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Rheumatoid ArthritisPhase 3NCT00767325

A Rheumatoid Arthritis Study to Assess Early Response to Abatacept+MTX as Defined by Improvement of Synovitis Measures by Power Doppler Ultrasonography

A Phase 3 study testing Abatacept and Methotrexate in people with Rheumatoid Arthritis, run by Bristol-Myers Squibb at 21 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of the study is to assess early signs of response to abatacept+methotrexate in metacarpophalangeal joints in both hands using power Doppler ultrasonography in patients with active rheumatoid arthritis. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Rheumatoid Arthritis
What is being tested?
Abatacept and Methotrexate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
104 participants
Where
21 sitesin 8 countries
Study dates
Dec 2008to Oct 2011
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Disease activity defined by a disease activity score 28-C-reactive protein >3.2, or meeting the following criteria: a tender joint count ≥6; a swollen joint count ≥6; C-reactive protein measurement greater than the upper limit of normal
  • Diagnosis of rheumatoid arthritis for longer than 6 months from time of initial diagnosis
  • Total synovitis power Doppler ultrasonography (PDUS) score >1 for at least 2 metacarpophalangeal (MCP) joints (MCP2-5) and a total synovitis PDUS score ≥1 for at least 1 other MCP joint (MCP2-5)
  • Concomitant treatment with methotrexate at a dose ≥15 mg for at least 3 months before Day 1 and a stable dose for the last 28 days before Day 1
  • No treatment with any background nonbiologic disease-modifying antirheumatic drug (DMARD) other than methotrexate for at least 28 days before treatment (Day 1)
  • Stable dose of corticosteroids equivalent of 10 mg prednisone /day during the 28 days prior to Day 1
  • Naive to treatment with biologic DMARDs

Who cannot join

  • Women of childbearing potential who are unwilling or unable to use birth control
  • Women who are pregnant or breastfeeding
  • Meeting all diagnostic criteria for any other rheumatic disease
  • Previous MCP arthroplasty, with such a procedure scheduled, or anticipating the need for such a procedure during the study. Participants who had undergone or were scheduled to undergo joint arthroplasties other than of the MCP joints were permitted to enroll in the study provided all other eligibility criteria were met.
  • Active vasculitis of a major organ system with the exception of rheumatoid nodule
  • Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, pulmonary, cardiac, neurologic, or cerebral disease, whether or not related to rheumatoid arthritis
Show all 17Show fewer
  • History of cancer in the last 5 years, other than nonmelanoma skin cell cancer cured by local resection or carcinoma in situ. Existing nonmelanoma skin cell cancers should have been removed, the lesion site healed, and residual cancer ruled out prior to administration of study medication
  • Clinically significant abuse of alcohol or drugs
  • Evidence of active or latent bacterial or viral infections at the time of potential enrollment
  • Herpes zoster or cytomegalovirus infection that resolved less than 2 months before the informed consent document was signed
  • For participants at risk for tuberculosis (TB):
  • A history of active (TB) within the last 3 years, even if treated
  • Latent TB that was not successfully treated ≥4 weeks
  • Current clinical, radiographic, or laboratory evidence of active TB.
  • Participants who have received live vaccines within 3 months of the anticipated first dose of study medication
  • Participants with positive test results for hepatitis B surface antigen or hepatitis C antibody, with hepatitis C virus detected with polymerase chain reaction or recombinant immunoblot assay.
  • Participants with hemoglobin level <8.5 g/dL or white blood cell count< 3000/mm^3 or platelet count <100,000/mm^3 or serum creatinin level >2*the upper limit of normal (ULN) or serum alanine transaminase level or aspartate aminotransferase level >2*ULN

Trial locations and contacts

21 sites in 8 countries.

21 sites in 8 countries

Italy6 sites
  • Local Institution

    Jesi (Ancona), 60035

  • Local Institution

    Pisa, 56126

  • Local Institution

    Roma, 00161

  • Local Institution

    Roma, 00168

  • Local Institution

    Siena, 53100

  • Local Institution

    Verona, 37126

Other trials in Italy

Spain5 sites
  • Local Institution

    Barcelona, 08006

  • Local Institution

    Madrid, 28006

  • Local Institution

    Madrid, 28040

  • Local Institution

    Madrid, 28911

  • Local Institution

    Madrid, 28935

Other trials in Spain

France4 sites
  • Local Institution

    Bois-Guillaume, 76230

  • Local Institution

    Boulogne, 92104

  • Local Institution

    Échirolles, 38434

  • Local Institution

    Nice, 06202

Other trials in France

Norway2 sites
  • Local Institution

    Oslo, N0319

  • Local Institution

    Trondheim, 7006

Other trials in Norway

Denmark1 site
  • Local Institution

    Glostrup Municipality, DK-2600

Other trials in Denmark

Germany1 site
  • Local Institution

    München, 80639

Other trials in Germany

Hungary1 site
  • Local Institution

    Budapest, 1036

Other trials in Hungary

United Kingdom1 site
  • Local Institution

    Leeds, North Yorkshire, LS7 4SA

Other trials in United Kingdom

About this study

Official title: Multi-Center, Open Label Study to Assess Early Response to Abatacept With Background Methotrexate Using Power Doppler Ultrasonography in Patients With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate

