Psoriasis
Conditions
Keywords
Psoriasis, CNTO 1275, Etanercept, Immune diorder, Skin disorder
Brief summary
The purpose of this study is to compare the efficacy and safety of CNTO 1275 to etanercept in patients with moderate to severe plaque psoriasis.
Detailed description
This is a multicenter, randomized (study medication assigned by chance), active-controlled, parallel, 3-arm study. Patients will be randomly (allocation to treatments available by chance) assigned in 3:5:5 ratio to receive one of three treatments groups. The three treatment groups are: Group 1 - CNTO 1275 45 mg dosing at weeks 0 and 4, Group 2 - CNTO 1275 90 mg dosing at weeks 0 and 4, Group 3 - Etanercept 50 mg two times per week through week 12. The total duration for each participant will be up to 64 weeks (approximately 16 months). The active-controlled portion of the study is from Week 0 to Week 12 during which the efficacy and safety of etanercept and 2 dose levels of CNTO 1275 will be evaluated. Treatment after Week 12 is dependent on Physician's Global Assessment (PGA) response at Week 12 and initial treatment assignment. Patients will receive 2 subcutaneous injections of CNTO 1275 (either 45 or 90 mg doses) or twice weekly injections of etanercept during the first twelve weeks of the study. Patients may receive two additional doses of CNTO 1275 (either 45 or 90 mg doses) up to week 44.
Interventions
DRUGCNTO 1275 45 mg
Type=exact number, number=45, unit=mg, form=injection, route=subcutaneous
DRUGCNTO 1275 90 mg
Type=exact number, number=90, unit=mg, form=injection, route=subcutaneous
DRUGEtanercept 50 mg
Type=exact number, number=50, unit=mg, form=injection, route=subcutaneous
Sponsors
Centocor, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
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 prior to the study * Have plaque-type psoriasis covering at least 10 percentage of total body surface area * Have a Psoriasis Area and Severity Index (PASI) score of 12 or greater and a Physician's Global Assessment (PGA) score of 3 or greater at the time of the first administration of study drug * Must be suitable for phototherapy or systemic treatment for psoriasis * Have failed to respond to or have condition which prevents use of cyclosporine, methotrexate (MTX) or psoralen plus ultraviolet light A (PUVA)
Exclusion criteria
* Currently have nonplaque forms of psoriasis * Have current drug-induced psoriasis * Have used any therapeutic agent targeted at reducing interleukin-12 (IL-12) or IL-23 (Interleukins are the substance produced by body in immunological disease like psoriasis) * Have received phototherapy or any systemic medications/treatments that could affect psoriasis or PASI evaluation (including, but not limited to, oral or injectable corticosteroids, retinoids, 1,25 dihydroxy vitamin D3 and analogues, psoralens, sulfasalazine, hydroxyurea, or fumaric acid derivatives) within 4 weeks of the first administration of study agent * Have used a biologic within the previous 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving a Greater Than or Equal to 75 Percentage Improvement From Baseline in Psoriasis Area and Severity Index (PASI 75) Score at Week 12 | Baseline and Week 12 | Number of participants achieving greater than or equal to 75 percentage improvement from baseline in Psoriasis Area and Severity Index (PASI) at Week 12. PASI is the widely used tool for the measurement of severity of psoriasis. 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. The scale ranges from 0 (best) -72 (worst). Baseline visit refers to Week 0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Physician's Global Assessment (PGA) of Cleared or Minimal at Week 12 | Week 12 | Number of participants achieving a physician global assessment (PGA) (0-5) of cleared or minimal at Week 12. The PGA is 7-point scale used in clinical trial of various diseases. In this the physician checks the state of the disease and gives them score from 0 (clear) to 5 (severe). |
| Number of Participants Achieving a Greater Than or Equal to 90 Percentage Improvement From Baseline in Psoriasis Area and Severity Index (PASI 90) Score at Week 12 | Baseline and Week 12 | Number of participants achieving greater than or equal to 90 percentage improvement from baseline in Psoriasis Area and Severity Index (PASI) at Week 12. PASI is the widely used tool for the measurement of severity of psoriasis. 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. The scale ranges from 0 (best) -72 (worst). |
| Difference in Psoriasis Area Severity Index Between Week 12 and That Achieved 12 Weeks After Retreatment (Week R12) | Up to Week 52. Retreatment may occur anytime between Week 16 and Week 40 depending on time of losing PGA response. Hence end of 12 weeks of retreatment would be between Week 28 and Week 52, inclusive. | The difference between the PASI score at Week 12 and that achieved after 12 weeks of retreatment. The PASI is the widely used tool for the measurement of severity of psoriasis. 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. The scale ranges from 0 (best) -72 (worst). |
Participant flow
Recruitment details
903 partcipants received either ustekinumab (CNTO 1275) or etanercept at 67 sites in North America and Europe.
