Psoriasis
Conditions
Keywords
Psoriasis, CNTO 1275, Ustekinumab, Stelara, Interleukin-12, IL-12, Interleukin-23, IL-23
Brief summary
The purpose of this study is to evaluate the efficacy and safety of initial single and multiple subcutaneous injections of CNTO 1275 in the treatment of patients with moderate to severe plaque psoriasis.
Detailed description
This is a randomized (the study medication is assigned by chance), double blind (neither physician nor patient knows the treatment that the patient receives), parallel-group, multicenter study to determine the effectiveness and safety of two different doses of CNTO 1275 administered subcutaneously one time or as multiple doses as compared with placebo in patients with moderate to severe plaque-type psoriasis (the most common type of psoriasis). The dose of CNTO 1275 will be 45 or 90 mg administered subcutaneously once or as four weekly doses. Patients who inadequately respond to their treatment may receive one additional dose. Patients will be monitored for the safety throughout the study.
Interventions
DRUGUstekinumab
Patients will receive subcutaneous injections of ustekinumab (45 or 90 mg).
DRUGPlacebo
Patients in the placebo group will receive placebo medication.
Sponsors
Centocor, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have had a diagnosis of plaque-type psoriasis at least 6 months * Plaque-type psoriasis covering at least 10% of total body surface areas * Psoriasis area-and-severity index score of 12 or greater * Considered by treating dermatologist to be a candidate for phototherapy or systemic treatment of psoriasis * Women of childbearing potential and all men must agree to use adequate birth control measures * Have no history of latent or active tuberculosis
Exclusion criteria
* Currently have nonplaque forms of psoriasis or drug-induced psoriasis * Women who are pregnant or nursing, or men and women planning pregnancy while enrolled in the study * Patients who have a history of chronic or recurrent infectious disease or who have or have had a serious infection requiring hospitalization or intravenous antibiotics within the previous 2 months * Patients who have or ever have had a nontuberculous mycobacterial infection or opportunistic infection * Patients known to be infected with human immunodeficiency virus, hepatitis B, or hepatitis C * Patients who have current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease * Have any known malignancy or have a history of malignancy within the previous 5 years (with the exception of basal cell carcinoma of the skin that has been treated with no evidence of recurrence)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved Psoriasis Area and Severity Index (PASI) 75% Improvement at Week 12 | Week 12 | Psoriasis Area and Severity Index (PASI)(0 \[ best\] -72 \[worst\]) score at Week 12. This is a test of how bad a person's psoriasis is. The combination of redness, scaling, and thickness, as well as overall body involvement determine the PASI score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved Physician's Global Assessment (PGA) Score of Clear (1) or Excellent (2) at Week 12 | Week 12 | Number of participants achieving a physician global assessment (PGA)(1 \[best\] to 6 \[worst\]) score of clear or excellent at Week 12. The PGA is used to determine the participants psoriasis lesions overall at a given time point. Overall lesions will be graded for induration, erythema, and scaling. The sum of the 3 scales will be divided by 3 to obtain a final PGA score. |
| Number of Participants Who Achieved Psoriasis Area Severity Index (PASI) 75% Improvement at Week 32 | Week 32 | Psoriasis Area and Severity Index (PASI)(0 \[ best\] -72 \[worst\]) score at Week 32 for participants who were not retreated at Week 16. This is a test of how bad a person's psoriasis is. The combination of redness, scaling, and thickness, as well as overall body involvement determine the PASI score. |
| Number of Participants Who Achieved Psoriasis Area Severity Index (PASI) 75% Improvement (0-72) at Week 28 | Week 28 | Psoriasis Area and Severity Index (PASI)(0 \[ best\] -72 \[worst\]) score at Week 28 for participants who were retreated at Week 16. This is a test of how bad a person's psoriasis is. The combination of redness, scaling, and thickness, as well as overall body involvement determine the PASI score. |
Participant flow
Recruitment details
320 participants from 45 sites in North America were randomized to receive either Ustekinumab or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Group I: Placebo Participants received placebo at Weeks 0, 1, 2 and 3. At week 16, all participants received placebo regardless of Physician's Global Assessment (PGA). At week 20, all participants received a single dose of ustekinumab 90 mg. | 64 |
| Group II: Ustekinumab 45 mg Participants received ustekinumab 45 mg at Week 0 followed by placebo at Weeks 1, 2 and 3. At week 16, participants who had a Physician's Global Assessment (PGA) \>=3 received 45 mg ustekinumab and participants with a PGA\<3 received placebo. At week 20, all participants received placebo. | 64 |
