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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

  Show 152 Study Locations
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 June 18, 2013