Participants by arm
| Arm | Count |
|---|---|
| Group I: Etanercept Participants received Etanercept 50 mg twice weekly through Week 12. Participants with PGA greater than or equal to 3 at Week 12 received ustekinumab 90 mg at Week 16 and 20. Participants with PGA leeser than or equal to 2 at Week 12 received ustekinumab 90 mg upon losing PGA response (PGA greater than or equal to 3) and 4 weeks after. | 347 |
| Group II: Ustekinumab 45 mg Participants received ustekinumab 45 mg at Weeks 0, 4 . Participants with PGA greater than or equal to 3 at Week 12 received ustekinumab 45 mg at Week 16. Participants with PGA lesser than or equal to 2 at Week 12 received ustekinumab 45 mg upon losing PGA response (PGA greater than or equal to 3) and 4 weeks after. | 209 |
| Group III: Ustekinumab 90 mg Participants received ustekinumab 90 mg at Weeks 0, 4 . Participants with PGA greater than or equal to 3 at Week 12 received ustekinumab 90 mg at Week 16. Participants with PGA lesser than or equal to 2 at Week 12 received ustekinumab 90 mg upon losing PGA response (PGA greater than or equal to 3) and 4 weeks after. | 347 |
| Total | 903 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| After Controlled Period | Adverse Event | 0 | 0 | 0 | 9 | 3 | 9 |
| After Controlled Period | Lack of Efficacy | 0 | 0 | 0 | 1 | 0 | 0 |
| After Controlled Period | Lost to Follow-up | 0 | 0 | 0 | 2 | 4 | 6 |
| After Controlled Period | Other | 0 | 0 | 0 | 1 | 0 | 0 |
| Controlled Period | Adverse Event | 5 | 2 | 1 | 0 | 0 | 0 |
| Controlled Period | Lost to Follow-up | 1 | 2 | 2 | 0 | 0 | 0 |
| Controlled Period | Other | 5 | 4 | 2 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Group I: Etanercept | Group II: Ustekinumab 45 mg | Group III: Ustekinumab 90 mg | Total |
|---|---|---|---|---|
| Age Continuous | 45.7 years STANDARD_DEVIATION 13.4 | 45.1 years STANDARD_DEVIATION 12.56 | 44.8 years STANDARD_DEVIATION 12.29 | 45.2 years STANDARD_DEVIATION 12.78 |
| Sex: Female, Male Female | 101 Participants | 76 Participants | 113 Participants | 290 Participants |
| Sex: Female, Male Male | 246 Participants | 133 Participants | 234 Participants | 613 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 |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 154 / 347 | 85 / 209 | 126 / 347 | 60 / 337 | 102 / 295 | 85 / 204 | 164 / 343 |
| serious Total, serious adverse events | 4 / 347 | 4 / 209 | 4 / 347 | 8 / 337 | 10 / 295 | 13 / 204 | 22 / 343 |
Outcome results
Primary
Number of Participants Achieving a Greater Than or Equal to 75 Percentage Improvement From Baseline in Psoriasis Area and Severity Index (PASI 75) Score at Week 12
Number of participants achieving greater than or equal to 75 percentage improvement from baseline in Psoriasis Area and Severity Index (PASI) at Week 12. PASI is the widely used tool for the measurement of severity of psoriasis. 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. The scale ranges from 0 (best) -72 (worst). Baseline visit refers to Week 0.
Time frame: Baseline and Week 12
Population: Intent to treat. All participants randomized were included in the analysis according to the assigned treatment groups. Participants is considered a non- responder if the participant has used any pre-specified prohibited medications or discontinued due to lack of efficacy or has missing data at Week 12.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group I: Etanercept | Number of Participants Achieving a Greater Than or Equal to 75 Percentage Improvement From Baseline in Psoriasis Area and Severity Index (PASI 75) Score at Week 12 | 197 Participants |
| Group II: Ustekinumab 45 mg | Number of Participants Achieving a Greater Than or Equal to 75 Percentage Improvement From Baseline in Psoriasis Area and Severity Index (PASI 75) Score at Week 12 | 141 Participants |
| Group III: Ustekinumab 90 mg | Number of Participants Achieving a Greater Than or Equal to 75 Percentage Improvement From Baseline in Psoriasis Area and Severity Index (PASI 75) Score at Week 12 | 256 Participants |
p-value: <0.001Cochran-Mantel-Haenszel (CMH) chi square
Comparison: Null Hypothesis: No difference between ustekinumab 90 mg or 45 mg and etanercept at an overall significant level of 0.05. Sample Size: Assuming the PASI 75 response rates of ustekinumab 90 mg, 45 mg, etanercept are 65%, 64%, and 50% , respectively, with 325 participants each in the ustekinumab 90 mg and etanercept groups, the power to detect a treatment difference is 97%. With 200 participants in the ustekinumab 45 mg group, the complete power to further detect a treatment difference was 87%.p-value: 0.012Cochran-Mantel-Haenszel (CMH) chi square
Secondary
Difference in Psoriasis Area Severity Index Between Week 12 and That Achieved 12 Weeks After Retreatment (Week R12)
The difference between the PASI score at Week 12 and that achieved after 12 weeks of retreatment. The PASI is the widely used tool for the measurement of severity of psoriasis. 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. The scale ranges from 0 (best) -72 (worst).
