Text Size

A Study to Assess the Effect of Tocilizumab + Methotrexate on Prevention of Structural Joint Damage in Patients With Moderate to Severe Active Rheumatoid Arthritis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00106535
First received: March 25, 2005
Last updated: December 18, 2012
Last verified: December 2012
History of Changes
  Purpose

This 3 arm study will compare the safety and efficacy, with respect to prevention of joint damage, of tocilizumab versus placebo in combination with methotrexate (MTX) in patients with moderate to severe active rheumatoid arthritis. Patients will be randomized to receive tocilizumab 4mg iv, tocilizumab 8mg iv or placebo iv, every 4 weeks. All patients will also receive methotrexate, 10-25mg/week. The anticipated time on study treatment is 1-2 years and the target sample size is 500+ individuals.


Condition Intervention Phase
Rheumatoid Arthritis
 Drug: tocilizumab [RoActemra/Actemra]
Drug: Placebo
Drug: Methotrexate
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind Study of Safety and Prevention of Structural Joint Damage During Treatment With Tocilizumab Versus Placebo, in Combination With Methotrexate, in Patients With Moderate to Severe Rheumatoid Arthritis

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Patients With American College of Rheumatology-ACR20 Response [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    A positive ACR20 response requires at least a 20% improvement compared to baseline in both tender and swollen joint counts, as well as in 3 out of 5 of the additional ACR core set variables: physician's global assessment of disease activity, patient's global assessment of disease activity, patient's assessment of pain, Health Assessment Questionnaire Disability Index (HAQ-DI) and an acute phase reactant (C-Reactive Protein (CRP)) or Erythrocyte Sedimentation rate (ESR).


Secondary Outcome Measures:
  • Percentage of Patients With ACR50 Response [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The ACR50 responses require a 50% improvement relative to baseline for the same criteria as ACR20 (primary outcome measure)

  • Percentage of Patients With ACR70 Response [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The ACR70 responses require a 70% improvement relative to baseline for the same criteria as ACR20 (primary outcome measure)

  • Swollen Joint Count (66 Joint Count): Mean Change From Baseline at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    66 joints are assessed for swelling and joints are classified as swollen/not swollen giving a total swollen joint count score out of 66.

  • Tender Joint Count (68 Joint Count): Mean Change From Baseline at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total tender joint count score out of 68

  • Patient's Global Visual Analog Scale (VAS): Mean Change From Baseline at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The patient's global assessment of disease activity is assessed on a 0 to 100 mm horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity).

  • Physician's Global VAS: Mean Change From Baseline at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The physician's global assessment of disease activity is assessed on a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as "maximum disease activity" (maximum arthritis disease activity).

  • Patient's Pain VAS: Mean Change From Baseline at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The patient's assessment of pain is assessed on a 0 to 100 mm horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain".

  • C-Reactive Protein (CRP): Mean Change From Baseline at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The serum concentration of C-Reactive Protein (CRP) is measured in mg/dL. A reduction in the level is considered an improvement.

  • Erythrocyte Sedimentation Rate: Mean Change From Baseline at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The Erythrocyte Sedimentation Rate (ESR) will be measured in mm/hr. A reduction in the level is considered an improvement.

  • Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    HAQ-DI is a self-completed pt questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 poss. responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. Calculate HAQ-DI the pt must have a domain score for at least 6 of 8 domains. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score(in range 6-8). Total poss. minimum/maximum 0-8.


Enrollment: 1196
Study Start Date: January 2005
Study Completion Date: July 2012
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: tocilizumab [RoActemra/Actemra]
4mg/kg iv / month
Drug: Methotrexate
10-25mg / week
Experimental: 2 Drug: tocilizumab [RoActemra/Actemra]
8mg/kg iv / month
Drug: Methotrexate
10-25mg / week
Placebo Comparator: 3 Drug: Placebo
iv / month
Drug: Methotrexate
10-25mg / week

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • adult patients at least 18 years of age with moderate to severe active RA for at least 6 months;
  • inadequate response to a stable dose of MTX;
  • patients of reproductive potential must be using reliable methods of contraception.

Exclusion Criteria:

  • major surgery (including joint surgery) within 8 weeks before entering study, or planned surgery within 6 months after entering study;
  • prior treatment failure with an anti-tumor necrosis factor agent;
  • women who are pregnant or breast-feeding.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00106535

