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A Study of RoActemra/Actemra (Tocilizumab) in Combination With Methotrexate Versus RoActemra/Actemra Monotherapy in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01399697
First received: July 20, 2011
Last updated: June 18, 2015
Last verified: May 2015
  Purpose
This randomized, double-blind, parallel-group study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in combination with methotrexate versus RoActemra/Actemra monotherapy in patients with rheumatoid arthritis and an inadequate response to methotrexate. All patients will receive RoActemra/Actemra 8 mg/kg intravenously (iv) every 4 weeks plus oral methotrexate for 16 weeks. Patients achieving low disease activity at Week 16 will be randomized to receive a further 12 weeks of RoActemra/Actemra treatment plus either methotrexate or placebo. Anticipated time on study treatment is 28 weeks.

Condition Intervention Phase
Rheumatoid Arthritis
Drug: methotrexate
Drug: placebo
Drug: tocilizumab [RoActemra/Actemra]
Phase 4

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 Multi-center Study of the Safety and Effect on Disease Activity of Tocilizumab (TCZ) in Combination With MTX Versus Tocilizumab Monotherapy in Patients With Rheumatoid Arthritis, With Inadequate Response to MTX (Defined as DAS 28 > 3,2)

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Change in Disease Activity Score Based on 28-Joint Count (DAS28) From Week 16 to Week 28 [ Time Frame: Baseline, Week 16, and Week 28 ] [ Designated as safety issue: No ]
    The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis (RA). The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (erythrocyte sedimentation rate [ESR] in millimeters per hour [mm/hr]), and general health status (participant global assessment of disease activity using visual analog scale [VAS], range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.


Secondary Outcome Measures:
  • Percentage of Participants With DAS28 Score Less Than (<) 2.6 at Week 28 [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
    The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores indicate worsening. DAS28 <2.6 equals (=) remission.

  • Percentage of Participants With Clinical Disease Activity Index (CDAI) <2.8 at Week 28 [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
    CDAI is the sum of tender and swollen joint count based on 28 joints and the participant and physician global disease assessment (VAS 0-10 centimeters [cm]). CDAI total score 0-76; higher scores = greater affect due to disease activity. CDAI <2.8 = clinical remission.

  • Percentage of Participants With Simplified Disease Activity Index (SDAI) <3.3 at Week 28 [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]
    SDAI is calculated by a simple numerical sum of tender and swollen joint count (based on a 28-joint assessment), participant and physician global assessment of disease activity (VAS 0-10 cm), and level of C-reactive protein in milligram per deciliter (mg/dL). SDAI total score 0-86; higher scores = greater affect due to disease activity. SDAI <3.3 = clinical remission.

  • Change in the Health Assessment Questionnaire Disability Index (HAQ-DI) From Week 16 to Week 28 [ Time Frame: Week 16 and Week 28 ] [ Designated as safety issue: No ]
    HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.

  • Change in the Quality of Life Questionnaire (Short Form-12 [SF-12]) From Week 16 to Week 28 in Mental Health [ Time Frame: Week 16 and Week 28 ] [ Designated as safety issue: No ]
    Quality of life questionnaire (SF-12) scores were computed using the scores of 12 questions and ranged from 0 to 100, where a 0 score indicated the lowest level of health measured by the scales and 100 indicated the highest level of health. A negative change from baseline indicated decline in health and higher scores indicated improvement in health.

  • Change in the Quality of Life Questionnaire (SF-12) From Week 16 to Week 28 in Physical Health [ Time Frame: Week 16 and Week 28 ] [ Designated as safety issue: No ]
    Quality of life questionnaire (SF-12) scores were computed using the scores of 12 questions and ranged from 0 to 100, where a 0 score indicated the lowest level of health measured by the scales and 100 indicated the highest level of health. A negative change from baseline indicated a worsening of quality of life.

  • Change From Week 16 to Week 28 in Global Assessment of Disease Activity as Assessed With the Visual Analogue Scale (VAS) Performed by Participant [ Time Frame: Week 16 and Week 28 ] [ Designated as safety issue: No ]
    Participants were asked to rate their global assessment of disease activity on a scale ranging from 0=very good to 100=very bad. The scale was represented by a line with 0 at the left edge and 100 at the right edge. The participant was asked to mark the line corresponding to the assessment of their disease activity. The distance from the left edge was measured in mm.

  • Change From Week 16 to Week 28 in Global Assessment of Disease Activity Assessed Using the VAS Performed by the Investigator [ Time Frame: Week 16 and Week 28 ] [ Designated as safety issue: No ]
    Participants were asked to rate their global assessment of disease activity on a scale ranging from 0=very good to 100=very bad. The scale was represented by a line with 0 at the left edge and 100 at the right edge. The participant was asked to mark the line corresponding to the assessment of their disease activity. The distance from the left edge was measured in mm.


Enrollment: 261
Study Start Date: September 2011
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: methotrexate
orally, Week 1 - 16
Drug: methotrexate
orally, Week 17-28
Drug: tocilizumab [RoActemra/Actemra]
8 mg/kg iv every 4 weeks, 28 weeks
Active Comparator: B Drug: methotrexate
orally, Week 1 - 16
Drug: placebo
methotrexate placebo orally, Week 17-28
Drug: tocilizumab [RoActemra/Actemra]
8 mg/kg iv every 4 weeks, 28 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients, >/= 18 years of age
  • Active moderate to severe rheumatoid arthritis (DAS28 >/= 3.2) at baseline
  • Currently receiving methotrexate for at least 12 weeks, at a stable oral dose of at least 15 mg/week for at least 6 weeks prior to treatment (Day 1)
  • Body weight < 150 kg
  • Oral corticoids must have been at stable dose for at least 25 out of 28 days prior to baseline; maximum dose 10 mg/day

Exclusion Criteria:

  • Pregnant or nursing women
  • Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months after baseline
  • Rheumatic autoimmune disease other than RA
  • Functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in Rheumatoid Arthritis
  • Prior history of or current inflammatory joint disease other than RA
  • Treatment with a biologic agent at any time prior to baseline
  • Treatment with traditional DMARDs other than methotrexate within 1 month (for leflunomide 3 months) prior to baseline
  • Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline
  • Previous treatment with RoActemra/Actemra
  • History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
  • Known active current or history of recurrent infection
  • History of or currently active primary or secondary immunodeficiency
  • Active tuberculosis requiring treatment within the previous 3 years
  • Positive for HIV infection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01399697

  Show 54 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01399697     History of Changes
Other Study ID Numbers: ML27828 
Study First Received: July 20, 2011
Results First Received: June 18, 2015
Last Updated: June 18, 2015
Health Authority: Spain: Agencia Espanola del Medicamento y Productos Sanitarios (AEMPS)

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
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 September 30, 2016