A Study of Tocilizumab + DMARDs 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:
NCT00951275
First received: July 30, 2009
Last updated: July 22, 2014
Last verified: July 2014
  Purpose

This single arm study will assess the effect of tocilizumab + DMARDs (Disease Modifying Anti-Rheumatic Drugs)on improvement of anemia and fatigue in patients with moderate to severe active rheumatoid arthritis. Eligible patients who have had an inadequate response to DMARDs will receive tocilizumab 8mg/kg iv every 4 weeks in combination with standard DMARDs, for 6 months. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: tocilizumab [RoActemra/Actemra]
Drug: Standard DMARDs (Disease Modifying Anti Rheumatic Drugs)
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: A Single Arm, Open-label Study of Early Improvement of Anemia and Fatigue During Treatment With Tocilizumab (TCZ) in Combination With DMARDs, in Adult Patients With Moderate to Severe Active Rheumatoid Arthritis.

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Improvement of Anemia at Week 4 Assessed as Change From Baseline in Hemoglobin [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    Hemoglobin levels were measured as grams/deciliter (g/dL).

  • Improvement in Fatigue at Week 4 Assessed as Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scores [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participants fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). Clinically relevant improvement is defined as a greater than or equal to (≥)5-point change from Baseline.


Secondary Outcome Measures:
  • Mean Hemoglobin Levels During the Study [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
  • Improvement of Anemia Assessed as Change From Baseline in Hemoglobin [ Time Frame: Weeks 2, 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    Improvement of anemia was evaluated as change in hemoglobin levels from baseline.

  • FACIT-F Scores [ Time Frame: Baseline, Weeks 2, 4, 8,12, 16, 20 and 24 ] [ Designated as safety issue: No ]
    The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participants fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). Clinically relevant improvement is defined as a ≥5-point change from Baseline.

  • Improvement of Fatigue Assessed as Change From Baseline in FACIT-F Scores [ Time Frame: Weeks 2, 4, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: No ]
    The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participants fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). Clinically relevant improvement is defined as a ≥5-point change from Baseline.

  • Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The ACR response rates ACR20, ACR50, and ACR70 were defined as ≥20%, ≥50% and ≥ 70% improvement, respectively, in: swollen joint count (SJC) (66 joints) and tender joint count (TJC) (68 joints) and 3 of the 5 remaining ACR parameters: Patient assessment of pain; Patient Global Assessment of Disease Activity; Investigator Global Assessment of Disease Activity; participant self-rated assessment of disability measured by the Health Assessment Questionnaire Disability Index (HAQ-DI); and acute phase response (erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP]).

  • Percent Change From Baseline to Week 24 in TJC [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Sixty-eight (68) joints were assessed at each visit for tenderness; joints were assessed and classified as tender/not tender. Tender joint count 68 (TJC-68) was calculated as the number of tender joints from 68 joints; the number of tender joints was summed (maximum score 68). Calculated values were used for the analysis. A negative score indicated improvement.

  • Percent Change From Baseline to Week 24 in SJC [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Sixty-six (66) joints were assessed at each visit for swelling; joints were assessed and classified as swollen/not swollen. Swollen joint count 66 (SJC-66) was calculated as the number of swollen joints from 66 joints; the number of swollen joints was summed (maximum score 66). Calculated values were used for the analysis. A negative score indicated improvement.

  • Percent Change From Baseline to Week 24 in Patient Global Assessment of Pain [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The participant's assessment of their current level of pain was displayed on a 100-millimeter (mm) horizontal visual analog scale (VAS). The left-hand extreme of the line was described as "no pain" and the right-hand as "unbearable pain". The participant was asked to mark the line that corresponded to their current level of pain; the distance from the left edge was recorded.

  • Percent Change From Baseline to Week 24 in Patient's Global Assessment of Disease Activity [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The participant's overall assessment of their current disease activity was displayed on a 100-mm horizontal VAS. The left-hand extreme of the line was described as "no disease activity" (symptom free and no arthritis symptoms) and the right-hand extreme as "maximum disease activity" (maximum arthritis disease activity). Participants were asked to assess their current level of disease activity and mark the line; the distance from the left edge was recorded.

  • Percent Change From Baseline to Week 24 in Investigator's Global Assessment of Disease Activity [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The physician's assessment of the participant's current disease activity was displayed on a 100-mm horizontal VAS. The left-hand extreme of the line was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme was considered "maximum disease activity". The physician's global assessment of disease activity was completed by the Efficacy Assessor who could or could not be a physician. The assessor was asked to mark the line corresponding to their assessment of the participant's present level of disease activity; the distance from the left edge was recorded.

