Long-Term Effects of Infliximab in the Treatment of Moderate to Severe Psoriasis [Extension of Study P04271, NCT00251641] (P04563)

Study Overview
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Brief Summary
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This is a long-term, randomized, multi-center, open-label study of infliximab treatment in adults with moderate to severe plaque-type psoriasis. This study is the long-term extension of Study P04271 (NCT00251641); Study P04271 is a Phase 3b, randomized, parallel-group, multicenter, open-label, 26-week study comparing the efficacy and safety of infliximab versus methotrexate in the treatment of adult subjects with moderate to severe plaque-type psoriasis. The objectives of this study are to assess the efficacy and safety of long-term maintenance therapy versus intermittent therapy with 5 mg/kg infliximab in a moderate to severe plaque-type psoriasis population. During an interim safety evaluation of the trial, a higher incidence of serious and severe infusion reactions was observed in the intermittent treatment arm, consisting of a re-induction cycle (maximum of 4 infusions at 0, 2, 6 and 14 weeks) after a period of no treatment compared with the maintenance arm (infusions every 8 weeks without an interruption of treatment). Consequently, the sponsor has terminated the trial. The label will be updated to reflect this new information relating to the use of a re-induction regimen with infliximab.

Official Title
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A Long-Term Efficacy and Safety Study of Infliximab in the Treatment of Moderate to Severe Plaque-Type Psoriasis

Conditions
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Psoriasis

Intervention / Treatment
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* Biological: infliximab
* Biological: infliximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have met all inclusion/exclusion criteria in Study P04271 (NCT00251641). Subjects must have been originally randomized to infliximab in Study P04271. Subjects must have completed the full 26 weeks of Study P04271. Subjects must have remained on infliximab for the full 22 weeks of treatment in Study P04271. Subjects must have achieved an improvement in Psoriasis Area and Severity Index (PASI) score >=75% from Baseline of Study P04271 to Week 26 of Study P04271. Subjects must agree to avoid prolonged sun exposure and avoid use of tanning booths or other ultraviolet light sources during the study. Subjects are considered eligible according to the following tuberculosis (TB) criteria: Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination; Have had no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to or simultaneously with the first administration of study medication. Subjects' Baseline (Visit 1) clinical laboratory tests (complete blood count, blood chemistry, and urinalysis) must be within the following parameters: Hemoglobin >=10 g/dL White blood cells >=3.5 x 10^9/L Neutrophils >=1.5 x 10^9/L Platelets >=100 x 10^9/L Serum creatinine <1.5 mg/dL (or <133 umol/L) Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase levels as outlined in Protocol P04563. Total bilirubin <2 x upper limit of normal [Note: If Baseline laboratory tests are not yet available, then the previous laboratory tests from Week 22 of the parent study (Study P04271) should be used for enrollment. When the Baseline laboratory tests become available, the investigator must apply the above parameters to determine a subject's eligibility.] Subjects must be free of any clinically significant disease (other than plaque-type psoriasis or psoriatic arthritis) that would interfere with the study evaluations. Subjects must be willing to give written informed consent and be able to adhere to dose and visit schedules. Women of childbearing potential and all men must be using adequate birth control measures (eg, abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) and must continue using such measures until 6 months after receiving the last infusion of study medication. Female subjects of childbearing potential must have a negative urine pregnancy test at Baseline. Exclusion Criteria: Subjects who have any significant ongoing adverse events (AEs) or AEs from Study P04271 (NCT00251641) that would prohibit further treatment with infliximab at the time of entry. Subjects originally randomized to methotrexate or subjects who received methotrexate at any time during their participation in Study P04271. Subjects who have non-plaque forms of psoriasis (eg, erythrodermic, guttate, or pustular). Subjects who have current drug-induced psoriasis (eg, a new onset of psoriasis or an exacerbation of psoriasis from beta blockers, calcium channel blockers, or lithium). Female subjects who are pregnant, nursing, and both men and women who are planning pregnancy during the study period or during the 6 months after receiving of the last infusion of study medication. Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study. Subjects who are staff personnel directly involved with this study. Subjects who are family members of the investigational study staff.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Maintenance Infliximab<br>Infliximab 5 mg/kg by body weight every 8 weeks | Biological: infliximab<br>* Infliximab maintenance therapy intravenous (IV) infusion every 8 weeks, 5 mg/kg body weight (first infusion at Week 4/Visit 2).<br>* Other names: Remicade;|
| Experimental: Intermittent Infliximab<br>Infliximab 5 mg/kg by body weight at Weeks 0, 2, 6 and 14 following a 50% reduction in Psoriasis Area and Severity Index (PASI) from the Study P04271 Baseline | Biological: infliximab<br>* Infliximab intermittent therapy: Paricipants will receive no infliximab treatment until the Week 26 improvement in PASI from Baseline (original Study P04271 [NCT00251641] Baseline) is reduced by more than 50%. At that time, participants will receive an infliximab infusion, 5 mg/kg body weight. Participants may receive additional infusions at 0, 2, 6, and 14 weeks after the first infusion of the cycle (ie, a maximum of 4 infusions in each infusion cycle) as needed until they respond, defined as a >=75% improvement in PASI from the original Baseline in Study P04271. Subjects will receive no further treatment until they relapse again (ie, improvement in PASI from Baseline is reduced by more than 50%), at which time participants will receive another infusion cycle of up to 4 infusions, as described above. Throughout the study, intermittent treatment infusion cycles will be repeated whenever participants relapse.<br>* Other names: Remicade;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Achieved Psoriasis Area and Severity Index 75 (PASI75) Response at Week 128 | PASI75 defined as the number of participants who achieved a >=75% improvement in Psoriasis Area and Severity Index (PASI) from the original Baseline in Study P04271 (NCT00251641). | 128 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Achieved PASI75 Response at Week 52 | PASI75 defined as the number of participants who achieved a >=75% improvement in PASI from the original Baseline in Study P04271 (NCT00251641) | 52 weeks | 
| Number of Participants Who Achieved PASI75 Response at Week 100 | PASI75 defined as the number of participants who achieved a >=75% improvement in PASI from the original Baseline in Study P04271 (NCT00251641) | 100 Weeks | 
| PASI 6-month Area Under the Curve (AUC); (Time Adjusted Total PASI Score Over the 6 Month Period) | The PASI 6-month AUC is a time adjusted total PASI score over the 6 month (180 days) period. The AUC is a continuous measurement (not a score on a scale); a lower value is considered better and a higher value is considered worse. The weighted average PASI score over 6 months (using all available PASI scores during a 6 month period [from Day 0 to 180 days]) is obtained by using PASI 6-month AUC /180 days. | Day 0 to 180 days | 
| PASI 12-month AUC (Time Adjusted Total PASI Score Over the 12 Month Period) | The PASI 12-month AUC is a time adjusted total PASI score over the 12 month (360 days) period. The AUC is a continuous measurement (not a score on a scale); and a lower value is considered better. The weighted average PASI score over 12 months (using all available PASI scores during a 12 month period [from Day 0 to 360 days]) is is obtained by using PASI 12-month AUC /360 days. | Day 0 to 360 days |