-squared
Other Pre-specified
Percent Change From Baseline in Psoriasis Area Severity Index (PASI) Score up to Week 16
The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked.The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. Negative values indicate an improvement from baseline.
Time frame: Baseline, Week 4, and Week 16
Population: Intent-to-treat (ITT) population: all randomized participants with a non-missing baseline measurement and at least one post-baseline value
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Risankizumab | Percent Change From Baseline in Psoriasis Area Severity Index (PASI) Score up to Week 16 | Week 4 | -50.62 percent change from Baseline |
| Risankizumab | Percent Change From Baseline in Psoriasis Area Severity Index (PASI) Score up to Week 16 | Week 16 | -89.36 percent change from Baseline |
| Placebo | Percent Change From Baseline in Psoriasis Area Severity Index (PASI) Score up to Week 16 | Week 4 | -14.48 percent change from Baseline |
| Placebo | Percent Change From Baseline in Psoriasis Area Severity Index (PASI) Score up to Week 16 | Week 16 | -29.39 percent change from Baseline |
Comparison: Risankizumab vs placebo at Week 4~Mixed-effect Model Repeat Measurements (MMRM): The repeated measures analysis was conducted using a mixed model including the baseline value and observed measurements at all post-baseline visits. The mixed model included the categorical fixed effects of treatment, visit and treatment-by-visit interaction as covariates.p-value: <0.00195% CI: [-45.936, -26.346]Mixed-effect Model Repeat Measurements
Comparison: Risankizumab vs placebo at Week 16~Mixed-effect Model Repeat Measurements (MMRM): The repeated measures analysis was conducted using a mixed model including the baseline value and observed measurements at all post-baseline visits. The mixed model included the categorical fixed effects of treatment, visit and treatment-by-visit interaction as covariates.p-value: <0.00195% CI: [-70.501, -49.439]Mixed-effect Model Repeat Measurements