Phase IIB Rheumatoid Arthritis Dose Ranging Study for BMS-945429 in Subjects Who Are Not Responding to Methotrexate

A Phase IIB , Randomized, Multi-Center, Double-Blind, Dose-Ranging, Placebo/Active Controlled Study to Evaluate the Efficacy and Safety of BMS-945429 Subcutaneous Injection With or Without Methotrexate in Subjects With Moderate to Severe Rheumatoid Arthritis With Inadequate Response to Methotrexate.

The purpose of this study is to determine the effective dose of BMS-945429 in subjects with inadequate response to Methotrexate in the treatment of moderate to severe Rheumatoid Arthritis.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: BMS-945429 Placebo; Biological: BMS-945429; Biological: BMS-945429; Biological: BMS-945429; Biological: BMS-945429; Drug: Methotrexate; Drug: Methotrexate; Drug: Methotrexate; Drug: Adalimumab Placebo; Drug: Methotrexate Placebo; Drug: Adalimumab

• Study Type: Interventional
• Enrollment (Actual): 418
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Cordoba, Argentina, 5000
    • Local Institution
  • San Juan, Argentina, 5400
    • Local Institution
  • Buenos Aires
    • Capital Federal, Buenos Aires, Argentina, 1431
      • Local Institution
    • Capital Federal, Buenos Aires, Argentina, 1425
      • Local Institution
    • Capital Federal, Buenos Aires, Argentina, 1015
      • Local Institution
    • Capital Federal, Buenos Aires, Argentina, 1428
      • Local Institution
  • Santa FE
    • Rosario, Santa FE, Argentina, 2000
      • Local Institution
  • Tucuman
    • San Miguel De Tucuman, Tucuman, Argentina, 4000
      • Local Institution
• Belgium
  • Bruxelles, Belgium, 1200
    • Local Institution
  • Hasselt, Belgium, 3500
    • Local Institution
• Brazil
  • Sao Paulo, Brazil, 04032
    • Local Institution
  • Sao Paulo, Brazil, 04266
    • Local Institution
  • Goias
    • Goiania, Goias, Brazil, 74110
      • Local Institution
  • Minas Gerais
    • Juiz De Fora, Minas Gerais, Brazil, 36010
      • Local Institution
  • Parana
    • Curitiba, Parana, Brazil, 80060
      • Local Institution
    • Curitiba, Parana, Brazil, 80440
      • Local Institution
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 91610
      • Local Institution
• Canada
  • Quebec, Canada, G1W 4R4
    • Local Institution
  • Quebec
    • Montreal, Quebec, Canada, H2L 1S6
      • Local Institution
    • Trois-rivieres, Quebec, Canada, G8Z 1Y2
      • Centre de Recherche Musculo-Squelettique
• Czechia
  • Praha 2, Czechia, 128 50
    • Local Institution
  • Praha 4, Czechia, 140 59
    • Local Institution
• France
  • Bordeaux Cedex, France, 33076
    • Local Institution
  • Chambray Les Tours, France, 37170
    • Local Institution
  • Strasbourg Cedex, France, 67098
    • Local Institution
• Germany
  • Berlin, Germany, 14059
    • Local Institution
  • Koeln, Germany, 50931
    • Local Institution
  • Leipzig, Germany, 04103
    • Local Institution
  • Wuerzburg, Germany, 97080
    • Local Institution
• Hungary
  • Budapest, Hungary, 1027
    • Local Institution
  • Debrecen, Hungary, 4012
    • Local Institution
  • Gyula, Hungary, 5700
    • Local Institution
  • Veszprem, Hungary, 8200
    • Local Institution
• Italy
  • Napoli, Italy, 80131
    • Local Institution
  • Padova, Italy, 35128
    • Local Institution
  • Reggio Emilia, Italy, 42100
    • Local Institution
• Japan
  • Chiba
    • Chiba-shi, Chiba, Japan, 2608712
      • Local Institution
  • Fukuoka
    • Kitakyushu-shi, Fukuoka, Japan, 8078555
      • Local Institution
  • Hiroshima
    • Higashi-hiroshima-shi, Hiroshima, Japan, 7390002
      • Local Institution
  • Hyogo
    • Kato-shi, Hyogo, Japan, 6731462
      • Local Institution
  • Miyazaki
    • Miyazaki-shi, Miyazaki, Japan, 8800122
      • Local Institution
  • Nagano
    • Nagano-shi, Nagano, Japan, 3808582
      • Local Institution
  • Nagasaki
    • Nagasaki-shi, Nagasaki, Japan, 8528501
      • Local Institution
    • Sasebo-shi, Nagasaki, Japan, 8571195
      • Local Institution
  • Okinawa
    • Tomigusuku-shi, Okinawa, Japan, 9010243
      • Local Institution
  • Osaka
    • Osaka-shi, Osaka, Japan, 5458586
      • Local Institution
  • Shizuoka
    • Shizuoka-shi, Shizuoka, Japan, 4208623
      • Local Institution
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 1138519
      • Local Institution