| Group III: Ustekinumab 90 mg Participants received ustekinumab 90 mg at Week 0 followed by placebo at Weeks 1, 2 and 3. At week 16, participants who had a Physician's Global Assessment (PGA) \>=3 received 90 mg ustekinumab and participants with a PGA\<3 received placebo. At week 20, all participants received placebo. | 64 |
| Group IV: Ustekinumab 45 mg Weekly for 4 Weeks Participants received ustekinumab 45 mg at Weeks 0, 1, 2 and 3. At week 16, participants who had a Physician's Global Assessment (PGA) \>=3 received 45 mg ustekinumab and participants with a PGA\<3 received placebo. At week 20, all participants received placebo. | 64 |
| Group V: Ustekinumab 90 mg Weekly for 4 Weeks Participants received ustekinumab 90 mg at Weeks 0, 1, 2 and 3. At week 16, participants who had a Physician's Global Assessment (PGA) \>=3 received 90 mg ustekinumab and participants with a PGA\<3 received placebo. At week 20, all participants received placebo. | 64 |
| Total | 320 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 6 | 0 | 2 | 2 |
| Overall Study | Lack of Efficacy | 6 | 2 | 1 | 0 | 1 |
| Overall Study | Lost to Follow-up | 3 | 0 | 0 | 0 | 0 |
| Overall Study | Other | 7 | 2 | 5 | 1 | 3 |
Baseline characteristics
| Characteristic | Group I: Placebo | Group II: Ustekinumab 45 mg | Group III: Ustekinumab 90 mg | Group IV: Ustekinumab 45 mg Weekly for 4 Weeks | Group V: Ustekinumab 90 mg Weekly for 4 Weeks | Total |
|---|---|---|---|---|---|---|
| Age, Continuous Years | 44.0 Years STANDARD_DEVIATION 13.7 | 46.4 Years STANDARD_DEVIATION 14.2 | 45.5 Years STANDARD_DEVIATION 12.7 | 44.5 Years STANDARD_DEVIATION 12.2 | 44.3 Years STANDARD_DEVIATION 13.3 | 44.9 Years STANDARD_DEVIATION 13.2 |
| Sex: Female, Male Female | 18 Participants | 26 Participants | 17 Participants | 25 Participants | 52 Participants | 138 Participants |
| Sex: Female, Male Male | 46 Participants | 38 Participants | 47 Participants | 39 Participants | 12 Participants | 182 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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 36 / 67 | 38 / 63 | 40 / 64 | 31 / 63 | 27 / 62 | 16 / 49 | 19 / 60 | 21 / 61 | 17 / 62 | 11 / 62 |
| serious Total, serious adverse events | 1 / 67 | 3 / 63 | 1 / 64 | 2 / 63 | 3 / 62 | 1 / 49 | 0 / 60 | 2 / 61 | 0 / 62 | 4 / 62 |
Outcome results
Primary
Number of Participants Who Achieved Psoriasis Area and Severity Index (PASI) 75% Improvement at Week 12
Psoriasis Area and Severity Index (PASI)(0 \[ best\] -72 \[worst\]) score at Week 12. This is a test of how bad a person's psoriasis is. The combination of redness, scaling, and thickness, as well as overall body involvement determine the PASI score.
Time frame: Week 12
Population: Intent to treat. All participants randomized were included in the analysis according to the assigned treatment groups. Participant is considered a non- responder if the participant has used any pre-specified prohibited medications or discontinued due to lack of efficacy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group I: Placebo | Number of Participants Who Achieved Psoriasis Area and Severity Index (PASI) 75% Improvement at Week 12 | 1 Participants |
| Group II: Ustekinumab 45 mg | Number of Participants Who Achieved Psoriasis Area and Severity Index (PASI) 75% Improvement at Week 12 | 33 Participants |
| Group III: Ustekinumab 90 mg | Number of Participants Who Achieved Psoriasis Area and Severity Index (PASI) 75% Improvement at Week 12 | 38 Participants |
| Group IV: Ustekinumab 45 mg Weekly for 4 Weeks | Number of Participants Who Achieved Psoriasis Area and Severity Index (PASI) 75% Improvement at Week 12 | 43 Participants |
| Group V: Ustekinumab 90 mg Weekly for 4 Weeks | Number of Participants Who Achieved Psoriasis Area and Severity Index (PASI) 75% Improvement at Week 12 | 52 Participants |
p-value: <0.001Cochran-Mantel-Haenszel chi square test
p-value: <0.001Cochran-Mantel-Haenszel (CMH) chi square
p-value: <0.001Cochran-Mantel-Haenszel (CMH) chi square
Comparison: Null Hypothesis:No difference between any ustekinumab group and placebo at an overall significant level of 0.05. Sample Size: With 300 participants (60 in each treatment group), simulation studies were conducted to calculate the power to detect a treatment difference in primary endpoint between ustekinumab groups and placebo using a CMH test with stratification by baseline weight \[≤ 90kg vs \> 90 kg). For all the scenarios evaluated, the power is \>99% at an overall significance level of 0.05.p-value: <0.01Cochran-Mantel-Haenszel (CMH) chi square
Secondary
Number of Participants Who Achieved Physician's Global Assessment (PGA) Score of Clear (1) or Excellent (2) at Week 12
Number of participants achieving a physician global assessment (PGA)(1 \[best\] to 6 \[worst\]) score of clear or excellent at Week 12. The PGA is used to determine the participants psoriasis lesions overall at a given time point. Overall lesions will be graded for induration, erythema, and scaling. The sum of the 3 scales will be divided by 3 to obtain a final PGA score.
