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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: 19 March 2012
Main ID:  EUCTR2006-003768-67-NL
Date of registration: 27/03/2007
Prospective Registration: Yes
Primary sponsor: Bristol-Myers Squibb International Corporation
Public title: A Phase III Multicenter, Randomized, Double-Blind, placebo-controlled Study to Assess short-term changes in synovitis and structural damage outcomes in subjects with active Rheumatoid Arthritis and inadequate response to Methotrexate, Treated with Abatacept versus Placebo on a Background Therapy with Methotrexate
Scientific title: A Phase III Multicenter, Randomized, Double-Blind, placebo-controlled Study to Assess short-term changes in synovitis and structural damage outcomes in subjects with active Rheumatoid Arthritis and inadequate response to Methotrexate, Treated with Abatacept versus Placebo on a Background Therapy with Methotrexate
Date of first enrolment: 16/05/2007
Target sample size: 58
Recruitment status: Not Recruiting
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-003768-67
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: The double-blind phase is followed by an open-label phase of 8 months. If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no  
Phase: 
Countries of recruitment
Austria Germany Netherlands Spain Sweden United Kingdom
Contacts
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Key inclusion & exclusion criteria
Inclusion criteria:
1) Signed written informed consent
2) Subjects must meet the criteria of the American Rheumatism Association (1987)
for the diagnosis of rheumatoid arthritis (Protocol Appendix 1).
3) Subjects must have a diagnosis of RA greater than 6 months and no longer than 5
years from the time of initial diagnosis of RA.
4) Subjects must have a disease activity as defined by a tender joint count of >= 6,
swollen joint count of >= 6, and a CRP of at least 1.5 times the upper limit of normal
5) Subjects must have clinically detectable synovitis (i.e. “synovial swelling”) of at
least one wrist at screening and baseline visit (D1, prior to infusion).
6) Subjects must have at least one erosion present in the hands/wrists and /or feet
(documented by previous plain radiography) or be anti-CCP positive or have a
rheumatoid factor (RF) titer >1:160.
7) Subjects must have been treated with MTX, on a stable dose of at least 15 mg or a maximum tolerated dose (i.e. 10 mg weekly) for at least 3 months before screening
8) Subjects must be biologic DMARDs naive (i.e. anti-TNFa, anakinra, rituximab or
other investigational biologics).
9) Subjects who consented to have a knee/ankle arthroscopy with tissue and synovial biopsy must have clinically detectable synovitis (i.e. “synovial swelling”) of at
least one knee/ankle at screening and baseline visit (D1).
10) At randomization (Day 1), subjects must have the following disease activity :
a) 6 or more swollen joints (66 joint count) and
b) 6 or more tender joints (68 joint count) and
c) CRP of at least 1.5 times the upper limit of normal at screening and baseline
visit (D1, prior to infusion). (result used from screening visit sample collection).
11) Drug stabilization requirements (except MTX): Informed consent must be
signed before making any changes in RA therapy if those changes are solely for
the purpose of this study.
a) All DMARDs (except MTX) should be discontinued at least 28 days prior to
treatment (Day 1).
-MTX monotherapy: Subjects who are treated only with MTX will not
require washout.
-Combination DMARD therapy: Subjects who are treated with MTX in
combination with another anti-rheumatic treatment (DMARD) will
require washout.
b) In the case of leflunomide, the subject can be washed-out with cholestyramine
according to manufacturer recommendations.
c) 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 (Baseline i.e. Day 1).
12) Osteoporosis treatment:
Subjects taking treatments for the prevention of glucocorticoid-induced osteoporosis
(Calcium, vitamin D, Bisphosphonates) will be enrolled as long as their dose has been
stable for at least 3 months prior to randomization and remains stable during the entire double-blind period. Other concomitant osteoporosis treatments will not be permitted at randomization.
13) Men and women (not nursing and not pregnant) >= 18 years of age. Women of
childbearing potential are eligible if they are practicing effective contraceptive
measures.

