Psoriasis
Conditions
Keywords
Psoriasis, Plaque-type psoriasis, Guselkumab, Ustekinumab, CNTO 1959, Monoclonal antibody
Brief summary
The purpose of this study is to evaluate the efficacy and safety of guselkumab (CNTO 1959) in the treatment of participants with moderate to severe plaque-type psoriasis (scaly skin rash) who had inadequate response to ustekinumab.
Detailed description
This is a randomized (assignment of study drug by chance), double-blind (participants nor study staff will know the identity of study drugs), multicenter study to evaluate efficacy and safety of guselkumab for the treatment of participants with moderate to severe plaque-type psoriasis who had an inadequate response to ustekinumab. The study will consist of a screening period, open-label and double-blind treatment periods, and a follow-up period. The treatment period will have 2 phases: an open-label treatment phase during which all participants will receive ustekinumab at Weeks 0 and 4 and a blinded treatment phase during which participants with an inadequate Investigator's Global Assessment response (IGA≥2) to ustekinumab at Week 16 will be randomized to receive either guselkumab or ustekinumab through Week 44. Participants with an IGA response of 0 or 1 (cleared or minimal disease) at Week 16 will continue to receive open-label treatment with ustekinumab every 12 weeks through Week 40. All participants will complete a follow-up phase through Week 52 for efficacy and through Week 60 for safety evaluations. The total duration of the study will be approximately 64 weeks (includes a 4-week screening period). Participants' safety will be monitored throughout the study.
Interventions
DRUGUstekinumab
45 mg or 90 mg given by subcutaneous injection at Weeks 0 and 4 for all participants. Participants with an IGA score of 0 or 1 at Week 16 will also receive ustekinumab every 12 weeks (q12w) from Week 16 to Week 40.
DRUGGuselkumab
100 mg given by subcutaneous injection at Weeks 16 and 20 and every 8 weeks (q8w) thereafter through Week 44.
Subcutaneous injection at Weeks 16, 28, and 40 to maintain the blind for participants randomized to treatment with guselkumab.
Subcutaneous injection at Weeks 16 and 20 and q8w thereafter through Week 44 to maintain the blind for participants randomized to treatment with ustekinumab.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Have a diagnosis of plaque-type psoriasis (with or without psoriatic arthritis for at least 6 months before the first administration of study drug * Have a Psoriasis Area and Severity Index (PASI) greater than or equal to (\>=) 12 at Screening and at Baseline * Have an Investigator's Global Assessment (IGA) \>=3 at Screening and at Baseline * Have an involved body surface area (BSA) \>= 10 percent (%) at Screening and at Baseline * Be a candidate for phototherapy or systemic treatment for psoriasis (either naïve or history of previous treatment)
Exclusion criteria
* Has a history or current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances * Has unstable cardiovascular disease, defined as a recent clinical deterioration (example \[eg\], unstable angina, rapid atrial fibrillation) in the last 3 months or a cardiac hospitalization within the last 3 months * Currently has a malignancy or has a history of malignancy within 5 years before Screening (with the exception of a nonmelanoma skin cancer that has been adequately treated with no evidence of recurrence for at least 3 months before the first study drug administration, or cervical carcinoma in situ that has been treated with no evidence of recurrence for at least 3 months before the first study drug administration) * Has previously received guselkumab or ustekinumab
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Visits at Which Participants Achieved an Investigator's Global Assessment (IGA) Response of Cleared (0) or Minimal (1) and at Least a 2 Grade Improvement (From Week 16) From Week 28 Through Week 40 | Week 28 through Week 40 | The IGA documents the investigator's assessment of the participants psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The participants' psoriasis was assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Visits at Which Participants Achieved a Psoriasis Area and Severity Index (PASI) 90 Response From Week 28 Through Week 40 | Week 28 through Week 40 | The PASI is a system used for assessing and grading the severity of psoriatic lesions. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas were assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 to 6, and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that can range from 0 to 72. A higher score indicates more severe disease. A PASI 90 response represents participants who achieved at least a 90 percent improvement from baseline in the PASI score. |
| Number of Visits at Which Participants Achieved an IGA Score of Cleared (0) From Week 28 Through Week 40 | Week 28 through Week 40 | The IGA documents the investigator's assessment of the participants psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The participants' psoriasis was assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4). |
| Percentage of Participants With an Investigator's Global Assessment (IGA) Score of Cleared (0) or Minimal (1) and at Least a 2 Grade Improvement (From Week 16) at Week 28 | Week 28 | The IGA documents the investigator's assessment of the participants psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The participants' psoriasis was assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4). |
Countries
Australia, Canada, Germany, Poland, Russia, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Pre-assignment details
Study consists of 2 periods: Open label run-in (Period 1) and blinded phase (Period 2). Participants were enrolled in open label run-in period only. Participants completed the open label run-in period entered into blinded phase period.
