Long-Term Effects of Infliximab in the Treatment of Moderate to Severe Psoriasis [Extension of Study P04271, NCT00251641] (P04563)
Condition: Psoriasis
MeSH terms: Psoriasis
Intervention: infliximab; infliximab
Intervention description: Infliximab maintenance therapy
intravenous (IV) infusion every 8 weeks, 5 mg/kg body weight (first infusion at Week 4/Visit 2).; 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.
Intervention MeSH terms: Infliximab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 441.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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.