Clinical trial NCT00767325: A Rheumatoid Arthritis Study to Assess Early Response to Abatacept+MTX as Defined by Improvement of Synovitis Measures by Power Doppler Ultrasonography
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2008-10-07
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.


Eligibility criteria: Key inclusion riteria:

* 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

Key exclusion criteria:

* 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
* 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

Primary outcomes:
measure: Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis)
timeFrame: Baseline to Days 7, 15, 29, 43, 57, 85, 113, 141, and 169
measure: Earliest Time Point at Which Improvement of Core Component of the Global PDUS in the MCP (2-5) Joints of Both Hands Was Assessed
timeFrame: Baseline to Days 7, 15, 29, 43, 57, 85, 113, 141, and 169
Secondary outcomes:
measure: Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis)
timeFrame: Days 7, 15, 29, and 169
measure: 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
timeFrame: Days 1 to 169
measure: 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
timeFrame: Days 1 to 169 to 56 days following last infusion
measure: Number of Participants With Adverse Events (AEs) of Interest
timeFrame: Days 1 to 169 to 56 days following last infusion
Other outcomes:
Locations:
city: Glostrup
country: Denmark
facility: Local Institution
city: Bois Guillaume Cedex
country: France
facility: Local Institution
city: Boulogne
country: France
facility: Local Institution
city: Echirolles
country: France
facility: Local Institution
city: Nice Cedex 03
country: France
facility: Local Institution
city: Munchen
country: Germany
facility: Local Institution
city: Budapest
country: Hungary
facility: Local Institution
city: Jesi (Ancona)
country: Italy
facility: Local Institution
city: Pisa
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution
city: Siena
country: Italy
facility: Local Institution
city: Verona
country: Italy
facility: Local Institution
city: Oslo
country: Norway
facility: Local Institution
city: Trondheim
country: Norway
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Leeds
country: United Kingdom
facility: Local Institution
state: North Yorkshire
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.