Participants by arm
| Arm | Count |
|---|---|
| Ustekinumab (Open Label Run-in) All participants received ustekinumab 45 milligram (mg) (participants weighing less than or equal to \[\<=\]100 kilogram \[kg\]) or 90 mg (participants weighing \>100 kg) at Weeks 0 and 4. At Week 16, participants with IGA \>=2 were randomized to either switch to guselkumab 100 mg at Weeks 16 and 20 and then every 8 weeks thereafter or continue on ustekinumab every 12 weeks (q12w); participants with an IGA=0 or 1 were to continue to receive open-label ustekinumab q12w. | 871 |
| Total | 871 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Blinded Phase (Week 16 to Week 44) | Completed Safety follow-up | 0 | 1 | 3 | 2 |
| Blinded Phase (Week 16 to Week 44) | Death | 0 | 0 | 0 | 1 |
| Blinded Phase (Week 16 to Week 44) | Lost to Follow-up | 0 | 2 | 3 | 8 |
| Blinded Phase (Week 16 to Week 44) | Other | 0 | 4 | 1 | 15 |
| Blinded Phase (Week 16 to Week 44) | Withdrawal by Subject | 0 | 8 | 19 | 20 |
| Open Label Run-in (Week 0 to Week 16) | Adverse Event | 2 | 0 | 0 | 0 |
| Open Label Run-in (Week 0 to Week 16) | Enrolled but not treated | 1 | 0 | 0 | 0 |
| Open Label Run-in (Week 0 to Week 16) | Lack of Efficacy | 1 | 0 | 0 | 0 |
| Open Label Run-in (Week 0 to Week 16) | Lost to Follow-up | 3 | 0 | 0 | 0 |
| Open Label Run-in (Week 0 to Week 16) | Other | 2 | 0 | 0 | 0 |
| Open Label Run-in (Week 0 to Week 16) | Protocol Violation | 4 | 0 | 0 | 0 |
| Open Label Run-in (Week 0 to Week 16) | Withdrawal by Subject | 6 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Ustekinumab (Open Label Run-in) |
|---|---|
| Age, Categorical <=18 years | 4 Participants |
| Age, Categorical >=65 years | 53 Participants |
| Age, Categorical Between 18 and 65 years | 814 Participants |
| Age, Continuous | 43.1 years STANDARD_DEVIATION 13.21 |
| Region of Enrollment Australia | 19 participants |
| Region of Enrollment Canada | 61 participants |
| Region of Enrollment Germany | 96 participants |
| Region of Enrollment Korea, Republic Of | 29 participants |
| Region of Enrollment Poland | 294 participants |
| Region of Enrollment Russia | 88 participants |
| Region of Enrollment Spain | 24 participants |
| Region of Enrollment Taiwan, Province Of China | 55 participants |
| Region of Enrollment United Kingdom | 11 participants |
| Region of Enrollment United States | 194 participants |
| Sex: Female, Male Female | 305 Participants |
| Sex: Female, Male Male | 566 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 | 80 / 871 | 37 / 135 | 33 / 133 | 60 / 585 |
| serious Total, serious adverse events | 11 / 871 | 9 / 135 | 6 / 133 | 20 / 585 |
Outcome results
Primary
Number of Visits at Which Participants Achieved an Investigator's Global Assessment (IGA) Response of Cleared (0) or Minimal (1) and at Least a 2 Grade Improvement (From Week 16) From Week 28 Through Week 40
The IGA documents the investigator's assessment of the participants psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The participants' psoriasis was assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4).