  Hide Study Locations
Locations
United States, Alabama
Birmingham, Alabama, United States, 35233-7333
Huntsville, Alabama, United States, 35801
United States, Arizona
Scottsdale, Arizona, United States, 85251
Tucson, Arizona, United States, 85724
United States, California
Anaheim, California, United States, 92801
Long Beach, California, United States, 90806
Los Angeles, California, United States, 90095
San Diego, California, United States, 92108
San Francisco, California, United States, 94118
Santa Maria, California, United States, 93454
Torrance, California, United States, 90505
United States, Colorado
Boulder, Colorado, United States, 80304
Colorado Springs, Colorado, United States, 80910
Denver, Colorado, United States, 80230
United States, Florida
Aventura, Florida, United States, 33180
Fort Lauderdale, Florida, United States, 33334
Tampa, Florida, United States, 33614
West Palm Beach, Florida, United States, 33407
United States, Idaho
Boise, Idaho, United States, 83702
Coeur D'alene, Idaho, United States, 83814
Idaho Falls, Idaho, United States, 83404
Meridan, Idaho, United States, 83642
United States, Illinois
Chicago, Illinois, United States, 60612-3824
Rockford, Illinois, United States, 61103
United States, Indiana
Indianapolis, Indiana, United States, 46202-5100
United States, Kentucky
Lexington, Kentucky, United States, 40515
United States, Maryland
Frederick, Maryland, United States, 21702
Hagerstown, Maryland, United States, 21740
Wheaton, Maryland, United States, 20902
United States, Missouri
Saint Louis, Missouri, United States, 63131
St Louis, Missouri, United States, 63141
United States, Montana
Billings, Montana, United States, 59101
Missoula, Montana, United States, 59802
United States, Nevada
Reno, Nevada, United States, 89502
United States, New Hampshire
Dover, New Hampshire, United States, 03820
United States, New Jersey
Medford, New Jersey, United States, 08055
Voorhees, New Jersey, United States, 08043
United States, New York
Albany, New York, United States, 12206
Brooklyn, New York, United States, 11201
Lake Success, New York, United States, 11042
New York, New York, United States, 10016
Stony Brook, New York, United States, 11794-8161
United States, North Carolina
Asheville, North Carolina, United States, 28801
Charlotte, North Carolina, United States, 28211
Raleigh, North Carolina, United States, 27609
Wilmington, North Carolina, United States, 28401
United States, Ohio
Canton, Ohio, United States, 44718
United States, Oklahoma
Oklahoma City, Oklahoma, United States, 73109
Tulsa, Oklahoma, United States, 74135
United States, Oregon
Eugene, Oregon, United States, 97401
United States, Pennsylvania
Bethlehem, Pennsylvania, United States, 18015
Duncansville, Pennsylvania, United States, 16635
Philadelphia, Pennsylvania, United States, 19140
Wyomissing, Pennsylvania, United States, 19610
United States, South Carolina
Columbia, South Carolina, United States, 29204
United States, Tennessee
Nashville, Tennessee, United States, 37203
United States, Texas
Dallas, Texas, United States, 75231
San Antonio, Texas, United States, 78217
United States, Washington
Olympia, Washington, United States, 98502
Seattle, Washington, United States, 98104
United States, Wisconsin
Glendale, Wisconsin, United States, 53217
Australia
Adelaide, Australia, 5011
Malvern, Australia, 3144
Melbourne, Australia, 3168
New Lambton, Australia, 2305
Shenton Park, Australia, 6008
St. Leonards, Australia, 2139
Brazil
Porto Alegre, Brazil, 91350-200
Rio de Janeiro, Brazil, 20551-030
Sao Paulo, Brazil, 01221-020
Sao Paulo, Brazil, 04026-000
Sao Paulo, Brazil, 5403900
China
Beijing, China, 100032
Beijing, China, 100044
Nanjing, China, 210008
Shanghai, China, 200433
Shanghai, China, 200127
Denmark
Hellerup, Denmark, 2900
Odense, Denmark, 5000
Finland
Heinola, Finland, 18120
Helsinki, Finland, 00290
Oulu, Finland, 90029
Vantaa, Finland, 01400
France
Amiens, France, 80054
Bobigny, France, 93009
Bois Guillaume, France, 76233
Bordeaux, France, 33076
Le Kremlin Bicetre, France, 94270
Lille, France, 59037
Nice, France, 06202
Orleans, France, 45000
Paris, France, 75651
Paris, France, 75877
Strasbourg, France, 67098
Toulouse, France, 31059
Vandoeuvre-les-nancy, France, 54511
Greece
Athens, Greece, 11527
Athens, Greece, 15121
Athens, Greece, 15127
Heraklion, Greece, 71110
Italy
Brescia, Italy, 25123
Coppito, Italy, 67100
Firenze, Italy, 50139
Genova, Italy, 16132
Milano, Italy, 20122
Milano, Italy, 20157
Napoli, Italy, 80131
Padova, Italy, 35128
Pavia, Italy, 27100
Pisa, Italy, 56100
Reggio Emilia, Italy, 42100
Roma, Italy, 00161
Torino, Italy, 10128
Udine, Italy, 33100
Valeggio Sul Mincio, Italy, 37067
Varese, Italy, 21100
Verona, Italy, 37134
Mexico
Chihuahua, Mexico, 31000
Mexico City, Mexico, 06726
Mexico City, Mexico, 07360
Mexico City, Mexico, 03100
Miexico City, Mexico, 06700
Monterrey, Mexico, 64460
Obregon, Mexico, 85000
Norway
Haugesund, Norway, 5528
Lillehammer, Norway, 2609
Tromsø, Norway, 9038
Poland
Bydgoszcz, Poland, 85-168
Dzialdowo, Poland, 13-200
Elblag, Poland, 82-300
Kalisz, Poland, 62-800
Krakow, Poland, 30-119
Krakow, Poland, 30-510
Poznan, Poland, 60-218
Szczecin, Poland, 71-252
Ustron, Poland, 43-450
Warszawa, Poland, 02-637
Warszawa, Poland, 00-909
Puerto Rico
Ponce, Puerto Rico, 00716
San Juan, Puerto Rico, 00936-5067
South Africa
Cape Town, South Africa, 4001
Cape Town, South Africa, 7405
Cape Town, South Africa, 7500
Diepkloof, South Africa, 1862
Spain
Barcelona, Spain, 08036
Cádiz, Spain, 11009
Merida, Spain, 97500
Sabadell, Spain, 08208
Santander, Spain, 39008
Sevilla, Spain, 41009
Switzerland
Lausanne, Switzerland, 1011
St. Gallen, Switzerland, 9007
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided by Hoffmann-La Roche

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00106535     History of Changes
Other Study ID Numbers: WA17823
Study First Received: March 25, 2005
Results First Received: February 9, 2010
Last Updated: December 18, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
 Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on May 21, 2013