Time frame: Week 12
Population: Participants were included in the analysis according to the assigned treatment groups. Participant is considered a non- responder if the participant has used any pre-specified prohibited medications or discontinued due to lack of efficacy. Other missing data were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group I: Placebo | Number of Participants Who Achieved Physician's Global Assessment (PGA) Score of Clear (1) or Excellent (2) at Week 12 | 0 Participants |
| Group II: Ustekinumab 45 mg | Number of Participants Who Achieved Physician's Global Assessment (PGA) Score of Clear (1) or Excellent (2) at Week 12 | 32 Participants |
| Group III: Ustekinumab 90 mg | Number of Participants Who Achieved Physician's Global Assessment (PGA) Score of Clear (1) or Excellent (2) at Week 12 | 34 Participants |
| Group IV: Ustekinumab 45 mg Weekly for 4 Weeks | Number of Participants Who Achieved Physician's Global Assessment (PGA) Score of Clear (1) or Excellent (2) at Week 12 | 46 Participants |
| Group V: Ustekinumab 90 mg Weekly for 4 Weeks | Number of Participants Who Achieved Physician's Global Assessment (PGA) Score of Clear (1) or Excellent (2) at Week 12 | 53 Participants |
p-value: <0.001Cochran-Mantel-Haenszel (CMH) chi square
p-value: <0.001Cochran-Mantel-Haenszel (CMH) chi square
p-value: <0.001Cochran-Mantel-Haenszel (CMH) chi square
Comparison: Null Hypothesis: No difference between any ustekinumab group and placebo.p-value: <0.001Cochran-Mantel-Haenszel (CMH) chi square
Secondary
Number of Participants Who Achieved Psoriasis Area Severity Index (PASI) 75% Improvement (0-72) at Week 28
Psoriasis Area and Severity Index (PASI)(0 \[ best\] -72 \[worst\]) score at Week 28 for participants who were retreated at Week 16. This is a test of how bad a person's psoriasis is. The combination of redness, scaling, and thickness, as well as overall body involvement determine the PASI score.
Time frame: Week 28
Population: Participants were included in the analysis according to the assigned treatment groups. Participant is considered a non- responder if the participant has used any pre-specified prohibited medications or discontinued due to lack of efficacy. Other missing data were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group I: Placebo | Number of Participants Who Achieved Psoriasis Area Severity Index (PASI) 75% Improvement (0-72) at Week 28 | 29 Participants |
| Group II: Ustekinumab 45 mg | Number of Participants Who Achieved Psoriasis Area Severity Index (PASI) 75% Improvement (0-72) at Week 28 | 8 Participants |
| Group III: Ustekinumab 90 mg | Number of Participants Who Achieved Psoriasis Area Severity Index (PASI) 75% Improvement (0-72) at Week 28 | 18 Participants |
| Group IV: Ustekinumab 45 mg Weekly for 4 Weeks | Number of Participants Who Achieved Psoriasis Area Severity Index (PASI) 75% Improvement (0-72) at Week 28 | 8 Participants |
| Group V: Ustekinumab 90 mg Weekly for 4 Weeks | Number of Participants Who Achieved Psoriasis Area Severity Index (PASI) 75% Improvement (0-72) at Week 28 | 3 Participants |
Secondary
Number of Participants Who Achieved Psoriasis Area Severity Index (PASI) 75% Improvement at Week 32
Psoriasis Area and Severity Index (PASI)(0 \[ best\] -72 \[worst\]) score at Week 32 for participants who were not retreated at Week 16. This is a test of how bad a person's psoriasis is. The combination of redness, scaling, and thickness, as well as overall body involvement determine the PASI score.
Time frame: Week 32
Population: Participants were included in the analysis according to the assigned treatment groups. Participant is considered a non- responder if the participant has used any pre-specified prohibited medications or discontinued due to lack of efficacy. Other missing data were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group I: Placebo | Number of Participants Who Achieved Psoriasis Area Severity Index (PASI) 75% Improvement at Week 32 | 1 Particpants |
| Group II: Ustekinumab 45 mg | Number of Participants Who Achieved Psoriasis Area Severity Index (PASI) 75% Improvement at Week 32 | 8 Particpants |
| Group III: Ustekinumab 90 mg | Number of Participants Who Achieved Psoriasis Area Severity Index (PASI) 75% Improvement at Week 32 | 13 Particpants |
| Group IV: Ustekinumab 45 mg Weekly for 4 Weeks | Number of Participants Who Achieved Psoriasis Area Severity Index (PASI) 75% Improvement at Week 32 | 15 Particpants |
| Group V: Ustekinumab 90 mg Weekly for 4 Weeks | Number of Participants Who Achieved Psoriasis Area Severity Index (PASI) 75% Improvement at Week 32 | 31 Particpants |