    • Shinjuku-Ku, Tokyo, Japan, 1608582
      • Local Institution
    • Toshima-ku, Tokyo, Japan, 1708476
      • Local Institution
• Korea, Republic of
  • Daegu, Korea, Republic of, 705-718
    • Local Institution
  • Seoul, Korea, Republic of, 137-701
    • Local Institution
  • Seoul, Korea, Republic of, 133-792
    • Local Institution
• Mexico
  • San Luis Potosi, Mexico, 78213
    • Local Institution
  • Distrito Federal
    • Mexico City, Distrito Federal, Mexico, 11850
      • Local Institution
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 42650
      • Local Institution
    • Guadalajara, Jalisco, Mexico, 45040
      • Local Institution
  • Michioacan
    • Morelia, Michioacan, Mexico, 58270
      • Local Institution
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64020
      • Local Institution
  • Sinaloa
    • Culiacan, Sinaloa, Mexico, 80230
      • Local Institution
• Netherlands
  • Amsterdam, Netherlands, 1056 AB
    • Local Institution
• Poland
  • Katowice, Poland, 40-748
    • Local Institution
  • Krakow, Poland, 31-531
    • Local Institution
  • Poznan, Poland, 60773
    • Local Institution
  • Warszawa, Poland, 01-868
    • Local Institution
  • Warszawa, Poland, 02-118
    • Local Institution
• Russian Federation
  • Ekaterinburg, Russian Federation, 620102
    • Local Institution
  • Kazan, Russian Federation, 420064
    • Local Institution
  • Moscow, Russian Federation, 115522
    • Local Institution
  • Novosibirsk, Russian Federation, 630005
    • Local Institution
  • St. Petersburg, Russian Federation, 191014
    • Local Institution
  • Yaroslavl, Russian Federation, 150003
    • Local Institution
• South Africa
  • Gauteng
    • Pretoria, Gauteng, South Africa, 0083
      • Local Institution
    • Pretoria, Gauteng, South Africa, 0132
      • Local Institution
  • KWA ZULU Natal
    • Durban, KWA ZULU Natal, South Africa, 4001
      • Local Institution
  • Western CAPE
    • Panorama, Western CAPE, South Africa, 7500
      • Local Institution
    • Tygerberg, Western CAPE, South Africa, 7505
      • Local Institution
  • Western Cape
    • Pinelands, Cape Town, Western Cape, South Africa, 7405
      • Local Institution
• Spain
  • A Coruna, Spain, 15006
    • Local Institution
  • Madrid, Spain, 28040
    • Local Institution
  • Santander, Spain, 39008
    • Local Institution
  • Santiago De Compostela, Spain, 15706
    • Local Institution
  • Sevilla, Spain, 41071
    • Local Institution
• Taiwan
  • Changhua, Taiwan, 500
    • Local Institution
  • Kaohsiung, Taiwan, 833
    • Local Institution
  • Taichung, Taiwan, 404
    • Local Institution
  • Taoyuan, Taiwan, 333
    • Local Institution
• United States
  • Arizona
    • Peoria, Arizona, United States, 85381
      • Sun Valley Arthritis Center, Ltd.
  • California
    • San Diego, California, United States, 92108
      • San Diego Arthritis Medical Clinic
  • Connecticut
    • Trumbull, Connecticut, United States, 06611
      • New England Research Associates, LLC
  • Illinois
    • Quincy, Illinois, United States, 62301
      • Quincy Medical Group
    • Rockford, Illinois, United States, 61107
      • Rockford Orthopedic Associates, Llc.
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • Clinical Pharmacology Study Group
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • Arthritis Associates Of Mississippi
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Physician Research Collaboration, LLC
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Box Arthritis And Rheumatology Of The Carolinas, Pllc
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Health Research of Oklahoma
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • East Penn Rheumatology Associates, P.C.
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center For Clinical Research
  • Washington
    • Seattle, Washington, United States, 98104
      • Seattle Rheumatology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Inadequate response to Methotrexate
• Must have been taking Methotrexate for at least 3 months at a minimal weekly dose of at least 15 mg and stable dose for 4 weeks prior to randomization
• American College of Rheumatology (ACR) global function status class 1-3
• Minimum of 6 swollen and 6 tender joints with evidence of synovitis in at least 1 hand or wrist
• High sensitivity C-reactive protein (hsCRP) ≥ 0.8 mg/dL

