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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 1 May 2012
Main ID:  EUCTR2004-005102-68-ES
Date of registration: 17/06/2005
Prospective Registration: Yes
Primary sponsor: Bristol-Myers Squibb International Corporation
Public title: A Phase III, Multi-Center, Open Label Study to Evaluate the Efficacy, Tolerability and Safety of Abatacept (BMS-188667) in Subjects with Active Rheumatoid Arthritis on Background Non-Biologic DMARDs Who Have An Inadequate Response to Anti-TNF Therapy and Have Limited Therapeutic Options. Protocol Version 4.0 including Protocol amendment 2 + Pharmacogenetic Amendment 1.
Scientific title: A Phase III, Multi-Center, Open Label Study to Evaluate the Efficacy, Tolerability and Safety of Abatacept (BMS-188667) in Subjects with Active Rheumatoid Arthritis on Background Non-Biologic DMARDs Who Have An Inadequate Response to Anti-TNF Therapy and Have Limited Therapeutic Options. Protocol Version 4.0 including Protocol amendment 2 + Pharmacogenetic Amendment 1.
Date of first enrolment: 16/08/2005
Target sample size: 750
Recruitment status: Authorised-recruitment may be ongoing or finished
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-005102-68
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: no Randomised: no Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no  
Phase: 
Countries of recruitment
Belgium Czech Republic Germany Ireland Italy Spain United Kingdom
Contacts
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Key inclusion & exclusion criteria
Inclusion criteria:
1) 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. (see Appendices 1 and 2 of the protocol)
2) Rheumatoid Arthritis for greater than 1 year from the time of the initial diagnosis of
RA.
3) Subjects with RA who are currently receiving or previously received an anti-TNF
therapy at an approved labeled dose for at least 3 months, but had in the
investigator’s opinion, an inadequate efficacy response to therapy. Subjects who
discontinue or discontinued an anti-TNF therapy due to intolerance or safety will be
considered as anti-TNF therapy failures at any time point after they have received
their first dose of anti-TNF therapy.
4) Men and women (not nursing and not pregnant) at least 18 years of age. Men, and women of child bearing potential are eligible if they are practicing effective
contraceptive measures.
-Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study and for up to 10 weeks after the last infusion of abatacept in such a manner that the risk of pregnancy is minimized.
-WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity
25 IU/L or equivalent units of HCG) within 48 hours prior to the start of study
medication.
-Male subjects must be using an adequate method of contraception throughout the study for up to 10 weeks after the last infusion of abatacept that the risk of pregnancy to their partner is minimized.
5)Drug stabilization requirements*:
a) All other background non-biologic DMARD therapy must be stabilized for a
28 day period.
b) Oral corticosteroid treatment must be stabilized for at least 25 out of 28 days prior
to treatment, (Day 1).
6) At screening, subjects must have a DAS28 = 5.1.

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:
1) Women who are pregnant or breastfeeding.
2) Women with a positive pregnancy test on enrollment or prior to start of study drug
administration.
3) WOCBP using a prohibited contraceptive method (there are none).
4) 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 study medication.
5) Males unwilling or unable to use an adequate method contraception for the entire
study period and for up to 10 weeks after the last infusion of study medication.
6) Subjects with active vasculitis of a major organ system (except for subcutaneous
rheumatoid nodules).
7) Current symptoms of severe, progressive, or uncontrolled renal, hepatic,
hematological, gastrointestinal, pulmonary, cardiac, neurological, ophthalmologic or
cerebral disease. Concomitant medical conditions that in the opinion of the
Investigator might place the subject at unacceptable risk for participation in this
study.
8) 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.
9) Subjects who have a history of clinically significant drug or alcohol abuse. Subjects
currently taking methotrexate or leflunomide who admit to consumption of more than
an average of 1 alcoholic drink per day.
10) Subjects with any serious bacterial infection (such as pneumonia, other renal infection
and sinusitis), unless treated and resolved with antibiotics or chronic bacterial
infection (such as pyelonephritis and chest infection with bronchiectasis) in the
previous 3 months.
11) Subjects with active tuberculosis requiring treatment within the previous 3 years.
Subjects with a positive PPD at screening will not be eligible for the study unless they
completed treatment for latent TB and have a negative chest x-ray at enrollment.
12) Subjects with herpes zoster that resolved less than 2 months prior to enrollment.
13) Subjects with evidence (as assessed by the Investigator) of active or latent bacterial or viral infections at the time of potential enrollment, including subjects with evidence of Human Immunodeficiency Virus (HIV) infection.
14) Significant toxicities associated with concomitant DMARD therapy or previous
anti-TNF therapy that would preclude subjects from participating and completing the
study.
15) Subjects with repeated (at least 2) serious infections (such as pneumonia, other renal infections, sinusitis) requiring intravenous therapy while on anti-TNF therapy.
16) Subjects with a history of severe allergic reaction(s) to Anti- TNF therapy.
17) 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.
• Any other laboratory test results that, in the opinion of the investigator, might
place the subject at unacceptable risk for participation in this study.
18) Subjects previously treated with rituximab: B cell levels are less than lower limit of normal as measured by Fluorescent Activated Cell Sorting (FACS) analysis.
19) Subjects who have at any time received treatment with BMS-188667, CTLA4Ig or
abatacept.
20) Subjects who have received treatment with any investigational drug within 28 days of the Day 1 dose.
21) Subjects currently receiving treatment wi


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
RHEUMATOID ARTHRITIS,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-

Primary Outcome(s)
Main Objective: The study will summarize the incidence of adverse events, serious adverse events and discontinuations due to adverse events during 6 months of combined treatment with abatacept and one or more of the background non-biologic DMARDs approved for RA in subjects with active RA.
Primary end point(s): Physical examination findings, vital signs, laboratory test results and adverse events will be evaluated during the course of the study. Clinical response will be evaluated by the Disease Activity Score (DAS28) criteria. The DAS28 measures the current RA disease activity. The variables used to calculate the DAS28 include the number of swollen and tender joints using 28-joint counts, hs-CRP (measured in mg/L), the subject global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm. Other responses (e.g.HAQ) outcome measures (e.g., SF-36), physician’s global assessment of disease activity will also be evaluated.
Secondary Objective: 1) Assess percentage of subjects achieving a clinically meaningful improvement in
DAS28 (reduction of at least 1.2 units) at Day 169 (Month 6).
2) Assess percentage of subjects achieving Low Disease Activity (DAS28 < 3.2) at
Day 169 (Month 6).
3) Assess Percentage of subjects achieving remission (DAS28 < 2.6) at Day 169
(Month 6)
4) Assess disease activity as measured by Disease Activity Score-28 (DAS28) over time
5) Assess the safety of chronic use of abatacept.
6) Assess the discontinuation rate in subjects receiving abatacept.
7) Assess the immunogenicity of abatacept.
8) Assess changes in surrogate markers (hs-CRP, RF) in subjects receiving abatacept.
9) Assess improvement in physical functioning (HAQ) at Day 169 (Month 6)
10) Assess improvement in SF36 at Day 169 (Month 6)
11) Assess reduction in fatigue using Fatigue VAS at Day 169 (Month 6)
12) Assess the incidence of adverse events, serious adverse events and discontinuations between current and previous users.
Secondary Outcome(s)
Secondary ID(s)
2004-005102-68-GB
IM101-064
Source(s) of Monetary Support
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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