  • Percent Change From Baseline to Week 24 in HAQ-DI [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    HAQ-DI includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Overall score was computed as the sum of the domain scores and divided by the number of domains answered. Total possible score range was 0-3 where 0 (equals)=without difficulties; 1= with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all.

  • Percent Change From Baseline to Week 24 in High-Sensitivity CRP (Hs-CRP) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    hs-CRP is an acute phase reactant protein that is a clinical marker for Rheumatoid Arthritis (RA). hsCRP is measured in milligrams per liter (mg/L).

  • Percent Change From Baseline to Week 24 in ESR [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    ESR is a blood test used to monitor therapy in inflammatory diseases such as RA and reflects acute phase reactant levels. ESR is measured in mm per hour (mm/hr); active disease in RA is defined by an ESR greater than 30 mm/hr.

  • Percentage of Participants With a Response at Week 24 by European League Against Rheumatism (EULAR) Category [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Disease response was assessed using EULAR Disease Activity Score Based on 28-Joint Count (DAS28) categories of Good, Moderate, or No Response. Good response was defined as a DAS28 score of less than (<)3.2 and improvement from baseline of >1.2; Moderate response was defined as a DAS28 score of 3.2-5.1 and improvement from baseline of 1.2-0.6 or a DAS28 score of >5.1 and improvement from baseline of >1.2; No response was defined as a DAS28 score of >5.1 and improvement from baseline of <1.2. Participants who discontinued prematurely were identified as non-responders.

  • Percentage of Participants With a Response at Week 24 by DAS28 Category [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    DAS28 calculated from the number of swollen joints (SJC) and tender joints (TJC) using the 28 joints count, the ESR (mm/hr) and patient's global assessment of disease activity (participant rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 ≤3.2=low disease activity, DAS28 >5.1=high disease activity and DAS <2.6=remission.

  • Percent Change From Baseline to Week 24 in DAS28 Score [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    DAS28 calculated from the number of swollen joints (SJC) and tender joints (TJC) using the 28 joints count, the ESR (mm/hr) and patient's global assessment of disease activity (participant rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 ≤3.2=low disease activity, DAS28 >5.1=high disease activity and DAS <2.6=remission.

  • Percentage of Participants With an Improvement of ≥1 g/dL in Hemoglobin [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Number of Days as Assessed by Short Form-Health and Labour Questionnaire (SF-HLQ) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The SF-HLQ assessed productivity losses related to health problems in individuals with paid or unpaid work and consists of three modules (absenteeism from paid work, production losses without absenteeism from paid work and hindrance in the performance of paid and unpaid work). Any missed working days or number of worked days with reduced efficiency during the last month were reported.

  • Change From Baseline to Weeks 12 and 24 in Number of Days as Assessed by SF-HLQ [ Time Frame: Weeks 12 and 24 ] [ Designated as safety issue: No ]
    The SF-HLQ assessed productivity losses related to health problems in individuals with paid or unpaid work and consists of three modules (absenteeism from paid work, production losses without absenteeism from paid work and hindrance in the performance of paid and unpaid work). Any missed working days or number of worked days with reduced efficiency during the last month were reported.

  • Number of Hours as Assessed by SF-HLQ [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Number of working hours lost, and number of hours of support in in taking over and performing usual household tasks in the last month: chores done by family members, chores done by other persons receiving no pay, home care, other paid care, total number of unpaid hours, and total number of hours during the last month were reported.

  • Change From Baseline to Weeks 12 and 24 in Number of Hours as Assessed by SF-HLQ [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Number of working hours lost, and number of hours of support in in taking over and performing usual household tasks in the last month: chores done by family members, chores done by other persons receiving no pay, home care, other paid care, total number of unpaid hours, and total number of hours during the last month were reported. Changes from baseline were only calculated in participants who completed the questionnaire at all times (baseline, Week 12, and Week 24). Negative number indicates improvement.

  • SF-HLQ Hindrance Score [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Participants were asked if their health problems hindered their paid work on a scale of 1 to 3 (1=no, 2=yes, slightly, 3=yes, very much) and their unpaid work including household work, going shopping, odd jobs, specific activities sharing the household on a scale of 0 to 3 (0=performed without being bothered by healthy problems; 1=performed although bothered by health problems; 2=not performed because of health problems; 3=not performed for reasons other than health problems). The total hindrance score for unpaid work was derived by adding up the item scores. This hindrance score is a measure of the hindrance experienced as a result of health problems during the performance of unpaid work. The minimum score per item for hindrance score was 0, maximum score was 2 (Score of 3 was not considered since the reasons were "other than health problems"). Total score was calculated by adding all 4 items together and ranged from 0 (best possible score) to 8 (worst possible score).