Time frame: Up to Week 52. Retreatment may occur anytime between Week 16 and Week 40 depending on time of losing PGA response. Hence end of 12 weeks of retreatment would be between Week 28 and Week 52, inclusive.
Population: Participants who were randomized to ustekinumab, had a PGA score less than or equal to 2 at Week 12, and were retreated upon losing PGA response (PGA greater than or equal to 3).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group I: Etanercept | Difference in Psoriasis Area Severity Index Between Week 12 and That Achieved 12 Weeks After Retreatment (Week R12) | -0.99 Score on a scale | Standard Error 3.799 |
| Group II: Ustekinumab 45 mg | Difference in Psoriasis Area Severity Index Between Week 12 and That Achieved 12 Weeks After Retreatment (Week R12) | -0.30 Score on a scale | Standard Error 4.124 |
Secondary
Number of Participants Achieving a Greater Than or Equal to 90 Percentage Improvement From Baseline in Psoriasis Area and Severity Index (PASI 90) Score at Week 12
Number of participants achieving greater than or equal to 90 percentage improvement from baseline in Psoriasis Area and Severity Index (PASI) at Week 12. PASI is the widely used tool for the measurement of severity of psoriasis. 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. The scale ranges from 0 (best) -72 (worst).
Time frame: Baseline and Week 12
Population: Intent to treat. All randomly assigned participants were included in the analysis according to the assigned treatment groups. A participant is considered a non-responder if the participant has used any pre-specified prohibited medications, discontinued due to lack of efficacy, or had a missing Week 12 PASI score.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group I: Etanercept | Number of Participants Achieving a Greater Than or Equal to 90 Percentage Improvement From Baseline in Psoriasis Area and Severity Index (PASI 90) Score at Week 12 | 80 Participants |
| Group II: Ustekinumab 45 mg | Number of Participants Achieving a Greater Than or Equal to 90 Percentage Improvement From Baseline in Psoriasis Area and Severity Index (PASI 90) Score at Week 12 | 76 Participants |
| Group III: Ustekinumab 90 mg | Number of Participants Achieving a Greater Than or Equal to 90 Percentage Improvement From Baseline in Psoriasis Area and Severity Index (PASI 90) Score at Week 12 | 155 Participants |
p-value: <0.001Cochran-Mantel-Haenszel (CMH) chi square
Comparison: Null Hypothesis: No difference between ustekinumab 90 mg or 45 mg and etanercept at an overall significant level of 0.05.p-value: <0.001Cochran-Mantel-Haenszel (CMH) chi square
Secondary
Number of Participants With Physician's Global Assessment (PGA) of Cleared or Minimal at Week 12
Number of participants achieving a physician global assessment (PGA) (0-5) of cleared or minimal at Week 12. The PGA is 7-point scale used in clinical trial of various diseases. In this the physician checks the state of the disease and gives them score from 0 (clear) to 5 (severe).
Time frame: Week 12
Population: Intent to treat. All randomly assigned 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 or had a missing PGA score.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group I: Etanercept | Number of Participants With Physician's Global Assessment (PGA) of Cleared or Minimal at Week 12 | 170 Participants |
| Group II: Ustekinumab 45 mg | Number of Participants With Physician's Global Assessment (PGA) of Cleared or Minimal at Week 12 | 136 Participants |
| Group III: Ustekinumab 90 mg | Number of Participants With Physician's Global Assessment (PGA) of Cleared or Minimal at Week 12 | 245 Participants |
p-value: <0.001Cochran-Mantel-Haenszel (CMH) chi square
Comparison: Null Hypothesis: No difference between ustekinumab 90 mg or 45 mg and etanercept at an overall significant level of 0.05.p-value: <0.001Cochran-Mantel-Haenszel (CMH) chi square