Concomitant Longitudinal Evaluation of Adalimumab With Methotrexate in the Real World: the CLEAR Study

Concomitant Longitudinal Evaluation of Adalimumab With Methotrexate in the Real World: the CLEAR Study

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.

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;