Official Title: “An Open-Label, Randomized Efficacy and Safety Study of Infliximab Versus Methotrexate in the Treatment of Moderate to Severe Psoriasis”

This is a Phase 3b, randomized, parallel-group, multicenter, active-controlled, open-label study of the efficacy and safety of infliximab compared with methotrexate in the treatment of moderate to severe psoriasis in adults who were diagnosed with moderate to severe plaque-type psoriasis for at least 6 months prior to screening (subjects with concurrent psoriatic arthritis may also be enrolled).

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: May 2008

Intervention(s) in this Clinical Trial

• Drug: infliximab
  • The infliximab dose will be prepared according to the subject's weight (5 mg/kg). Each IV infusion will be administered over a period of not less than 2 hours. The infusion must be given via a separate line using the administration set with a 1.2 micron filter. Subjects will be infused at Weeks 0, 2, 6, 14, and 22.
• Drug: methotrexate
  • Methotrexate will be supplied as 2.5 mg tablets. Subjects are to take 15 mg/week orally for the first 6 weeks of the study. Subjects will be advised to take their MTX as a single dose (weekly) on the same day of the week. If subjects randomized to MTX 15 mg/week experience a <25% reduction in PASI score at Week 6 (Visit 4) as compared with Baseline, their MTX dose will be increased to 20 mg/week. Subjects will be treated for 22 weeks.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Infliximab 100 mg
  • P04271 Directions for administration (to be reconstituted as directed and infused, over a period of not less than 2 hours with an in-line, sterile, nonpyrogenic, low-protein-binding filter [pore size of 1.2 micron or less]). Storage requirements (store in a refrigerator between 2°C and 8°C [36° F to 46°F]). Expiration date Batch/FMR number
• Active Comparator: Methotrexate 2.5 mg
  • P04271 Directions for administration (to be administered orally once per week as directed by the investigator) Storage requirements (store at room temperature) Expiration date Batch/FMR number

Primary Measures

• PASI75 response rate at Week 16 (PASI75 is defined as the proportion of subjects achieving a 75% improvement in PASI from Baseline to Week 16).
  • Time Frame: 16 weeks
    Safety Issue?: No

Secondary Measures

• PASI75 response rate at Week 26.
  • Time Frame: 26 weeks
    Safety Issue?: No
• The proportion of subjects achieving a Physician's Global Assessment (PGA) score of cleared (0) or minimal (1) at Weeks 16 and 26.
  • Time Frame: 16 and 26 weeks
    Safety Issue?: No

Inclusion Criteria:

• Adult male and female subjects (>= 18 to 75 years of age) with a diagnosis of moderate to severe plaque-type psoriasis for at least 6 months prior to study screening (subjects with concurrent psoriatic arthritis may also be enrolled).
• Subjects must be eligible for phototherapy or systemic therapy for their psoriasis and must have a Baseline Psoriasis Area and Severity Index (PASI) score of 12 or greater and have at least 10% of their total body surface area (BSA) involved at Baseline.
• Subjects must agree to avoid prolonged sun exposure and avoid use of tanning booths or other ultraviolet light sources during the study.
• Subjects must also meet the tuberculosis (TB) eligibility assessment and screening criteria as follows: Have no history of latent or active TB prior to screening; 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; within 1 month prior to the first administration of study medication, either have negative diagnostic TB test results (defined as 2 negative tuberculin skin tests) OR have a newly identified positive diagnostic TB test result (defined as at least 1 positive tuberculin skin tests) during screening in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated either prior to or simultaneously with the first administration of study medication.
• Subjects must have had a chest x-ray (posterior-anterior and lateral) within 3 months prior to Screening with no evidence of malignancy, infection, fibrosis, or current or old active TB.
• Specific parameters must also be met with regard to screening laboratory test results and liver enzymes in order to be eligible to participate in the study.

Exclusion Criteria:

• Subjects who have non-plaque forms of psoriasis, current drug-induced psoriasis, are pregnant, nursing, or planning pregnancy;
• Subjects previously treated with MTX or infliximab; subjects who are taking specific drugs within the specified time frame prior to Baseline as follows: any therapeutic agent targeted at reducing TNF or any biologic, live virus or bacterial vaccinations within 3 months; any systemic medications or treatments that could affect psoriasis or PASI evaluations, or any systemic immunosuppressants or lithium within 4 weeks; any topical medications or treatments that could affect psoriasis or PASI evaluations within 2 weeks. The only allowed topical treatments for psoriasis are shampoos (containing tar or salicylic acid only) and topical moisturizers. Subjects should not use these topical agents during the morning prior to a study visit. Non-medicated shampoos may be used on the morning of a visit.
• Subjects with poor health, including concomitant congestive heart failure (CHF);
• history of chronic or recurrent infectious disease, as specified; human immunodeficiency virus, hepatitis B, or hepatitis C; demyelinating disease or symptoms suggestive of multiple sclerosis or optic neuritis; systemic lupus erythematosus; or who have had serious infections (eg, hepatitis, pneumonia, or pyelonephritis], or who have been hospitalized or received intravenous (IV) antibiotics, or who had an opportunistic infection (eg, cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB), or a transplanted organ within specified time frames; or other conditions as specified in the protocol.
• Subjects who have used any investigational drugs within 4 weeks of Screening, who are participating in other clinical studies, staff or family members of study staff are excluded from participation in the study.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Schering-Plough

Overall Clinical Trial Officials and Contacts

Christian Antoni, M.D. Study Director Schering-Plough  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00251641

Study ID Number: P04271

ClinicalTrials.gov Identifier: NCT00251641

Health Authority: Austria: Federal Ministry for Health and Women