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A Study of Tocilizumab + DMARDs in Patients With Moderate to Severe Active Rheumatoid Arthritis

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
tocilizumab [RoActemra/Actemra]
Standard DMARDs (Disease Modifying Anti Rheumatic Drugs)
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Azienda Ospedaliera Rummo; Divisione Di Reumatologia
  • Azienda Ospedaliera A. Cardarelli; Medicina III - Divisione di Reumatologia
  • UNIVERSITÀ DI NAPOLI FEDERICO II; Dipartimento di Immunologia Clinica ed Allergologia
  • Ospedale M. Scarlato - Asl Sa1; U.O. Di Reumatologia
  • Irccs Fondazione Salvatore Maugeri-Istituto Scientifico Di Telese;U.O. Riabilitazione Reumatologica
  • A.O.U Policlinico S. Orsola Malpighi di Bologna U.O di Medicina Interna Borghi - Pad.2
  • Az. Ospedaliera Univ. di Parma; Medicina Interna e Reumatologia
  • Ospedale Guglielmo Da Saliceto Unità Operativa Semplice di Reumatologia e Immunologia
  • Policlinico Tor Vergata; Divisione Di Reumatologia
  • Ospedale Nuovo Regina Margherita; Divisione di Medicina Interna Reumatologia
  • Ospedale S.Pietro Fatebenefratelli; Divisione di Reumatologia
  • Ospedale Belcolle; Divisione Di Reumatologia
  • Ospedale San Paolo; Divisione di Reumatologia
  • ASST PAPA GIOVANNI XXIII; Reumatologia Day Hospital-Torre 2 terzo piano
  • ASST DI MONZA; Reumatologia (Medicina I)
  • IRCCS Istituto Clinico Humanitas; Immunologia Clinica E Reumatologia
  • Ospedale S. Giovanni Bosco; S.C. A Direzione Uni Ria Di Immunologia Clinica
  • Ospedale Perrino; Medicina Interna - Divisione di Reumatologia
  • Presidio Ospedaliero Valle D'itria; Divisione Di Nefrologia
  • Ospedale Galateo; U.O. Di Reumatologia
  • Ospedale Vittorio Emanuele Ii; U.O. Reumatologia Clinica Medica Condorelli
  • A.U.O. G. Martino- Policlinico Univ. Gazzi; Dept. Di Medicina Interna, Divisione Di Reumatologia
  • Arnas Ospedale Civico; Medicina Interna II
  • Az. Osp. Villa Sofia; Unità Operativa Reumatologia
  • Ospedali Riuniti Villa Sofia- Cervello X; Divisione Medicina I
  • Ospedale Di Massa; Divisione Di Reumatologia
  • Ospedale SS Giovanni e Paolo; Divisione Di Reumatologia

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

Outcomes

Primary Outcome Measures

Improvement of Anemia at Week 4 Assessed as Change From Baseline in Hemoglobin
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
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
Improvement of Anemia Assessed as Change From Baseline in Hemoglobin
Improvement of anemia was evaluated as change in hemoglobin levels from baseline.
FACIT-F Scores
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
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
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
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
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
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
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
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
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)
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
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
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
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
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
Number of Days as Assessed by Short Form-Health and Labour Questionnaire (SF-HLQ)
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
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
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
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
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
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
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
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.