The purpose of the study is to assess early signs of response to abatacept+methotrexate in metacarpophalangeal joints in both hands using power Doppler ultrasonography in patients with active rheumatoid arthritis.

Being tested
Abatacept, Methotrexate
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AbataceptDrug

    Also called Orencia®, BMS-188667

    Abatacept, 10 mg/kg, solution given intravenously on Days 1, 15, 29,57, 85, 113, 141, and 169

  • MethotrexateDrug

    Methotrexate administered in a dose of 15 mg/week or higher for at least 3 months and at a stable dose for at least 28 days prior to baseline

Study groups in NCT00767325
Study groupRoleWhat they receive
Abatacept, 10 mg/kgExperimentalNot described
Receives: Drug: Abatacept; Drug: Methotrexate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis)

    LOCF=last observation carried forward. PDUS assessed the degree of synovial inflammation of the MCP joints (2nd to 5th) of both hands and was performed at approximately the same time of day for each participant. Total PDUS scores are independent of the presence and grade of joint effusion and are evaluated as follows: Grade 0 or normal=normal joint (no synovial hypertrophy, no Doppler signal); Grade 1 or minimal=minimal synovitis (minimal synovial hypertrophy, with ≤Grade 1 Doppler signal); Grade 2 or moderate=moderate synovitis (moderate synovial hypertrophy with ≤Grade 2 Doppler signal or minimal synovial hypertrophy and Grade 2 Doppler signal; Grade 3 or severe=severe synovitis (severe synovial hypertrophy with ≤Grade 3 Doppler signal or minimal or moderate synovial hypertrophy and Grade 3 Doppler signal). Each joint is rated 1 to 3, for a total possible score ranging from 8 to 24 (8*1, 8*3) for 2 hands. Higher grade/score=more severe disease. Change=score Day x - baseline score.

    Measured: Baseline to Days 7, 15, 29, 43, 57, 85, 113, 141, and 169

  2. Earliest Time Point at Which Improvement of Core Component of the Global PDUS in the MCP (2-5) Joints of Both Hands Was Assessed

    MCP=metacarpophalangeal; PDUS=power Doppler ultrasonography. Time point at which early signs of Global PDUS improvement were observed=earliest time point for which 0 was not included in the 95% confidence interval for the mean changes from baseline in Global PDUS (MCP 2-5) score at that and all later time points. Total PDUS scores are independent of the presence and grade of joint effusion: Grade (Gr) 0 or normal=normal joint (no synovial hypertrophy [SH], no Doppler signal); Gr 1 or minimal=minimal synovitis (minimal SH, with ≤Gr 1 Doppler signal); Gr 2 or moderate=moderate synovitis (moderate SH, with ≤Gr 2 Doppler signal or minimal SH and grade 2 Doppler signal); Gr 3 or severe=severe synovitis (severe SH with ≤Gr 3 Doppler signal or minimal or moderate SH and Gr 3 Doppler signal). Each joint is rated 1 to 3, for a total possible score ranging from 8 to 24 (8*1, 8*3) for the 2 hands. Higher Gr/score=more severe disease.

    Measured: Baseline to Days 7, 15, 29, 43, 57, 85, 113, 141, and 169

Secondary outcomes (4)
  1. Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis)

    PDUS=power Doppler ultrasonography; MCP=metacarpophalangeal; LOCF=last observation carried forward. PDUS was used to assess the degree of synovial inflammation of the MCP joints (2nd to 5th) of both hands and was performed at approximately the same time of day for each participant. PDUS scores are independent of the presence and grade of joint effusion and are evaluated as follows: Grade 0 or normal=normal joint (no synovial hypertrophy, no Doppler signal); Grade 1 or minimal=minimal synovitis (minimal synovial hypertrophy, with ≤Grade 1 Doppler signal); Grade 2 or moderate=moderate synovitis (moderate synovial hypertrophy with ≤Grade 2 Doppler signal or minimal synovial hypertrophy and grade 2 Doppler signal); Grade 3 or severe=severe synovitis (severe synovial hypertrophy with ≤ Grade 3 Doppler signal or minimal or 1-3, for a total possible score ranging from 8 to 24 (8*1, 8*3) for the 2 hands. Higher grade/score=more severe disease. Change=score Day X-baseline score.

