Psoriasis
Conditions
Keywords
Psoriasis, Psoriatic Arthritis, Ustekinumab, CNTO 1275
Brief summary
The purpose of this study is to evaluate the efficacy and safety of Ustekinumab in the treatment of patients with moderate to severe psoriasis in South Korea and Taiwan.
Detailed description
This is phase 3, multicenter, randomized, placebo-controlled double-blind, parallel study of subcutaneous injection of placebo and ustekinumab 45mg in Taiwanese and Korean patients with moderate to severe plaque psoriasis. Ustekinumab is an experimental medicine that is being tested to see if it may be useful in treating moderate to severe psoriasis. The patients will receive either ustekinumab or placebo at week 0 or week 4, and will be followed up through week 36. Patients who randomized (study drug assigned by chance) to placebo will cross over to ustekinumab 45mg group at week 12 and week 16 .The effectiveness of ustekinumab will be compared with placebo treated patients at week 12. Safety information will be collected through week 36. Patients randomized to ustekinumab will receive placebo at week 12 to maintain the blind and additional dose of 45mg at week 16. This study will be conducted in approximately 13 sites in South Korea and Taiwan and will include approximately 120 patients with approximately 60 patients in each country. This study is blinded. This means that neither you nor your study doctor will know in which group you are placed. However, in case of medical emergency, your study doctor can quickly find out which treatment group you are in. You may get either ustekinumab or placebo (which looks like the medicine being studied but has no active ingredients) at the start of the study. All patients in the study will eventually receive Ustekinumab after week 12. Patients assigned to the ustekinumab will receive 45 mg subcutaneously at weeks 0, 4 and 16; and placebo at week 12. Patiens assigned to placebo will receive subcutaneous injections of placebo at weeks 0 and 4; then crossover to 45 mg of ustekinumab at weeks 12 and 16. Duration of study participation up to 36 weeks.
Interventions
DRUGPlacebo - Controlled Period (CP)
Placebo, Weeks 0-12
DRUGUstekinumab 45 mg - CP
Ustekinumab 45 mg, Weeks 0-12
DRUGPlacebo to ustekinumab 45 mg - after CP
Placebo at Weeks 0 and 4, then ustekinumab 45 mg at Week 12 and Week 16
DRUGUstekinumab 45 mg - after CP
Ustekinumab 45 mg at Weeks 0 and 4, then placebo at Week 12 and ustekinumab 45 mg at Week 16
Sponsors
Centocor, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must be of Taiwanese or Korean ancestry living in Taiwan or South Korea, respectively * Have a diagnosis of plaque-type psoriasis at least 6 months prior to first administration of study agent (patients with concurrent psoriatic arthritis may be enrolled) * Have plaque-type psoriasis covering at least 10% of total body surface area at screening and at the time of first study agent administration * PASI score of 12 or greater at the time of screening and at time of first study agent administration * Candidate of phototherapy or systemic treatment of psoriasis (either naïve or history of previous treatment) * Be able to adhere to the study visit schedule and other protocol requirements * Capable of giving informed consent prior to any study related procedures.
