If you have been told less than one year ago that you have
rheumatoid arthritis, then you may be eligible to participate in an
international 18-month research study of an investigational
combination of medication currently used for rheumatoid
arthritis.
1. Subject is =18 years of age
2. Subject has a diagnosis of RA as defined by the 1987-revised
ACR-c1assification criteria and have a disease duration of less
than 1 year from diagnosis. (see Appendix G).
3. Subject must meet the following three criteria:
a. DAS28 (CRP) > 3.2.
b. At least 6 swollen joints out of 66 assessed.
c. At least 8 tender joints out of 68 assessed.
4. Subject must have an ESR = 28 nun/lh or CRP = 1.5 mg/dL.
5. Subject must fulfill one of the following three criteria:
a. Rheumatoid Factor (RF) positive
b. Have greater than 1 erosion
c. Anti- CCP Antibody positive
6. Female subject is either not of childbearing potential, defined
as postmenopausal (at least 1 year since last menses) or surgically
sterile (bilateral tuba11igation, bilateral oophorectomy or
hysterectomy), or is 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 mine
pregnancy test at Baseline.
8. Subject is judged to be in good general health as determined
by the principal investigator based upon the results of medical
history, laboratory profile, physical examination, chest X-ray
(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 chest X-ray. 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-Guerin (BCG)
vaccination stahls, 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 at least two weeks prior to
administration of study drug; 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
Centers for Disease Control [CDC] recommended preventive therapy
for TB) or per local guidelines. Prophylactic treatment should be
captured on the concomitant medications page in the CRF and in the
source documents. See Appendix D for Centers for Disease Control
(CDC) recommended preventive therapy for TB.
- Subject has documented prophylactic treatment for TB and so
need not repeat this treatment.
A subject will be excluded from the Study if he/she meets any of
the following criteria:
1. Subject has previous exposure to any systemic
anti-TNF therapy (e.g., infliximab or etanercept) including
adalimumab.
2. Subject has been previously treated with> I prior disease
modifying antirheumatic drugs (DMARDs) or prior MTX treatment.
3. Subject has been treated with Intra-articular or parenteral
administration of corticosteroids in the preceding 4 weeks. Inhaled
corticosteroids for stable medical conditions are allowed.
4. Subject has undergone joint surgery within the preceding two
months (at joints to be assessed within the study).
5. Subject has chronic arthritis diagnosed before age 17
years.
6. Subject has a history of an allergic reaction or significant
sensitivity to constituents of study drugs (adalimumab, MTX, or
matching placebo).
7. Subject has been treated with any investigational drug of a
"chemical" nature within one month prior to study entry
(screening visit).
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 or liver
disease (e.g., fibrosis, cirrhosis, hepatitis).
10. Subject has history of neurologic symptoms suggestive of
central nervous system (eNS) demyelinating disease and/or diagnosis
of central demyelinating disease.
11. Subject has history of cancer or Iymphoproliferative 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 oflisteriosis, 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.
13. Subject currently uses or plans to use anti-retroviral
therapy at any time during the study.
14. Subject is known to have immune deficiency, history of HIV
or is immunocompromised.
15. Female subject who is pregnant or breast-feeding or
considering becoming pregnant during the study or for ISO 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
30 g a day or less throughout the study. One standard drink is
defined as 180 m/6 oz (approx. 10 g) of wine, 360 mL/l2 oz (approx.
15 g) of regular beer, or 45 mL/1.5 oz (approx. 10 g) of
spirits.
17. Screening clinical laboratory analyses show any of the
following abnormal laboratory results:
- Aspartate transaminase (AST) or alanine transaminase (ALT)
>1.75x the upper limit of normal (ULN).
- Serum total bilirubin = 1.5 mg/dL (= 26 micromol/L); or
- 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.
18. Subject is considered by the investigator, for any reason,
to be an unsuitable candidate for the study.
If you would like to learn more about participating in this study, please send an e-mail message using the form below.