    Measured: Days 7, 15, 29, and 169

  2. Number of Early (Days 7 to 113) Global PDUS MCP 2-5 Scores or Global PDUS Component MCP 2-5 Scores Associated With an Acceptable Predictability of Clinical Response at Day 169, As Assessed by DAS28-CRP

    MCP=metacarpophalangeal; PDUS=power Doppler ultrasonography; DAS=Disease Activity Score;CRP=C-reactive protein. Receiver Operator Characteristics (ROC) analysis assessed predicatability. ROC curve analyses performed; area under the curve of ≥0.7 was considered acceptable for prediction. Clinical response defined as: Clinically Meaningful Improvement=drop from baseline of ≥1.2 in DAS28-CRP; Remission=DAS28-CRP score <2.6; Low Disease Activity=≤3.2. PDUS scores: Grade (Gr) 0 or normal=normal joint (no synovial hypertrophy [SH], no Doppler signal); Gr 1 or minimal=minimal synovitis (minimal SH, with ≤Gr 1 Doppler signal); Gr 2 or moderate=moderate synovitis (moderate SH with ≤Gr 2 Doppler signal or minimal SH and Gr 2 Doppler signal); Gr 3 or severe=severe synovitis (severe SH with ≤Gr 3 Doppler signal or minimal or moderate SH and Gr 3 Doppler signal). Each joint rated 1-3, for a total possible score ranging from 8-24 (8*1, 8*3)for the 2 hands. Higher gr/score=more severe disease.

    Measured: Days 1 to 169

  3. Number of Participants With Death as Outcome, Serious Adverse Events(SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, Discontinuations Due to AEs

    AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug.

    Measured: Days 1 to 169 to 56 days following last infusion

  4. Number of Participants With Adverse Events (AEs) of Interest

    AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Infusion reaction: acute=1 hour or less after start of dosing; periinfusional=24 hours or less after start of dosing.

    Measured: Days 1 to 169 to 56 days following last infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Oct 2008 (estimated)
  2. Study startDec 2008
  3. Primary completionOct 2011
  4. Study completionOct 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
104 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00767325
Sponsor's protocol ID
IM101-179
Status last verified
Jun 2013
First submitted
6 Oct 2008
Last updated
2 Jul 2013
Data monitoring committee
No

Publications

  • D'Agostino MA, Boers M, Wakefield RJ, Berner Hammer H, Vittecoq O, Filippou G, Balint P, Moller I, Iagnocco A, Naredo E, Ostergaard M, Gaillez C, Le Bars M. Exploring a new ultrasound score as a clinical predictive tool in patients with rheumatoid arthritis starting abatacept: results from the APPRAISE study. RMD Open. 2016 May 5;2(1):e000237. doi: 10.1136/rmdopen-2015-000237. eCollection 2016.

    PubMed 27175297
  • Golinski ML, Vandhuick T, Derambure C, Freret M, Lecuyer M, Guillou C, Hiron M, Boyer O, Le Loet X, Vittecoq O, Lequerre T. Dysregulation of RasGRP1 in rheumatoid arthritis and modulation of RasGRP3 as a biomarker of TNFalpha inhibitors. Arthritis Res Ther. 2015 Dec 26;17:382. doi: 10.1186/s13075-015-0894-9.

    PubMed 26714738
  • D'Agostino MA, Wakefield RJ, Berner-Hammer H, Vittecoq O, Filippou G, Balint P, Moller I, Iagnocco A, Naredo E, Ostergaard M, Boers M, Gaillez C, Van Holder K, Le Bars M; OMERACT-EULAR-Ultrasound Task Force. Value of ultrasonography as a marker of early response to abatacept in patients with rheumatoid arthritis and an inadequate response to methotrexate: results from the APPRAISE study. Ann Rheum Dis. 2016 Oct;75(10):1763-9. doi: 10.1136/annrheumdis-2015-207709. Epub 2015 Nov 20.

    PubMed 26590174

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Abatacept and Methotrexate in people with Rheumatoid Arthritis, run by Bristol-Myers Squibb at 21 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in Italy, Spain, France, Norway, Denmark and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Jun 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis) (time frame: Baseline to Days 7, 15, 29, 43, 57, 85, 113, 141, and 169). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00767325, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2013.

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