Concomitant Longitudinal Evaluation of Adalimumab With Methotrexate in the Real World: the CLEAR Study
Condition: Psoriasis
MeSH terms: Psoriasis
Intervention: Adalimumab; Methotrexate
Intervention description: Administered by subcutaneous injection every other week.; Methotrexate was provided as 2.5 mg tablets for oral administration.
Intervention MeSH terms: Adalimumab; Methotrexate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: methotrexate; adalimumab; biologic; psoriasis; Tumor necrosis factor (TNF)-α inhibitor

Summary:

      The purpose of this study is to determine the safety and efficacy of the use of the
      combination therapy adalimumab (ADA) every other week (EOW) with methotrexate (MTX) in
      suboptimal responders to ADA monotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subjects who have been on ADA monotherapy (40 mg eow or greater) for at least 16 weeks
             but who in the opinion of the Investigator have shown a sub-optimal response to
             treatment and have a Physician's Global Assessment (PGA) of ≥ 3 and a Psoriasis Area
             Severity Index (PASI) of ≥ 5; or Subjects who after an initial positive response to
             ADA monotherapy (40 mg eow or greater) have failed to maintain an optimal level of
             response, based on the opinion of the Investigator, and have a PGA of ≥ 3 and a PASI
             of ≥ 5;

          2. Subjects who are receiving 40 mg ADA once weekly must be on ADA 40 mg eow for 8 weeks
             prior to screening;

          3. Subjects with at least a 6 month history of chronic plaque psoriasis;

          4. Subjects greater than or equal to 18 years of age;

          5. If female, subject is either not of childbearing potential, defined as postmenopausal
             for at least 1 year or surgically sterile or is of childbearing potential and is
             practicing birth control;

          6. The results of the serum pregnancy test performed during the Screening Period and
             urine pregnancy test performed at the Baseline Visit must be negative;

          7. Subject is judged to be in good general health as determined by the Principal
             Investigator;

          8. Subjects must be evaluated for latent tuberculosis (TB) infection;

          9. Subjects must be able and willing to provide written informed consent and comply with
             the requirements of the study protocol;

         10. Subjects must be willing and able to self-administer subcutaneous (SC) injections or
             have a qualified person available to administer SC injections.

        Exclusion Criteria:

          1. Subject has any contraindications to MTX or ADA;

          2. Subject has a previous failed response or poor tolerance to ADA;

          3. Subject has a poorly controlled medical condition which, in the opinion of the
             Investigator, would put the subject at risk by participation in the study;

          4. Subject has a history of clinically significant hematologic, renal or liver disease;

          5. Subject has a history of neurologic symptoms suggestive of central nervous system
             (CNS) demyelinating disease and/or diagnosis of central demyelinating disease;

          6. Subject has evidence of dysplasia or history of malignancy (including lymphoma and
             leukemia) other than a successfully treated non-metastatic cutaneous squamous cell or
             basal cell carcinoma or localized carcinoma in situ of the cervix;

          7. Subject has a history of listeriosis, histoplasmosis, untreated TB, persistent chronic
             infections, or recent active infections requiring hospitalization or treatment with
             intravenous (iv) anti-infectives within 30 days or oral anti-infectives within 14 days
             prior to the Baseline visit;

          8. Subject is known to have immune deficiency, history of human immunodeficiency virus
             (HIV) or is immunocompromised;

          9. Subject currently uses or plans to use anti-retroviral therapy at any time during the
             study;

         10. Female subject who is pregnant or breast-feeding or considering becoming pregnant
             during the study or for 150 days after the last dose of study medication;

         11. Subject has a history of clinically significant drug or alcohol usage in the last year
             or cannot maintain an alcohol intake of 30 g a day or less throughout the study (one
             standard drink is defined as 180 mL/6 oz (approx. 10 g) of wine, 360 mL/12 oz (approx.
             15 g) of regular beer, or 45 mL/1.5 oz (approx. 10 g) of spirits;

         12. Screening clinical laboratory analyses show any of the following abnormal laboratory
             results:

               -  Aspartate transaminase (AST) or alanine transaminase (ALT) > 2x the upper limit
                  of normal (ULN);

               -  Serum total bilirubin > 1.5 mg/dL (> 26 micromol/L), except for subjects with
                  Gilbert's Syndrome;

               -  Creatinine > 1.5 mg/dL (133 micromol/L) in subjects ≤ 65 years old and > upper
                  limit of normal range in subjects > 65;

               -  Positive Hepatitis B or C serology indicative of previous or current infection.

         13. Subject is considered by the Investigator, for any reason, to be an unsuitable
             candidate for the study;

         14. The following treatments are prohibited for all subjects during the study:

               -  Phototherapy (ultraviolet A with psoralen [PUVA] within 4 weeks of the Baseline
                  Visit and/or ultraviolet B (UVB) within 2 weeks of the Baseline Visit);

               -  Other biologic therapies (including any other anti-tumor necrosis factor [TNF])
                  within 4 weeks of the Baseline Visit;

               -  Any investigational agents of chemical or biologic nature within a minimum of 30
                  days or 5 half-lives (whichever is longer) of the drug prior to the Baseline
                  visit ;

               -  Any other systemic drug therapies for psoriasis within 4 weeks of the Baseline
                  Visit;

               -  Oral or injectable corticosteroids, new prescription topical therapies, or
                  changes in the concentration of current prescription topical therapies (including
                  corticosteroids) that are being used, within 2 weeks of the Baseline Visit.
                  Subjects may continue using previously prescribed topical therapies (including
                  corticosteroids) during the study.

         15. Prior exposure to biologics that have a potential or known association with
             progressive multifocal leukoencephalopathy (PML), i.e., natalizumab (Tysabri®) or
             rituximab (Rituxan®);

         16. Subjects with any active viral infection that based on the investigator's clinical
             assessment makes the subject an unsuitable candidate for the study;