An Open-label Study With Tocilizumab in Patients With Rheumatoid Arthritis in a Local Environment

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01254331
First received: December 3, 2010
Last updated: February 10, 2015
Last verified: February 2015
  Purpose

This open-label, multi-center study in a local environment will evaluate the safety and the effect on disease activity with regard to reduction in signs and symptoms over 6 months of treatment in patients with moderate to severe active rheumatoid arthritis who experienced an inadequate response to a non-biologic DMARD. Tocilizumab 8 mg/kg will be administered as an intravenous infusion every 4 weeks for a total of 6 infusions as monotherapy or in combination with methotrexate (MTX). The anticipated time of study treatment is 24 weeks.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: tocilizumab [RoActemra]
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open Label, Multicenter, Trial to Evaluate Safety, Tolerability and Efficacy of Tocilizumab in Monotherapy or in Combination With MTX in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Current Non Biologic DMARDs

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Adverse Events (AEs), Serious AEs (SAEs), Related AEs, Discontinuation Due to AEs, or Death [ Time Frame: Baseline, every 4 weeks through Week 52 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Percentage of Participants Who Achieved Clinically Significant Improvement Assessed Using Disease Activity Score Based on 28 Joints (DAS28) [ Time Frame: Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 ] [ Designated as safety issue: No ]
    DAS28 calculated from the swollen joint count (SJC) and tender joint count (TJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and participant's global assessment (PtGA) of disease activity by Visual analog Scale (VAS; participant rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 less than or equal to (≤) 3.2 equals (=) low disease activity (LDA), DAS28 greater than (>) 3.2 to 5.1 = moderate to high disease activity. A reduction of at least 1.2 units in DAS28 was considered clinically significant improvement.

  • Percentage of Participants Achieving LDA Assessed Using DAS28 [ Time Frame: Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 ] [ Designated as safety issue: No ]
    DAS28 calculated from the SJC and TJC using the 28 joints count, the ESR (mm/hour) and PtGA of disease activity (VAS) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 less than (<) 3.2 = LDA.

  • Percentage of Participants Achieving Remission Assessed Using DAS28 [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 ] [ Designated as safety issue: No ]
    DAS28 calculated from the SJC and TJC using the 28 joints count, the ESR (mm/hour) and PtGA of disease activity (VAS) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. Participants were considered in remission when reaching a DAS28 score <2.6.

  • Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) [ Time Frame: Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 ] [ Designated as safety issue: No ]
    The ACR response rates ACR20/ACR50/ACR70 are defined as ≥20%, ≥50%, or ≥70% improvement, respectively, in SJC and TJC, as well as a ≥20%, ≥50%, or ≥70% improvement, respectively, in 3 of the 5 remaining core ACR assessments: 1) physician's global assessment of disease activity, 2) participant's assessment of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) C-reactive protein (CRP) at each visit.

  • Time To Achieve ACR20/ACR50/ACR70 [ Time Frame: Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 ] [ Designated as safety issue: No ]
    The ACR response rates ACR20/ACR50/ACR70 are defined as ≥20%, ≥50%, or ≥70% improvement, respectively, in SJC and TJC, as well as a ≥20%, ≥50%, or ≥70% improvement, respectively, in 3 of the 5 remaining core ACR assessments: 1) physician's global assessment of disease activity, 2) participant's assessment of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability via (HAQ, and 5) CRP at each visit. The median time to achieve ACR20/ACR50/ACR70 was calculated using Kaplan-Meier estimates.

  • SJC and TJC [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 ] [ Designated as safety issue: No ]
    28 joints were assessed for swelling and tenderness. Joints were classified as swollen (1)/not swollen (0) and tender (1)/not tender (0) giving a total possible SJC and TJC score of 0 to 28 each.

  • Assessment of Pain by the Participant Using Visual Analog Scale (VAS) [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 ] [ Designated as safety issue: No ]
    The participants assessed their pain using a 0 to 100 millimeter (mm) horizontal VAS. 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". The participants marked the line corresponding to their level of pain and the distance from the left edge was measured.

  • Assessment of Global Disease by the Participant Using VAS [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 ] [ Designated as safety issue: No ]
    The participant's global assessment of disease activity was assessed using a 0 to 100 mm horizontal VAS by the participant. 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). The participants marked the line corresponding to their assessment of disease activity and the distance from the left edge was measured.

  • Assessment of Global Disease by the Physician Using Visual Analog Scale (VAS) [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 ] [ Designated as safety issue: No ]
    The physician's global assessment of disease activity was assessed using a 0 to 100 mm horizontal 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). The physician marked the line corresponding to their assessment of disease activity and the distance from the left edge was measured.

  • Assessment of Physical Function Using Health Assessment Questionnaire (HAQ) [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 ] [ Designated as safety issue: No ]
    Physical function was assessed using the HAQ. The HAQ scores range from 0 to 3 with, 0: no assistance needed, 1: participant uses a special device for day-to-day activities, 2: participant usually needs help from another person, and 3: participant uses BOTH a special device AND another person's help for day-to-day activities.

  • Mean C-Reactive Protein (CRP) Levels [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 ] [ Designated as safety issue: No ]
    CRP is an acute phase reactant and levels of CRP increase with inflammation. CRP is measured as milligrams per liter (mg/L).

  • Mean Erythrocyte Sedimentation Rate (ESR) Levels [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 ] [ Designated as safety issue: No ]
    ESR is an acute phase reactant and levels of ESR increase with inflammation. ESR is measured as mm/hour.

  • Percentage of Participants Experiencing Fatigue [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
  • Number of Participants Who Discontinued Tocilizumab [ Time Frame: Week 52 ] [ Designated as safety issue: No ]

Enrollment: 51
Study Start Date: February 2011
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single arm Drug: tocilizumab [RoActemra]
tocilizumab 8 mg/kg intravenous infusion every 4 weeks for a total of 6 infusions

  Eligibility

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

Inclusion Criteria:

  • Adult patients >/=18 years of age
  • Moderate to severe rheumatoid arthritis defined as DAS 28>3.2
  • Body weight </=150 kg
  • Patient on at least 1 non-biologic DMARD on a stable dose for at least 8 weeks at any time prior to study start
  • Inadequate clinical response to a stable dose of a non-biologic DMARD

Exclusion Criteria:

  • Major surgery within 8 weeks prior to screening or planned major surgery within 6 months following enrollment
  • Rheumatic autoimmune disease other than rheumatoid arthritis (RA)
  • Functional class IV as defined by the ACR classification
  • History or current inflammatory joint disease other than RA
  • Previous treatment with any cell depleting therapy
  • Previous treatment with methotrexate
  • Previous treatment with tocilizumab
  • Previous treatment with any biologic drug that is used in the treatment of RA
  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: NCT01254331

Locations
Tunisia
Sfax, Tunisia, 3000
Sousse, Tunisia, 4000
Tunis, Tunisia, 2046
Tunis, Tunisia, 1007
Tunis, Tunisia, 2010
Tunis, Tunisia, 1008
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01254331     History of Changes
Other Study ID Numbers: ML22642
Study First Received: December 3, 2010
Results First Received: February 10, 2015
Last Updated: February 10, 2015
Health Authority: Tunisia: Ministry of Health

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases

ClinicalTrials.gov processed this record on March 25, 2015