Clinical trial NCT00251641: The Effects of Infliximab Versus Methotrexate in the Treatment of Moderate to Severe Psoriasis (Study P04271AM2)(COMPLETED)
Official title: An Open-Label, Randomized Efficacy and Safety Study of Infliximab Versus Methotrexate in the Treatment of Moderate to Severe Psoriasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Psoriasis
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2005-11-10
Enrollment: 868
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 3b, randomized, parallel-group, multicenter, active-controlled, open-label study of the efficacy and safety of infliximab compared with methotrexate (MTX) 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).


Eligibility criteria: 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 tumor necrosis factor (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 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.

Primary outcomes:
measure: Psoriasis Area and Severity Index 75 (PASI75) Response at Week 16.
timeFrame: 16 weeks
Secondary outcomes:
measure: PASI75 Response at Week 26
timeFrame: 26 weeks
measure: Proportion of Participants Who Achieved a Physician's Global Assessment (PGA) Score of Cleared or Minimal at Week 16
timeFrame: 16 weeks
measure: Proportion of Participants Who Achieved a PGA Score of Cleared or Minimal at Week 26
timeFrame: 26 weeks
Other outcomes:
Locations:
Study officials:
References:
citation: Barker J, Hoffmann M, Wozel G, Ortonne JP, Zheng H, van Hoogstraten H, Reich K. Efficacy and safety of infliximab vs. methotrexate in patients with moderate-to-severe plaque psoriasis: results of an open-label, active-controlled, randomized trial (RESTORE1). Br J Dermatol. 2011 Nov;165(5):1109-17. doi: 10.1111/j.1365-2133.2011.10615.x.