Psoriasis
Conditions
Brief summary
Subjects with moderate-to-severe chronic psoriasis not responding to standard or biologic therapy will be eligible to enroll in this study. Subjects will receive infliximab infusions (5 mg/kg of body weight) at Weeks 0, 2, 6, and 14 followed by a 12-week follow-up period. The efficacy of infliximab will be evaluated by the Psoriasis Area and Severity Index (PASI).
Interventions
BIOLOGICALInfliximab
Infliximab 5 mg/kg of body weight administered as an infusion at Weeks 0, 2, 6 (induction phase), and 14 (maintenance phase).
Sponsors
Centocor, Inc.
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* \>=18 to 75 years of age, of either gender, and of any race. * Psoriasis covering at least 10% of total body surface area (BSA) and PASI \>=12 at Screening and Baseline. * Diagnosis of moderate-to-severe psoriasis at least 6 months prior the screening. * Eligible to infliximab who have failed at least 1 of the following: corticosteroids, methotrexate (MTX), systemic retinoids, cyclosporine, psoralen-ultraviolet A (PUVA), ultraviolet B (UVB) phototherapy, and/or biologics (etanercept or efalizumab). * Eligible according to tuberculosis (TB) eligibility assessment, screening and early detection of reactivation rules. * Chest x-ray within 3 months prior to Screening with no evidence of malignancy, infection, or fibrosis. * Screening and Baseline tests (complete blood count \[CBC\], blood chemistry, and urinalysis) must be within protocol-specified parameters. * Free of significant disease that could interfere with study evaluations. * Willing to give written informed consent and able to adhere to protocol visits and procedures. * Women of childbearing potential and all men must be using adequate birth control and must continue to do so for 6 months after receiving the last dose of study medication. * Females of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline.
Exclusion criteria
* Standard concomitant psoriasis therapies. * Active or latent TB. * History of chronic infectious disease, opportunistic infection, or serious infection within 2 months of enrollment. * History of lymphoproliferative disease. * Malignancy in past 5 years (except treated basal cell carcinoma \[BCC\]). * Treatment with tumor necrosis factor (TNF) antagonists within previous 6 weeks. * Current drug-induced psoriasis. * Females who are pregnant or nursing and females and males who are planning pregnancy within 6 months from the last infusion of infliximab. * Previously treated with infliximab. * Concomitant diagnosis of congestive heart failure (CHF) including medically-controlled asymptomatic subjects. * History of chronic or recurrent infectious disease. * Have or have had a serious infection or have been hospitalized or received intravenous antibiotics for an infection during the 2 months prior to Screening. * Have or have had an opportunistic infection within 6 months prior to Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieve a Greater Than or Equal to 75% Improvement in Psoriasis Area and Severity Index (PASI) Score | 10 weeks | PASI 75 response is defined as participants who achieved at least a 75% improvement in PASI score from Baseline to Week 10. The PASI is a system used for assessing and grading the severity of psoriatic lesions and their responses to therapy. The PASI produces a numeric score that can range from 0 to 72 (the higher the number, the worse the disease). |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Infliximab 5 mg/kg Infliximab 5 mg/kg of body weight administered as an infusion at Weeks 0, 2, 6 (induction phase), and 14 (maintenance phase). | 159 |
| Total | 159 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | Did not return for visit | 3 |
| Overall Study | For reasons different from those above | 4 |
| Overall Study | Lack of Efficacy | 6 |
| Overall Study | Protocol Violation | 7 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Infliximab 5 mg/kg |
|---|---|
| Age, Continuous | 44.15 years STANDARD_DEVIATION 12.8 |
| Sex: Female, Male Female | 40 Participants |
| Sex: Female, Male Male | 119 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 16 / 159 |
| serious Total, serious adverse events | 2 / 159 |
Outcome results
Primary
Number of Participants Who Achieve a Greater Than or Equal to 75% Improvement in Psoriasis Area and Severity Index (PASI) Score
PASI 75 response is defined as participants who achieved at least a 75% improvement in PASI score from Baseline to Week 10. The PASI is a system used for assessing and grading the severity of psoriatic lesions and their responses to therapy. The PASI produces a numeric score that can range from 0 to 72 (the higher the number, the worse the disease).
Time frame: 10 weeks
Population: Intent to Treat Population (ITT): 159 participants out of the 215 enrolled patients who received at least one dose of the study drug.~Per Protocol Population (PP): 138 participants not withdrawn from the study due to major protocol violation and who have received the three infusions of the study drug planned by the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intent to Treat Population | Number of Participants Who Achieve a Greater Than or Equal to 75% Improvement in Psoriasis Area and Severity Index (PASI) Score | 111 Participants |
| Per Protocol Population | Number of Participants Who Achieve a Greater Than or Equal to 75% Improvement in Psoriasis Area and Severity Index (PASI) Score | 111 Participants |