Exclusion Criteria:

• Previously received or currently receiving concomitant biologic therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Arm 1; BMS-945429 Placebo/BMS-945429+Methotrexate+Adalimumab Placebo	Drug: BMS-945429 Placebo; Injection, Subcutaneous, 0 mg, Every 4 weeks, Day 1 - Week 24 only; Biological: BMS-945429; Injection, Subcutaneous, 25 mg, Every 4 weeks, Day 1 - Week 24 only; Biological: BMS-945429; Injection, Subcutaneous, 100 mg, Every 4 weeks, 48 weeks; Biological: BMS-945429; Injection, Subcutaneous, 200 mg, Every 4 weeks, Week 25 - Week 48; Biological: BMS-945429; Injection, Subcutaneous, 200 mg, Every 4 weeks, 48 weeks; Drug: Methotrexate; Tablets, Oral, 15 mg, Weekly, Day 1 - Week 24 only; Drug: Methotrexate; Tablets, Oral, 15 mg, Weekly, 48 weeks; Drug: Methotrexate; Tablets, Oral, 15 mg, Weekly, Week 25 - Week 48 only; Drug: Adalimumab Placebo; Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks
Experimental: Arm 2; BMS-945429 + Methotrexate + Adalimumab Placebo	Biological: BMS-945429; Injection, Subcutaneous, 25 mg, Every 4 weeks, Day 1 - Week 24 only; Biological: BMS-945429; Injection, Subcutaneous, 100 mg, Every 4 weeks, 48 weeks; Biological: BMS-945429; Injection, Subcutaneous, 200 mg, Every 4 weeks, Week 25 - Week 48; Biological: BMS-945429; Injection, Subcutaneous, 200 mg, Every 4 weeks, 48 weeks; Drug: Methotrexate; Tablets, Oral, 15 mg, Weekly, Day 1 - Week 24 only; Drug: Methotrexate; Tablets, Oral, 15 mg, Weekly, 48 weeks; Drug: Methotrexate; Tablets, Oral, 15 mg, Weekly, Week 25 - Week 48 only; Drug: Adalimumab Placebo; Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks
Experimental: Arm 3; BMS-945429 + Methotrexate + Adalimumab Placebo	Biological: BMS-945429; Injection, Subcutaneous, 25 mg, Every 4 weeks, Day 1 - Week 24 only; Biological: BMS-945429; Injection, Subcutaneous, 100 mg, Every 4 weeks, 48 weeks; Biological: BMS-945429; Injection, Subcutaneous, 200 mg, Every 4 weeks, Week 25 - Week 48; Biological: BMS-945429; Injection, Subcutaneous, 200 mg, Every 4 weeks, 48 weeks; Drug: Methotrexate; Tablets, Oral, 15 mg, Weekly, Day 1 - Week 24 only; Drug: Methotrexate; Tablets, Oral, 15 mg, Weekly, 48 weeks; Drug: Methotrexate; Tablets, Oral, 15 mg, Weekly, Week 25 - Week 48 only; Drug: Adalimumab Placebo; Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks
Experimental: Arm 4; BMS-945429 + Methotrexate + Adalimumab Placebo	Biological: BMS-945429; Injection, Subcutaneous, 25 mg, Every 4 weeks, Day 1 - Week 24 only; Biological: BMS-945429; Injection, Subcutaneous, 100 mg, Every 4 weeks, 48 weeks; Biological: BMS-945429; Injection, Subcutaneous, 200 mg, Every 4 weeks, Week 25 - Week 48; Biological: BMS-945429; Injection, Subcutaneous, 200 mg, Every 4 weeks, 48 weeks; Drug: Methotrexate; Tablets, Oral, 15 mg, Weekly, Day 1 - Week 24 only; Drug: Methotrexate; Tablets, Oral, 15 mg, Weekly, 48 weeks; Drug: Methotrexate; Tablets, Oral, 15 mg, Weekly, Week 25 - Week 48 only; Drug: Adalimumab Placebo; Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks
Experimental: Arm 5; BMS-945429 + Methotrexate/Methotrexate Placebo + Adalimumab Placebo	Biological: BMS-945429; Injection, Subcutaneous, 25 mg, Every 4 weeks, Day 1 - Week 24 only; Biological: BMS-945429; Injection, Subcutaneous, 100 mg, Every 4 weeks, 48 weeks; Biological: BMS-945429; Injection, Subcutaneous, 200 mg, Every 4 weeks, Week 25 - Week 48; Biological: BMS-945429; Injection, Subcutaneous, 200 mg, Every 4 weeks, 48 weeks; Drug: Methotrexate; Tablets, Oral, 15 mg, Weekly, Day 1 - Week 24 only; Drug: Methotrexate; Tablets, Oral, 15 mg, Weekly, 48 weeks; Drug: Methotrexate; Tablets, Oral, 15 mg, Weekly, Week 25 - Week 48 only; Drug: Adalimumab Placebo; Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks; Drug: Methotrexate Placebo; Tablets, Oral, 0 mg, Weekly, Day 1 - Week 24 only