  • Change From Baseline to Weeks 12 and 24 SF-HLQ Hindrance Score [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Participants were asked if health problems hindered their paid work on a scale of 1 to 3 (1=no, 2=yes, slightly, 3=yes, very much) and their unpaid work including household work, going shopping, odd jobs, specific activities sharing the household on a scale of 0 to 3 (0=performed without being bothered by healthy problems; 1=performed although bothered by health problems; 2=not performed because of health problems; 3=not performed for reasons other than health problems). Hindrance score is a measure of the hindrance experienced as a result of health problems during the performance of unpaid work. The minimum score per item for hindrance score was 0, maximum score was 2 (Score of 3 was not considered since the reasons were "other than health problems"). Total score was calculated by adding all 4 items together and ranged from 0 (best possible score) to 8 (worst possible score). A negative change from baseline indicates improvement.

  • Efficiency as Assessed by SF-HLQ [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Participants were ask to rate their efficiency in working on a scale of of 0 to 10 (0=very worse, 10=as usual). Overall efficiency score was based on the first 6 items of Question 6, which is a descriptive instrument comprised of 7 items designed to evaluate the specific problems affecting production. These 7 items relate to the effect of health problems on concentration, work pace, the need to be alone, making decisions, postponing and transferring work to others. The participant can choose from 4 possible answers: (almost) never, sometimes, often and (nearly) always. Efficiency score range=6 to 24; higher scores indicate higher impairment.

  • Change From Baseline to Weeks 12 and 24 in Efficiency as Assessed by SF-HLQ [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Participants were ask to rate their efficiency in working on a scale of of 0 to 10 (0=very worse, 10=as usual). Overall efficiency score was based on the first 6 items of Question 6, which is a descriptive instrument comprised of 7 items designed to evaluate the specific problems affecting production. These 7 items relate to the effect of health problems on concentration, work pace, the need to be alone, making decisions, postponing and transferring work to others. The participant can choose from 4 possible answers: (almost) never, sometimes, often and (nearly) always. Efficiency score range=6 to 24; higher scores indicate higher impairment. Change from baseline was only calculated for participants who completed the questionnaire at all times (baseline, Week 12 and Week 24). A negative change from baseline indicates improvement.


Enrollment: 105
Study Start Date: October 2009
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: tocilizumab [RoActemra/Actemra]
8mg/kg iv every 4 weeks for 6 months
Drug: Standard DMARDs (Disease Modifying Anti Rheumatic Drugs)
As prescribed

  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;
  • rheumatoid arthritis >=6 months duration;
  • DAS28>=3.2;
  • inadequate response to prior treatment with a stable dose (>=8 weeks) of DMARD therapy.

Exclusion Criteria:

  • rheumatic autoimmune disease other than rheumatoid arthritis;
  • history of or current inflammatory joint disease other than rheumatoid arthritis;
  • unsuccessful treatment with an anti-TNF agent;
  • previous/concurrent treatment with any cell-depleting therapies.
  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: NCT00951275

Locations
Italy
Benevento, Campania, Italy, 82100
Napoli, Campania, Italy, 80131
Scafati, Campania, Italy, 84018
Telese Terme, Campania, Italy, 82037
Bologna, Emilia-Romagna, Italy, 40138
Parma, Emilia-Romagna, Italy, 43100
Piacenza, Emilia-Romagna, Italy, 29100
Roma, Lazio, Italy, 00189
Roma, Lazio, Italy, 00153
Roma, Lazio, Italy, 00133
Viterbo, Lazio, Italy, 01100
Savona, Liguria, Italy, 17100
Bergamo, Lombardia, Italy, 24127
Monza, Lombardia, Italy, 20052
Rozzano, Lombardia, Italy, 20089
Torino, Piemonte, Italy, 10154
Brindisi, Puglia, Italy, 72100
Martina Franca, Puglia, Italy, 74015
San Cesario Di Lecce, Puglia, Italy, 73016
Catania, Sicilia, Italy, 95124
Gazzi, Sicilia, Italy, 98125
Palermo, Sicilia, Italy, 90146
Palermo, Sicilia, Italy, 90127
Massa, Toscana, Italy, 54100
Venezia, Veneto, Italy, 30127
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: NCT00951275     History of Changes
Other Study ID Numbers: ML22462, 2009-011105-17
Study First Received: July 30, 2009
Results First Received: June 4, 2014
Last Updated: July 22, 2014
Health Authority: Italy: The Italian Medicines Agency

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014