Time frame: Week 28 through Week 40
Population: Randomized population included all enrolled participants with IGA \>=2 at Week 16 randomly assigned to 1 of the 2 treatment regimens (guselkumab or ustekinumab) at Week 16.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Guselkumab (Randomized) | Number of Visits at Which Participants Achieved an Investigator's Global Assessment (IGA) Response of Cleared (0) or Minimal (1) and at Least a 2 Grade Improvement (From Week 16) From Week 28 Through Week 40 | 1.5 visits | Standard Deviation 1.57 |
| Ustekinumab (Randomized) | Number of Visits at Which Participants Achieved an Investigator's Global Assessment (IGA) Response of Cleared (0) or Minimal (1) and at Least a 2 Grade Improvement (From Week 16) From Week 28 Through Week 40 | 0.7 visits | Standard Deviation 1.26 |
p-value: <0.001Row mean score test
Secondary
Number of Visits at Which Participants Achieved an IGA Score of Cleared (0) From Week 28 Through Week 40
The IGA documents the investigator's assessment of the participants psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The participants' psoriasis was assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4).
Time frame: Week 28 through Week 40
Population: Randomized population included all enrolled participants with IGA \>=2 at Week 16 randomly assigned to 1 of the 2 treatment regimens (guselkumab or ustekinumab) at Week 16.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Guselkumab (Randomized) | Number of Visits at Which Participants Achieved an IGA Score of Cleared (0) From Week 28 Through Week 40 | 0.9 visits | Standard Deviation 1.34 |
| Ustekinumab (Randomized) | Number of Visits at Which Participants Achieved an IGA Score of Cleared (0) From Week 28 Through Week 40 | 0.4 visits | Standard Deviation 1.06 |
p-value: <0.001Row mean score test
Secondary
Number of Visits at Which Participants Achieved a Psoriasis Area and Severity Index (PASI) 90 Response From Week 28 Through Week 40
The PASI is a system used for assessing and grading the severity of psoriatic lesions. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas were assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 to 6, and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that can range from 0 to 72. A higher score indicates more severe disease. A PASI 90 response represents participants who achieved at least a 90 percent improvement from baseline in the PASI score.
Time frame: Week 28 through Week 40
Population: Randomized population included all enrolled participants with IGA \>=2 at Week 16 randomly assigned to 1 of the 2 treatment regimens (guselkumab or ustekinumab) at Week 16.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Guselkumab (Randomized) | Number of Visits at Which Participants Achieved a Psoriasis Area and Severity Index (PASI) 90 Response From Week 28 Through Week 40 | 2.2 visits | Standard Deviation 1.69 |
| Ustekinumab (Randomized) | Number of Visits at Which Participants Achieved a Psoriasis Area and Severity Index (PASI) 90 Response From Week 28 Through Week 40 | 1.1 visits | Standard Deviation 1.53 |
p-value: <0.001Row mean score test
Secondary
Percentage of Participants With an Investigator's Global Assessment (IGA) Score of Cleared (0) or Minimal (1) and at Least a 2 Grade Improvement (From Week 16) at Week 28
The IGA documents the investigator's assessment of the participants psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The participants' psoriasis was assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4).
Time frame: Week 28
Population: Randomized population included all enrolled participants with IGA \>=2 at Week 16 randomly assigned to 1 of the 2 treatment regimens (guselkumab or ustekinumab) at Week 16.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Guselkumab (Randomized) | Percentage of Participants With an Investigator's Global Assessment (IGA) Score of Cleared (0) or Minimal (1) and at Least a 2 Grade Improvement (From Week 16) at Week 28 | 31.1 percentage of participants |
| Ustekinumab (Randomized) | Percentage of Participants With an Investigator's Global Assessment (IGA) Score of Cleared (0) or Minimal (1) and at Least a 2 Grade Improvement (From Week 16) at Week 28 | 14.3 percentage of participants |
p-value: =0.001Cochran-Mantel-Haenszel