Experimental: Arm 6; BMS-945429 + Methotrexate/Methotrexate Placebo+Adalimumab Placebo	Biological: BMS-945429; Injection, Subcutaneous, 25 mg, Every 4 weeks, Day 1 - Week 24 only; Biological: BMS-945429; Injection, Subcutaneous, 100 mg, Every 4 weeks, 48 weeks; Biological: BMS-945429; Injection, Subcutaneous, 200 mg, Every 4 weeks, Week 25 - Week 48; Biological: BMS-945429; Injection, Subcutaneous, 200 mg, Every 4 weeks, 48 weeks; Drug: Methotrexate; Tablets, Oral, 15 mg, Weekly, Day 1 - Week 24 only; Drug: Methotrexate; Tablets, Oral, 15 mg, Weekly, 48 weeks; Drug: Methotrexate; Tablets, Oral, 15 mg, Weekly, Week 25 - Week 48 only; Drug: Adalimumab Placebo; Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks; Drug: Methotrexate Placebo; Tablets, Oral, 0 mg, Weekly, Day 1 - Week 24 only
Active Comparator: Arm 7; Adalimumab + Methotrexate	Drug: Methotrexate; Tablets, Oral, 15 mg, Weekly, Day 1 - Week 24 only; Drug: Methotrexate; Tablets, Oral, 15 mg, Weekly, 48 weeks; Drug: Methotrexate; Tablets, Oral, 15 mg, Weekly, Week 25 - Week 48 only; Drug: Adalimumab; Injection, Subcutaneous, 40 mg, Every 2 weeks, 48 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Participants Achieving an American College of Rheumatology (ACR) 20% Response Rate	The ACR20/50/70 is a composite measure defined as both improvement of 20%, 50% or 70% in the number of tender and number of swollen joints, and a 20%, 50% or 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).	At 12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Participants With ACR 20 Response	The ACR20/50/70 is a composite measure defined as both improvement of 20%, 50% or 70% in the number of tender and number of swollen joints, and a 20%, 50% or 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).	At 24 weeks
Percent of Participants Achieving ACR 50 Response Rate	The ACR20/50/70 is a composite measure defined as both improvement of 20%, 50% or 70% in the number of tender and number of swollen joints, and a 20%, 50% or 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).	At weeks 12 and 24
Percent of Participants Achieving ACR 70 Response Rate	The ACR20/50/70 is a composite measure defined as both improvement of 20%, 50% or 70% in the number of tender and number of swollen joints, and a 20%, 50% or 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).	At weeks 12 and 24
Mean Change From Baseline in Disease Activity as Measured by Disease Activity Score 28 C-reactive Protein (DAS28-CRP)	DAS28-CRP = Disease Activity Scores 28 based on C Reactive Protein. A DAS28-CRP below 2.6 is interpreted as remission.	Baseline, weeks 12 and 24
Percent of Participants With Remission by DAS28-CRP	DAS28-CRP = Disease Activity Scores 28 based on C Reactive Protein. A DAS28-CRP below 2.6 is interpreted as remission.	At weeks 12 and 24
