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

NCT00767325 | Completed Phase 3 Results

• 1 other identifier: IM101-179
• Study Type: interventional
• Target: 104
• Locations: 8 countries
• Sites: 21

Brief 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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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.

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

Secondary Outcomes (4)

• Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis)

  Days 7, 15, 29, and 169

• 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

  Days 1 to 169

• 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

  Days 1 to 169 to 56 days following last infusion

• Number of Participants With Adverse Events (AEs) of Interest

  Days 1 to 169 to 56 days following last infusion

Study Arms (1)

Abatacept, 10 mg/kg

EXPERIMENTAL

Drug: Abatacept; Drug: Methotrexate

Interventions

Abatacept DRUG

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

Also known as: Orencia®, BMS-188667

Abatacept, 10 mg/kg

Methotrexate DRUG

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

Abatacept, 10 mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (21)

Local Institution

Glostrup Municipality, DK-2600, Denmark

Location

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Bois-Guillaume, 76230, France

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Boulogne, 92104, France

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Échirolles, 38434, France

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Nice, 06202, France

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München, 80639, Germany

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Budapest, 1036, Hungary

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Jesi (Ancona), 60035, Italy

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Pisa, 56126, Italy

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Roma, 00161, Italy

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Roma, 00168, Italy

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Siena, 53100, Italy

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Verona, 37126, Italy

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Oslo, N0319, Norway

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Trondheim, 7006, Norway

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Barcelona, 08006, Spain

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Madrid, 28006, Spain

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Madrid, 28040, Spain

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Madrid, 28911, Spain

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Local Institution

Madrid, 28935, Spain

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Local Institution

Leeds, North Yorkshire, LS7 4SA, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 27175297 DERIVED

• 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.

  PMID: 26714738 DERIVED

• 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.

  PMID: 26590174 DERIVED

Related Links

• Investigator Inquiry form

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Abatacept; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Power Doppler ultrasonography values from 1 site (8 participants were excluded due to technical and quality issues with PDUS scoring and compliance issues.)

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2008
• First Posted: October 7, 2008
• Study Start: December 1, 2008
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: July 2, 2013
• Results First Posted: June 21, 2013

Record last verified: 2013-06

Locations

FR (4); GB (1); DK (1); ES (5); IT (6); NO (2); DE (1); HU (1)