Exclusion criteria
* Currently have a non-plaque form of psoriasis * Have current drug-induced psoriasis * Are pregnant or nursing or planning pregnancy (both men and women) while enrolled in the study * Have used any investigational drug within the previous 4 weeks or 5 times the half life of the investigational agent, whichever is longer * Have used any biologic within the previous 3 months or 5 times the half life of the biologic, whichever is longer * Have been hospitalized in the past 3 years for asthma, ever required intubation for treatment of asthma, currently require oral corticosteroids for the treatment of asthma, or required more than one short-term course of oral corticosteroids for asthma within the previous year * Have a history of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Patients Who Achieved at Least a 75% Improvement in PASI (Psoriasis Area and Severity Index) at Week 12 | Week 12 | PASI score can range from 0 (no psoriasis) to 72 (severe psoriasis). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Patients With a Physician's Global Assessment (PGA) Score of Cleared (0) or Minimal (1) at Week 12 | Week 12 | — |
| The Change in Dermatology Life Quality Index (DLQI) From Baseline at Week 12 | Baseline to Week 12 | Scores could range from 0 to 30. A lower DLQI score represents better quality of life. |
Countries
South Korea, Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo (CP) Controlled period (Week 0-12) - Placebo Group | 60 |
| Ustekinumab 45 mg (CP) Controlled period (Week 0-12) - Ustekinumab 45 mg Group | 61 |
| Total | 121 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| After Controlled Period | Adverse Event | 0 | 0 | 0 | 1 |
| Controlled Period | Adverse Event | 3 | 0 | 0 | 0 |
| Controlled Period | Lack of Efficacy | 2 | 1 | 0 | 0 |
| Controlled Period | Other | 0 | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | Ustekinumab 45 mg (CP) | Total | Placebo (CP) |
|---|---|---|---|
| Age Continuous | 40.9 years STANDARD_DEVIATION 12.66 | 40.6 years STANDARD_DEVIATION 11.4 | 40.4 years STANDARD_DEVIATION 10.06 |
| Region of Enrollment Republic of Korea | 31 participants | 61 participants | 30 participants |
| Region of Enrollment Taiwan | 30 participants | 60 participants | 30 participants |
| Sex: Female, Male Female | 11 Participants | 18 Participants | 7 Participants |
| Sex: Female, Male Male | 50 Participants | 103 Participants | 53 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 | 30 / 60 | 25 / 61 | 18 / 55 | 28 / 59 |
| serious Total, serious adverse events | 2 / 60 | 0 / 61 | 5 / 55 | 2 / 59 |
Outcome results
Primary
The Number of Patients Who Achieved at Least a 75% Improvement in PASI (Psoriasis Area and Severity Index) at Week 12
PASI score can range from 0 (no psoriasis) to 72 (severe psoriasis).
Time frame: Week 12
Population: Participants were analyzed according to the treatment group to which they were randomized, regardless of the treatment they received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | The Number of Patients Who Achieved at Least a 75% Improvement in PASI (Psoriasis Area and Severity Index) at Week 12 | 3 Participants |
| Ustekinumab 45 mg | The Number of Patients Who Achieved at Least a 75% Improvement in PASI (Psoriasis Area and Severity Index) at Week 12 | 41 Participants |
Comparison: Null Hypothesis: No difference between ustekinumab 45 mg and placebo for the primary endpoint at a significance level of 0.05. With 120 subjects (60 in each treatment group), simulation studies were conducted to calculate the power to detect a treatment difference in the primary endpoint between ustekinumab 45 mg group and placebo using a CMH test stratified by baseline weight (\<=65kg vs \> 65 kg). For all the scenarios evaluated, the power was \> 99% at a significance level of 0.05.p-value: <0.001Cochran-Mantel-Haenszel
Secondary
The Change in Dermatology Life Quality Index (DLQI) From Baseline at Week 12
Scores could range from 0 to 30. A lower DLQI score represents better quality of life.
Time frame: Baseline to Week 12
Population: Participants were analyzed according to the treatment group to which they were randomized, regardless of the treatment they received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | The Change in Dermatology Life Quality Index (DLQI) From Baseline at Week 12 | -0.5 Scores on a scale | Standard Deviation 6.51 |
| Ustekinumab 45 mg | The Change in Dermatology Life Quality Index (DLQI) From Baseline at Week 12 | -11.2 Scores on a scale | Standard Deviation 7.07 |
Comparison: Null Hypothesis: No difference between ustekinumab 45 mg and placebo at a significance level of 0.05.p-value: <0.001ANOVA
Secondary
The Number of Patients With a Physician's Global Assessment (PGA) Score of Cleared (0) or Minimal (1) at Week 12
Time frame: Week 12
Population: Participants were analyzed according to the treatment group to which they were randomized, regardless of the treatment they received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | The Number of Patients With a Physician's Global Assessment (PGA) Score of Cleared (0) or Minimal (1) at Week 12 | 5 Participants |
| Ustekinumab 45 mg | The Number of Patients With a Physician's Global Assessment (PGA) Score of Cleared (0) or Minimal (1) at Week 12 | 43 Participants |
Comparison: Null Hypothesis: No difference between ustekinumab 45 mg and placebo at a significance level of 0.05.p-value: <0.001Cochran-Mantel-Haenszel