Mean Change From Baseline in Clinical Disease Activity Index (CDAI)	CDAI is a composite index for assessing disease activity. CDAI is based on the simple summation of the count of swollen joint count (SCJ) (0-28) and tender joint count (TJC) (0-28) along with patient global assessment (0-10) Scale and physician global assessment (0-10) for estimating disease activity where 10 means maximal activity. The CDAI has a range from 0 to 76. CDAI <= 2.8 = Remission CDAI > 2.8 and <= 10 = Low Disease Activity CDAI > 10 and <= 22 = Moderate Disease Activity CDAI > 22 = High Disease Activity	Baseline, weeks 12 and 24
Percent of Participants With Remission by CDAI	CDAI is a composite index for assessing disease activity. CDAI is based on the simple summation of the count of swollen joint count (SCJ) (0-28) and tender joint count (TJC) (0-28) along with patient global assessment (0-10) Scale and physician global assessment (0-10) for estimating disease activity where 10 means maximal activity. The CDAI has a range from 0 to 76. CDAI <= 2.8 = Remission CDAI > 2.8 and <= 10 = Low Disease Activity CDAI > 10 and <= 22 = Moderate Disease Activity CDAI > 22 = High Disease Activity	At weeks 12 and 24
Mean Change From Baseline in Simplified Disease Activity Index (SDAI)	SDAI is a composite index for assessing disease activity. CDAI is based on the simple summation of the count of swollen joint count (0-28) and tender joint count (0-28) along with patient global assessment (0-10) Scale and physician global assessment (0-10) for estimating disease activity where 10 means maximal activity and C-reactive protein (0-10). The SDAI has a range from 0 to 86. 0.0 - 3.3 = Remission 3.4 - 11.0 = Low Activity 11.1 - 26.0 = Moderate Activity 26.1 - 86.0 = High Activity	Baseline, weeks 12 and 24
Percent of Participants With Remission by SDAI	SDAI is a composite index for assessing disease activity. CDAI is based on the simple summation of the count of swollen joint count (0-28) and tender joint count (0-28) along with patient global assessment (0-10) Scale and physician global assessment (0-10) for estimating disease activity where 10 means maximal activity and C-reactive protein (0-10). The SDAI has a range from 0 to 86. 0.0 - 3.3 = Remission 3.4 - 11.0 = Low Activity 11.1 - 26.0 = Moderate Activity 26.1 - 86.0 = High Activity	At weeks 12 and 24
Percent of Participants With Remission Rate by Boolean Definition	Boolean-based definition: At any time point, a patient must satisfy all of the following: TJC ≤1 (0-28) SJC ≤1 (0-28) CRP ≤1 mg/dl Patient Global Assessment ≤1 (on a 0-10 scale)	At weeks 12 and 24
Mean Change From Baseline in Health Assessment Questionnaire (HAQ) Disability Index	Patients report the amount of difficulty they have in performing 8 categories. Each category is scored on a scale ranging from 0 (performed without any difficulty) to 3 (cannot be done at all). The HAQ-DI is then calculated by summing the scores and dividing by the number of categories answered. Total score is between 0-3.0. Increasing scores indicate worse functioning with 0 indicating no functional impairment and 3 indicating complete impairment. The HAQ-DI cannot be calculated if the subject does not have scores for at least 6 categories. A response was defined as a subject with a reduction from baseline in HAQ-DI of at least 0.22.	Baseline, weeks 12 and 24
Mean Change From Baseline in Short Form 36 (SF-36) as Measured by Physical and Mental Components	The SF-36 questionnaire consists of eight scales yielding two summary measures: physical and mental health. The physical health measure includes four scales of physical functioning (10 items), role-physical (4 items), bodily pain (2 items), and general health (5 items). The mental health measure is composed of vitality (4 items), social functioning (2 items), role-emotional (3 items), and mental health (5 items). To score the SF-36, scales are standardized with a scoring algorithm to obtain a score ranging from 0 to 100. Higher scores indicate better health status.	Baseline, weeks 12 and 24
