Rheumatoid Arthritis MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis
Conditions
Sponsors
Abbott GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject will be eligible for study participation if he/she meets the following criteria: 1. Subject is > 18 years of age. 2. Subject has a diagnosis of RA as defined by the 1987-revised ACR-classification criteria and has disease duration for a minimum of three months. 3. Subject must meet the following two criteria: a. At least 6 swollen joints out of 66 assessed. b. At least 6 tender joints out of 68 assessed 4. If a subject is on a DMARD other than Leflunomide and MTX, the subject must discontinue the DMARD for at least 28 days before the Baseline Visit/first dose of investigational product (IP) (wash-out period). If a subject is on Leflunomide, the patient must have a wash out period of 3 months prior to Baseline, however the subject may be treated with cholestyramine to shorten this period. If a subject is on MTX, further criterion is explained below. 5. MTX treatment: a. With MTX: The subject should be on a stable dose of MTX between 15 mg and 25 mg and route of administration must be maintained (PO, subcutaneous [SC] or intramuscular [IM]), for at least 6 weeks prior to Baseline blood draw. Subjects should be treated with MTX per standard recommendations (i.e. according to the packaging insert). Subjects residing in Germany must be on MTX in order to participate in this trial. b. Without MTX or Previously on MTX: The subjects may be MTX naïve from Baseline blood draw or may have been previously been treated with MTX. If the subject was previously treated with MTX, the MTX dose must have been withdrawn at least 28 days prior to Baseline blood draw. 6. Female subjects either not of childbearing potential, defined as postmenopausal (at least 1 year since last menses) or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or are of childbearing potential and practicing one of the following methods of birth control throughout the study and for 150 days after study completion: ? Condoms, sponge, foams, jellies, diaphragm or intrauterine device (IUD) ? Contraceptives (oral, parenteral, patch) for three months prior to study drug administration) ? A vasectomized partner 7. Female subjects of childbearing potential must have a negative serum pregnancy test at the Screening visit and a negative urine pregnancy test at Baseline/first IP dose. 8. Subject is judged to be in good general health as determined by the Principal Investigator or designee based upon the results of medical history, laboratory profile, physical examination, CXR, and 12-lead electrocardiogram (ECG) performed at Screening. 9. Subjects will be evaluated for latent TB infection with a purified protein derivative (PPD) test and CXR. For this protocol, evidence of latent TB infection is defined as an induration (not erythema) of 5 mm or greater, 48-72 hrs after placement. Subjects who demonstrate evidence of latent TB infection, irrespective of Bacille Calmette - Guérin (BCG) vaccination status, and negative CXR findings for active TB and/or suspicious CXR findings will be allowed to participate in the study provided that one of the following conditions are satisfied; ? Prophylactic treatment is initiated before administration of study drug. In general it is recommended, but not mandated, to start 2 weeks before study drug administration, however the course of prophylaxis need not be completed prior to the onset of study drug. Prophylactic treatment will be according to the United States CDC recommended preventive therapy for TB or othe
Exclusion criteria
Exclusion criteria: Subjects presenting with any of the following will not be included in the study. 1. Subject has previous exposure to any systemic anti-TNF therapy (eg, infliximab, etanercept, certolizumab pegol or golimumab) including adalimumab. 2. Subject has been treated with intra-articular or parenteral administration of corticosteroids in the preceding 4 weeks from Baseline visit/first IP dose. Inhaled corticosteroids for stable medical conditions are allowed. Oral of = 10 mg/day prednisone equivalent are allowed, however should be stable 3 weeks prior to Baseline and there should be no plan to dose adjust the steroids throughout the study 3. Subject has undergone joint surgery within the preceding two months of Screening Visit (at joints to be assessed within the study). 4. Subject has a history of acute inflammatory joint disease of different origin other than RA (eg, seronegative spondyloarthropathy, psoriatic arthritis, Reiter's syndrome, systemic lupus erythematosus or any arthritide with onset prior to age 17 years). 5. Subject has a history of an allergic reaction or significant sensitivity to constituents of study drugs (adalimumab, MTX, or matching placebo). 6. Subject has been treated with any investigational drug of a "chemical" nature within one month prior to Baseline/1st IP dose. 7. Subject has been treated with any investigational biologic agents (e.g., Rituximab, Tocilizumab, Abatacept, etc). Should these biologics become approved, they would be excluded. 8. Subject has a poorly controlled medical condition, such as uncontrolled diabetes, unstable heart disease, congestive heart failure, recent cerebrovascular accidents and any other condition which, in the opinion of the Investigator, would put the subject at risk by participation in the study. 9. Subject has a history of clinically significant hematologic (e.g., severe anemia, leukopenia, thrombocytopenia), renal, liver disease (e.g., fibrosis, cirrhosis, hepatitis), or active gastroenteric ulcer. 10. Subject has history of neurologic symptoms suggestive of central nervous system (CNS) demyelinating disease and/or diagnosis of central demyelinating disease. 11. Subject has history of cancer or lymphoproliferative disease other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix. 12. Subject has a history of listeriosis, histoplasmosis, active 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/first IP dose. 13. Subject currently uses or plans to use anti-retroviral therapy at any time during the study. 14. Subject is known to have any acquired immune deficiency (ie, HIV infection) or untreated congenital immunodeficiency. Abbott Study Designated Physician approval required for specific congenital immunodeficiency cases. 15. 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. 16. 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. 17. Screening clinical l
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the efficacy of 80 mg adalimumab monthly dosing compared with placebo as measured by ACR20 response criteria following 12 weeks of therapy. The study is also designed to demonstrate the non-inferiority of monthly dosing of 80 mg adalimumab compared with dosing of 40 mg adalimumab eow as measured by ACR20 response criteria at Week 12.;Secondary Objective: ;Primary end point(s): The primary efficacy analysis will be a comparison of the response rates according to the ACR20 criteria. The improvement in RA (fulfillment of ACR20 criteria) at Week 12 will be compared to the findings before 1st study drug administration (Baseline). | — |
Countries
Germany, United Kingdom
Outcome results
None listed