A Phase III, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Comparative Study of Abatacept or Infliximab in Combination with Methotrexate in Controlling Disease Activity in Subjects with Rheumatoid Arthritis Having an Inadequate Clinical Response to Methotrexate

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2004-000922-59-DK
• Date of registration: 01/12/2004
• Prospective Registration: Yes
• Primary sponsor: Bristol Myers Squibb International Corporation
• Public title: A Phase III, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Comparative Study of Abatacept or Infliximab in Combination with Methotrexate in Controlling Disease Activity in Subjects with Rheumatoid Arthritis Having an Inadequate Clinical Response to Methotrexate
• Scientific title: A Phase III, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Comparative Study of Abatacept or Infliximab in Combination with Methotrexate in Controlling Disease Activity in Subjects with Rheumatoid Arthritis Having an Inadequate Clinical Response to Methotrexate
• Date of first enrolment: 02/02/2005
• Target sample size: 675
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-000922-59
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Placebo arm for 6 months. If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Czech Republic, Denmark, Spain, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
* Subject is willing to participate in the study and signed the informed consent.
* Subjects must meet the criteria of the American Rheumatism Association (1987) for
the diagnosis of rheumatoid arthritis and the American College of Rheumatology
(1991) functional Classes I, II, or III. (Refer to protocol appendices 1 and 2.)
* Subjects must have been taking methotrexate for at least 3 months at a weekly dose of at least 15 mg, and at a stable dose for 28 days prior to treatment (Day 1)
* Men and women, ages 18 = 75 years old. Men and Women of childbearing potential are eligible if they are practicing effective contraceptive measures.
* Methotrexate alone: Subjects who are treated only with methotrexate will not require washout.
* Methotrexate plus other DMARDs: Subjects who are treated with methotrexate in
combination with another anti-rheumatic treatment (DMARD) will require washout
of the other DMARD.
* Drug stabilization requirements (except methotrexate)
a) All DMARDs (except methotrexate) should be discontinued at least 28 days prior
to treatment (Day 1).
i) In the case of leflunomide, the subject can be washed out with cholestyramine
according to manufacturer recommendations.
b) Oral corticosteroid treatment must have been reduced to the equivalent of 10 mg
prednisone daily for 28 days and stabilized for at least 25 out of 28 days prior to
treatment (Day 1).
For Subjects Receiving Methotrexate Alone:
At randomization (Day 1), subjects must have the following disease activity:
a) 10 or more swollen joints (66 joint count) and
b) 12 or more tender joints (68 joint count) and
c) C-reactive protein (CRP) = 1 mg/dL (Result used from screening visit)
For Subjects Receiving Other DMARDs Plus Methotrexate:
At screening visit, subjects must have the following disease activity:
a) 6 or more swollen joints (66 joint count) and
b) 8 or more tender joints (68 joint count) and
c) No restriction on CRP
IN ADDITION
All subjects who are receiving other DMARDs plus methotrexate therapy at the screening visit must undergo a 28 day washout period of their other anti-rheumatic treatment (DMARD) (other than methotrexate).
After washout at randomization (Day 1), subjects must have the following disease
activity:

a) 10 or more swollen joints (66 joint count) and
b) 12 or more tender joints (68 joint count) and
c) C reactive protein (CRP) = 1 mg/dL. (Result used from Day -3 visit).
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 (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
* WOCBP who are unwilling or unable to use an acceptable method to avoid
pregnancy for the entire study period and for up to 10 weeks after the last infusion of abatacept
* Any previous or current medical conditions that are contraindications to the use of
TNF blocking agents. (Please refer to Appendix 11 and 12 Remicade Labels)
* Subjects who have previously received treatment with an approved biologic RA
therapy (Infliximab, Etanercept, Anakinra, Adalimumab).
* Subjects who have failed more than 3 oral DMARDs.
* Subjects with active vasculitis of a major organ system (except for subcutaneous
rheumatoid nodules).
* Current symptoms of severe, progressive, or uncontrolled renal, hepatic,
hematological, gastrointestinal, pulmonary, cardiac, neurological, or cerebral disease.
* Female subjects, who have not had age and/or risk factor appropriate breast cancer screening or who have had a breast cancer screening study that is suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations
* Subjects with a history of cancer within the last five years (other than non-melanoma skin cell cancers cured by local resection). Existing non-melanoma skin cell cancers must be removed prior to dosing.
* Subjects with active tuberculosis (TB) requiring treatment within the previous
3 years. Subjects with a positive PPD at screening will not be eligible for the study
unless active TB infection has been ruled out, they have initiated treatment for latent
TB for at least 4 weeks prior to dosing of study drug, and they have a negative chest
x-ray at enrollment.
* Hepatitis B surface antigen-positive subjects.
* Hepatitis C antibody-positive subjects who are also RIBA-positive or PCR-positive.
* Subjects with any of the following laboratory values:
• Hgb < 8.5 g/dL.
• WBC < 3,000/mm3 (3 x 109/L)
• Platelets < 100,000/mm3 (100 x 109/L).
• Serum creatinine > 2 times upper limit of normal.
• Serum ALT or AST > 2 times upper limit of normal.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid Arthrithis, Nos

Intervention(s)

Product Name: Abatacept
Product Code: BMS-188667
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Abatacept
CAS Number: 332348-12-6
Current Sponsor code: BMS-188667
Other descriptive name: CTLA4Ig
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous use

Trade Name: Remicade
Product Name: Remicade
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Infliximab
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): The primary end point will be the comparison of abatacept versus placebo for changes from baseline to 6 months (Day 197) in the DAS28.

Main Objective: To demonstrate that the abatacept in combination with methotrexate will demonstrate a greater reduction in disease activity than placebo in combination with methotrexate as measured by the disease activity score (DAS28) at 6 months (Day 197).

Secondary Objective: * To demonstrate that infliximab in combination with methotrexate will demonstrate a greater reduction in disease activity than placebo in combination with methotrexate as measured by the disease activity score (DAS28) at 6 months.
* Compare the reduction in disease activity over time as measured by the DAS28 area under the curve (DAS28AUC) over 12 months in subjects receiving abatacept versus infliximab in combination with methotrexate.
* Assess the change in physical function and the subject’s health-related quality of life as measured by the disability index of the HAQ and the SF-36 questionnaire
respectively, in subjects receiving placebo, abatacept, or infliximab in combination
with methotrexate at 6 months and 12 months
* Determine the proportion of subjects treated with abatacept or infliximab at
12 months who demonstrate a good, moderate or no response according to the EULAR response criteria.
(see protocol for additional secondary objectives).

Secondary ID(s)

2004-000922-59-SE

IM101-043