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)WOCBP unwilling or unable to use acceptable method to avoid pregnancy for entire study period & up to 10 weeks after study
2)WOCBP using prohibited contraceptive method
3)Pregnant or breastfeeding women
4)Women with + pregnancy test on enrollment or prior to study drug administration
5)Contraception for male subjects treated with protocol-permitted concomitant
medications during study should follow manufacturer’s recommendation for need to use contraception & permissible/recommended method(s)
6)Subjects who are impaired, incapacitated, or incapable of completing study
related assessments
7)Subjects meeting diagnostic criteria for any other rheumatic disease (e.g. lupus
erythematous)
8)previous treatment with approved/investigational biologic RA therapy (infliximab, etanercept,anakinra,adalimumab,rituximab,Abatacept)
9)Active vasculitis of a major organ system with exception of
rheumatoid nodules
10)current symptoms of severe,progressive, or uncontrolled renal, hepatic,hematological,gastrointestinal,pulmonary,cardiac,neurological, or
cerebral disease, or other medical conditions that, in opinion of the investigator, might place subject at unacceptable risk for participation
11)Female subjects who have had breast cancer screening suspicious for
malignancy & in whom possibility of malignancy cannot be reasonably excluded following additional clinical,laboratory or other diagnostic evaluations
(Protocol Section 7.3.2.3)
12)history of cancer within last 5 years (other than nonmelanoma skin cell (NMSC) cancers cured by local resection). Existing NMSC cancers must be removed prior to dosing
13)Known current metabolic bone disorders other than osteoporosis or low bone mass (hyperparathyroidism, renal osteodystrophy, osteomalacia)
14)Vitamin D deficiency
15)Clinically significant drug or alcohol abuse
16)Subjects with any serious bacterial infection within last 3 months, unless treated & resolved with antibiotics, or any chronic bacterial infection (chronic pyelonephritis, osteomyelitis & bronchiectasis)
17)Subjects at risk for TB. Specifically subjects with:
-History of active TB within last 3 years even if treated
-History of active TB >3 years ago unless there is documentation
that prior anti-TB treatment was appropriate in duration & type
-Current clinical, radiographic or laboratory evidence of active TB
-Latent TB which was not successfully treated
18)Subjects with herpes zoster or CMV that resolved less than 2 months prior to signing ICF
19)Subjects with evidence of active or latent bacterial/viral infections at time of potential enrollment, including subjects with evidence of HIV, HPB or HPC infection detected during screening
20)Subjects with conditions that preclude accurate DXA measurements
including:
-BMI >35 kg/m²
- Advanced scoliosis or spinal degenerative changes (osteoarthritis, sclerosis)
-Less than 3 lumbar vertebrae in range L1-L4 which are evaluable by DXA
interfering conditions include prevalent vertebral fracture, metal implants or spinal
surgery
-History of bilateral distal radius fracture
21)Subject who received live vaccines within 3 months of anticipated
1st dose of study medication or who will have need of live vaccine at any time
following Day 1 of study
22)History of severe or anaphylactic infusion reaction after receiving a biologic
agent, suspected to be associated with an immune response
23)Subjects who have at any time received treatment with Abatacept
24)Subjects who have at any time received treatme


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
RHEUMATOID ARTHRITIS,NOS
MedDRA version: 8.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis
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

Primary Outcome(s)
Main Objective: The primary objective of this study in subjects with active RA and inadequate response to MTX is to assess changes in wrist synovitis as measured by gadolinium-enhanced Magnetic Resonance Imaging (MRI) and using the OMERACT 6 RA MRI score after 4 months of treatment with Abatacept or placebo, on a background therapy with MTX.
Primary end point(s): Imaging assessments:

• MRI assessment of the degree of inflammation and structural damage [i.e. synovitis of the most clinically inflamed wrists and bone edema and erosions of the target wrist and metacarpophalangeal (MCP) joints] at baseline (D1), 4 months (end of double-blind treatment period) and 1 year (end of open-label extension) by gadolinium-enhanced MRI, using a centralized reader blinded to sequence and treatment and using the OMERACT 6 RA MRI score.

Secondary Objective: 1) To assess in subjects with active RA and inadequate response to MTX changes in
bone lesions (i.e. bone edema, bone erosions) in hands/wrists (measured by
gadolinium-enhanced MRI, using the OMERACT 6 RA MRI score) after 4 months of treatment with Abatacept or placebo, on a background therapy with MTX).
2) To assess in subjects with active RA and inadequate response to MTX changes in
biochemical markers of bone, cartilage and synovial tissue metabolism at Days 15, 29 and 113 (4 months) after 4 months of treatment with Abatacept or placebo, on a background therapy with MTX.
3) To assess the safety and tolerability of Abatacept versus placebo in subjects with
active RA and inadequate response to MTX, on a background therapy with MTX over 4 months.
Secondary Outcome(s)
Secondary ID(s)
2006-003768-67-SE
IM101119
Source(s) of Monetary Support
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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