Mean Change From Baseline in Fatigue Severity (VAS) Score	A 9-item questionnaire with questions related to how fatigue interferes with certain activities and rates its severity according to a self-report scale. The items are scored on a 7 point scale with 1 = strongly disagree and 7= strongly agree. The minimum score = 9 and maximum score possible = 63. Higher the score = greater fatigue severity.	Baseline, weeks 12 and 24
Mean Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Scores	The WPAI yeilds four types of scores: Absenteeism (work time missed); Presenteesism (impairment at work / reduced on-the-job effectiveness); Work productivty loss (overall work impairment / absenteeism plus presenteeism); Activity Impairment WPAI outcomes are expressed as impairment percentages with each subscale score ranging from 0-100. The subscale scores are added and averaged to produce a total WPAI score between 0-100. Higher scores indicate greater impairment and less productivity.	Baseline, weeks 12 and 24
Mean Change From Baseline in Radiographic (MRI) Progression of Synovitis, Osteitis (Bone Marrow Edema), Bone Erosion and Cartilage Loss (Joint-space Narrowing)		Baseline and week 12
Mean Change From Baseline in Radiographic (X-ray) Progression of Joint Damage as Measured by Modified Sharp/Van Der Heijde Total Score	The Sharp-van der Heijde total score ranges from 0-528. Scores for erosion range from 0 to 5 in the hands and 0 to 10 in the feet and reflect erosion size, with 0 defined as no erosion and 3 defined as a large erosion passing the midline of the joint. If there is > 1 erosion per joint, scores can be combined to give a maximum score of 5 per joint in the hands and 10 per joint in the feet (a maximum of 5 at each side of the joint). Joint space narrowing scores vary from 0 to 4 in both the hands and feet, with 0 being normal and 4 being the absence of joint space with evident ankylosis or subluxation. Gross osteolysis and pencil-in-cup change are scored separately and, if present, are assigned the maximum score for erosion and joint space narrowing for the same affected joint. Higher scores indicate increased joint damage.	Baseline and week 24

Collaborators and Investigators

• Sponsor: CSL Behring

Publications and helpful links

General Publications

• Weinblatt ME, Mease P, Mysler E, Takeuchi T, Drescher E, Berman A, Xing J, Zilberstein M, Banerjee S, Emery P. The efficacy and safety of subcutaneous clazakizumab in patients with moderate-to-severe rheumatoid arthritis and an inadequate response to methotrexate: results from a multinational, phase IIb, randomized, double-blind, placebo/active-controlled, dose-ranging study. Arthritis Rheumatol. 2015 Oct;67(10):2591-600. doi: 10.1002/art.39249.

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: June 13, 2011
• First Submitted That Met QC Criteria: June 13, 2011
• First Posted (Estimate): June 14, 2011

Study Record Updates

• Last Update Posted (Actual): December 6, 2021
• Last Update Submitted That Met QC Criteria: December 3, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Adalimumab; Methotrexate
• Other Study ID Numbers: IM133-001; 2010-023956-99 (EudraCT Number)