A Safety and Efficacy Study of Ustekinumab in Patients With Plaque Psoriasis Who Have Had an Inadequate Response to Methotrexate
Condition: Psoriasis
MeSH terms: Psoriasis
Intervention: Ustekinumab; Methotrexate
Intervention description: Patients weighting ≤ 100 kg will receive ustekinumab 45 mg at Weeks 0, 4 and 16. Patients who achieve a PASI 75 response at Week 28 and 40 will continue receiving ustekinumab 45 mg at Week 28 and 40. Patients who fail to achieve PASI 75 response at Week 28 will receive ustekinumab 90 mg at Week 28 and 40. Patients who achieve a PASI 75 response at Week 28, but fail to achieve PASI 75 response at Week 40 will receive ustekinumab 90 mg at Week 40. Patients > 100 kg will receive ustekinumab 90 mg at Weeks 0, 4, 16, 28 and 40, regardless of achievement of PASI 75 response. Consideration will be given to discontinuing treatment in these patients if they show no response at Week 28.; Gradual reduction of methotrexate therapy over the 4 week period after Week 0. The methotrexate dose reduction regime will depend on the dose of methotrexate at screening. All patients will stop methotrexate regardless of the final dose after 4 overlapping weeks. The last dose of methotrexate will be given within the 7 day period before the second dose of ustekinumab.
Intervention MeSH terms: Methotrexate; Ustekinumab
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 490.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Psoriasis; Ustekinumab; Stelara; Methotrexate; Biologic

Summary:

      This purpose of this study is to assess the safety of ustekinumab in psoriasis patients who
      receive ustekinumab following an inadequate response to methotrexate therapy. The study will
      provide information for doctors on how to manage the transfer from methotrexate to the
      biologic agent ustekinumab. The study is designed to compare two methods of transferring
      patients from methotrexate to ustekinumab. The two methods being compared are discontinuation
      of methotrexate with immediate initiation of ustekinumab versus initiation of ustekinumab
      with overlap and gradual dose reduction of methotrexate over 4 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients should have diagnosis of plaque-type psoriasis for at least 6 months prior to
             first administration of study agent (patients with concurrent psoriatic arthritis may
             be enrolled)

          -  Moderate-to-severe psoriasis scored as PASI >= 10 at screening and at the time of
             first administration of ustekinumab

          -  Should currently receive (and have been receiving for at least 8 weeks directly prior
             to screening) systemic therapy with methotrexate at a dose of at least 10 mg/week but
             not exceeding 25 mg/week, with an inadequate response to this treatment (due to either
             efficacy or tolerability) and, in the judgment of the treating physician and patient,
             a treatment change is needed

          -  Women should take adequate birth control measures throughout the study and must agree
             to continue to use such birth control measures and not to become pregnant or plan to
             become pregnant for at least 15 weeks after the last dose of ustekinumab and for at
             least 6 months after the last dose of methotrexate

          -  Men must be using adequate birth control measures whilst receiving methotrexate and
             for 6 months after the last dose of methotrexate

        Exclusion Criteria:

          -  Patients should not have non-plaque forms of psoriasis (eg, erythrodermic, guttate, or
             pustular)

          -  Should currently (and within 12 months) not receive ciclosporin, fumarates, PUVA,
             etanercept, efalizumab, infliximab, adalimumab or alefacept or other biologic or
             systemic therapy (and other therapy as indicated in the protocol)

          -  Women who are pregnant, breastfeeding, or planning pregnancy (both men and women)
             while enrolled in the study

          -  Have previously failed treatment with any therapeutic agent directly targeted at
             reducing IL-12 or IL-23, including, but not limited to, ustekinumab and ABT-874

          -  Active or latent Tuberculosis or other chronic or recurrent infectious disease

          -  Known history of lymphoproliferative disease

          -  Known malignancy or history of malignancy