Psoriasis
Conditions
Keywords
plaque psoriasis, psoriasis, infliximab, remicade, etanercept, enbrel, psunrise, C0168Z04
Brief summary
The purpose of this study is to test the safety and effectiveness of infliximab in patients with plaque psoriasis who have been receiving the drug etanercept for treatment of their plaque psoriasis for at least four months, without enough improvement in their psoriasis symptoms.
Detailed description
The most common form of psoriasis is plaque-type psoriasis, which is characterized by recurrent flaring of thickened, red, scaly patches of skin. Although psoriasis is usually not life threatening, these physical discomforts combined with the potential psychological effects of the disease may interfere with everyday activities and negatively impact an individual's quality of life. Many therapies are available for psoriasis; however, with limited effectiveness and significant toxicity. Infliximab is an antibody made in a laboratory. Antibodies are proteins that fight other substances in the body that may cause infections or diseases. A substance called tumor necrosis factor (TNF) naturally occurs in the body. TNF is related to the itchy patches of skin (or plaques) of psoriasis. Infliximab stops the TNF from working. Other studies have shown that stopping the TNF may reduce the plaques. To address the unmet medical need for effective chronic therapies, TNFalpha blockers have recently been used to treat patients with moderate to severe plaque psoriasis. Etanercept also works by stopping the TNF, but in a different way than infliximab. This multi-center, open-label study is designed to test whether or not patients with plaque psoriasis who have not responded well to etanercept treatment may benefit from treatment with infliximab. Key effectiveness measurements will include the time to onset of symptom improvement and health-related quality of life. Safety will be assessed throughout the study. Two weeks after their last dose of etanercept, all eligible patients will receive open-label 5 mg/kg infliximab infusions at Weeks 0, 2, 6, 14, and 22.
Interventions
BIOLOGICALinfliximab
Open-label 5 mg/kg infliximab infusions at Weeks 0, 2, 6, 14, and 22.
Sponsors
Centocor Ortho Biotech Services, L.L.C.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Have plaque psoriasis despite at least 4 months of treatment with etanercept per current product labeling * Have psoriatic target lesions that have a PGA score greater than 1 (minimal) at screening * If receiving methotrexate at screening, must have received methotrexate for at least 3 months and at a stable dose of \<= 25 mg/week for at least 4 weeks prior to screening * If receiving cyclosporine at screening, must have received cyclosporine at a stable dose of \<= 5 mg/kg daily for at least 4 weeks prior to screening.
Exclusion criteria
* Have already received infliximab or adalimumab * Have shown a previous immediate hypersensitivity response, including anaphylaxis, to an immunoglobulin product * Have a history of latent or active granulomatous infection, including tuberculosis, histoplasmosis, or coccidioidomycosis, prior to screening * Have a concomitant diagnosis or any history of Congestive Heart Failure * Are pregnant, nursing, or planning pregnancy * Have used systemic corticosteroids within the 4 weeks prior to screening * Have used topical corticosteroids or have initiated treatment with other topical therapies that could affect psoriasis or Psoriasis Area and Severity Index (PASI) evaluation (e.g., tar, anthralin, calcipotriene, tazarotene, methoxsalen) within 2 weeks prior to screening * Have used new systemic agents/treatments, other than methotrexate, that can affect psoriasis including, but not limited to, immunosuppressants and/or psoralen plus ultraviolet A light (PUVA) within the 4 weeks prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Achieve a Physician Global Assessment (PGA) Score of Minimal (1) or Clear (0) | Week 10 | Patients who did not have a PGA score at Week 10 will be treated as not having achieved a PGA score of minimal (1) or clear (0) at Week 10. Specifically, treatment failures prior to Week 10 will be classified as not having a minimal (1) or clear (0). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Achieved Psoriasis Area Activity Index (PASI) 50 Response at Week 10 | Week 10 | A PASI 50 responder is defined as a patient who has achieved at least a 50% improvement in the overall PASI score from baseline. PASI is an index used for assessing and grading the severity of psoriatic lesions and their response to therapy. The PASI produces a numeric score that can range from 0 to 72. A score less than 10 signifies a mixture of mild and moderate disease; a score greater than 10 but less than or equal to 30 signifies moderate disease; and a score greater than 30 signifies severe disease. |
| Number of Patients Achieved Psoriasis Area Activity Index (PASI) 50 Response at Week 26 | Week 26 | — |
Participant flow
Recruitment details
A total of 217 subjects enrolled into the study but 2 subjects did not receive any study medication so they were excluded from analysis.
Participants by arm
| Arm | Count |
|---|---|
| Infliximab Open-label 5 mg/kg infliximab infusions at Weeks 0, 2, 6, 14, and 22. | 215 |
| Total | 215 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 13 |
| Overall Study | Lack of Efficacy | 11 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Withdrawal by Subject | 7 |
Baseline characteristics
| Characteristic | Infliximab |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 16 Participants |
| Age, Categorical Between 18 and 65 years | 198 Participants |
| Age Continuous | 44.4 years STANDARD_DEVIATION 13.32 |
| Sex: Female, Male Female | 78 Participants |
| Sex: Female, Male Male | 137 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 63 / 215 |
| serious Total, serious adverse events | 8 / 215 |
Outcome results
Primary
Number of Patients Who Achieve a Physician Global Assessment (PGA) Score of Minimal (1) or Clear (0)
Patients who did not have a PGA score at Week 10 will be treated as not having achieved a PGA score of minimal (1) or clear (0) at Week 10. Specifically, treatment failures prior to Week 10 will be classified as not having a minimal (1) or clear (0).
Time frame: Week 10
Population: This analysis is based on the evaluable population that includes the all enrolled patients who received at least one infliximab infusion, and had a baseline PGA score greater than 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Infliximab | Number of Patients Who Achieve a Physician Global Assessment (PGA) Score of Minimal (1) or Clear (0) | 138 participants |
Comparison: null hypothesis H0: proportion = 0.30p-value: 0.0595% CI: [0.586, 0.718]exact binomial distribution
Secondary
Number of Patients Achieved Psoriasis Area Activity Index (PASI) 50 Response at Week 10
A PASI 50 responder is defined as a patient who has achieved at least a 50% improvement in the overall PASI score from baseline. PASI is an index used for assessing and grading the severity of psoriatic lesions and their response to therapy. The PASI produces a numeric score that can range from 0 to 72. A score less than 10 signifies a mixture of mild and moderate disease; a score greater than 10 but less than or equal to 30 signifies moderate disease; and a score greater than 30 signifies severe disease.
Time frame: Week 10
Population: Analysis is based on observed mITT (modified Intent to Treat) patients. Treatment failures are classified as not achieving a PASI 50, 75, 90, or 100 response at all visits after the date of treatment failure. For non-treatment failure patients who did not have a PASI score at the visit due to other reasons, will not have data imputed at that visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Infliximab | Number of Patients Achieved Psoriasis Area Activity Index (PASI) 50 Response at Week 10 | 167 participants |
p-value: 0.0595% CI: [0.73, 0.844]exact binomial distribution
Secondary
Number of Patients Achieved Psoriasis Area Activity Index (PASI) 50 Response at Week 26
Time frame: Week 26
Population: This analysis is based on all observed mITT patients. The treatment failures will be classified as not achieving a PASI 50, 75, 90, or 100 response at all visits after the date of treatment failure. For non-treatment failure patients who did not have a PASI score at the visit due to other reasons, their data at that visit will not be imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Infliximab | Number of Patients Achieved Psoriasis Area Activity Index (PASI) 50 Response at Week 26 | 135 participants |
p-value: 0.0595% CI: [0.577, 0.711]exact binomial distribution