A Multi-center, Randomized, Double-blind, Placebo - controlled Study Comparing 80 mg of Adalimumab with Placebo, and Demonstrating the Non-inferiority of Monthly 80 mg Adalimumab Dosing Compared With 40 mg Adalimumab Every Other Week Dosing - M10-261, FINAL 30Nov07

• Conditions: Rheumatoid Arthritis; MedDRA version: 9.1Level: LLTClassification code 10039073Term: Rheumatoid arthritis

• Registration Number: EUCTR2007-005905-23-GB
• Lead Sponsor: Abbott GmbH & Co. KG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-02-15
• Last Update Posted: 17 June 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 424

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 a 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 MTX (PO, SC or intramuscular [IM]), the doses must be stable
for at least 4 weeks prior to Screening blood draw and follow standard
recommendations for MTX treatment (ie according to the packaging insert)
5. If a subject is on a DMARD other than MTX, the subject must discontinue it for at
least 28 days before the Baseline Visit/first dose of investigational product (IP)
(wash-out period).
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 Centers for Disease Control (CDC) recommended
preventive therapy for TB or other local guidelines. Prophylactic treatment
should be captured on the concomitant medications page in the case report
form (CRF) and in the source documents.
? Subject has documented prophylactic treatment for TB and so need not repeat
this treatment.
? Active TB has been ruled out.
10. Subjects must be able and willing to provide written informed consent and comply
with the requirements of this study protocol.
11. Subjects must be able and willing to self-administer SC injections or have a
qualified person available to administer SC injections.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (

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/d
prednisone equivalent are allowed
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 (eg, Rituximab,
Tocilizumab, Abatacept, etc)
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 (eg, severe anemia,
leukopenia, thrombocytopenia), renal, liver disease (eg, fibrosis, cirrhosis,
hepatitis), or 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 laboratory analyses show any of the following abnormal
laboratory results:
? Aspartate transaminase (AST) or alanine transaminase (ALT) >2.0x the upper
limit of normal (ULN).
? Serum total bilirubin > 1.5 mg/d

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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).