Full Information

First Posted
July 30, 2009
Last Updated
June 28, 2017
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT00951275
Brief Title
A Study of Tocilizumab + DMARDs in Patients With Moderate to Severe Active Rheumatoid Arthritis
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.
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
October 31, 2009 (Actual)
Primary Completion Date
July 22, 2011 (Actual)
Study Completion Date
July 22, 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
105 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
tocilizumab [RoActemra/Actemra]
Intervention Description
8mg/kg iv every 4 weeks for 6 months
Intervention Type
Drug
Intervention Name(s)
Standard DMARDs (Disease Modifying Anti Rheumatic Drugs)
Intervention Description
As prescribed
Primary Outcome Measure Information:
Title
Improvement of Anemia at Week 4 Assessed as Change From Baseline in Hemoglobin
Description
Hemoglobin levels were measured as grams/deciliter (g/dL).
Time Frame
Week 4
Title
Improvement in Fatigue at Week 4 Assessed as Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scores
Description
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.
Time Frame
Week 4
Secondary Outcome Measure Information:
Title
Mean Hemoglobin Levels During the Study
Time Frame
Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24
Title
Improvement of Anemia Assessed as Change From Baseline in Hemoglobin
Description
Improvement of anemia was evaluated as change in hemoglobin levels from baseline.
Time Frame
Weeks 2, 4, 8, 12, 16, 20, and 24
Title
FACIT-F Scores
Description
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.
Time Frame
Baseline, Weeks 2, 4, 8,12, 16, 20 and 24
Title
Improvement of Fatigue Assessed as Change From Baseline in FACIT-F Scores
Description
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.
Time Frame
Weeks 2, 4, 8, 12, 16, 20 and 24
Title
Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement
Description
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]).
Time Frame
Week 24
Title
Percent Change From Baseline to Week 24 in TJC
Description
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.
Time Frame
Week 24
Title
Percent Change From Baseline to Week 24 in SJC
Description
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.
Time Frame
Week 24
Title
Percent Change From Baseline to Week 24 in Patient Global Assessment of Pain
Description
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.
Time Frame
Week 24
Title
Percent Change From Baseline to Week 24 in Patient's Global Assessment of Disease Activity
Description
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.
Time Frame
Week 24
Title
Percent Change From Baseline to Week 24 in Investigator's Global Assessment of Disease Activity
Description
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.
Time Frame
Week 24
Title
Percent Change From Baseline to Week 24 in HAQ-DI
Description
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.
Time Frame
Week 24
Title
Percent Change From Baseline to Week 24 in High-Sensitivity CRP (Hs-CRP)
Description
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).
Time Frame
Week 24
Title
Percent Change From Baseline to Week 24 in ESR
Description
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.
Time Frame
Week 24
Title
Percentage of Participants With a Response at Week 24 by European League Against Rheumatism (EULAR) Category
Description
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.
Time Frame
Week 24
Title
Percentage of Participants With a Response at Week 24 by DAS28 Category
Description
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.
Time Frame
Week 24
Title
Percent Change From Baseline to Week 24 in DAS28 Score
Description
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.
Time Frame
Week 24
Title
Percentage of Participants With an Improvement of ≥1 g/dL in Hemoglobin
Time Frame
Week 24
Title
Number of Days as Assessed by Short Form-Health and Labour Questionnaire (SF-HLQ)
Description
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.
Time Frame
Baseline
Title
Change From Baseline to Weeks 12 and 24 in Number of Days as Assessed by SF-HLQ
Description
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.
Time Frame
Weeks 12 and 24
Title
Number of Hours as Assessed by SF-HLQ
Description
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.
Time Frame
Baseline
Title
Change From Baseline to Weeks 12 and 24 in Number of Hours as Assessed by SF-HLQ
Description
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.
Time Frame
Baseline
Title
SF-HLQ Hindrance Score
Description
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).
Time Frame
Baseline
Title
Change From Baseline to Weeks 12 and 24 SF-HLQ Hindrance Score
Description
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.
Time Frame
Baseline
Title
Efficiency as Assessed by SF-HLQ
Description
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.
Time Frame
Baseline
Title
Change From Baseline to Weeks 12 and 24 in Efficiency as Assessed by SF-HLQ
Description
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.
Time Frame
Baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Azienda Ospedaliera Rummo; Divisione Di Reumatologia
City
Benevento
State/Province
Campania
ZIP/Postal Code
82100
Country
Italy
Facility Name
Azienda Ospedaliera A. Cardarelli; Medicina III - Divisione di Reumatologia
City
Napoli
State/Province
Campania
ZIP/Postal Code
80131
Country
Italy
Facility Name
UNIVERSITÀ DI NAPOLI FEDERICO II; Dipartimento di Immunologia Clinica ed Allergologia
City
Napoli
State/Province
Campania
ZIP/Postal Code
80131
Country
Italy
Facility Name
Ospedale M. Scarlato - Asl Sa1; U.O. Di Reumatologia
City
Scafati
State/Province
Campania
ZIP/Postal Code
84018
Country
Italy
Facility Name
Irccs Fondazione Salvatore Maugeri-Istituto Scientifico Di Telese;U.O. Riabilitazione Reumatologica
City
Telese Terme
State/Province
Campania
ZIP/Postal Code
82037
Country
Italy
Facility Name
A.O.U Policlinico S. Orsola Malpighi di Bologna U.O di Medicina Interna Borghi - Pad.2
City
Bologna
State/Province
Emilia-Romagna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Az. Ospedaliera Univ. di Parma; Medicina Interna e Reumatologia
City
Parma
State/Province
Emilia-Romagna
ZIP/Postal Code
43100
Country
Italy
Facility Name
Ospedale Guglielmo Da Saliceto Unità Operativa Semplice di Reumatologia e Immunologia
City
Piacenza
State/Province
Emilia-Romagna
ZIP/Postal Code
29100
Country
Italy
Facility Name
Policlinico Tor Vergata; Divisione Di Reumatologia
City
Roma
State/Province
Lazio
ZIP/Postal Code
00133
Country
Italy
Facility Name
Ospedale Nuovo Regina Margherita; Divisione di Medicina Interna Reumatologia
City
Roma
State/Province
Lazio
ZIP/Postal Code
00153
Country
Italy
Facility Name
Ospedale S.Pietro Fatebenefratelli; Divisione di Reumatologia
City
Roma
State/Province
Lazio
ZIP/Postal Code
00189
Country
Italy
Facility Name
Ospedale Belcolle; Divisione Di Reumatologia
City
Viterbo
State/Province
Lazio
ZIP/Postal Code
01100
Country
Italy
Facility Name
Ospedale San Paolo; Divisione di Reumatologia
City
Savona
State/Province
Liguria
ZIP/Postal Code
17100
Country
Italy
Facility Name
ASST PAPA GIOVANNI XXIII; Reumatologia Day Hospital-Torre 2 terzo piano
City
Bergamo
State/Province
Lombardia
ZIP/Postal Code
24127
Country
Italy
Facility Name
ASST DI MONZA; Reumatologia (Medicina I)
City
Monza
State/Province
Lombardia
ZIP/Postal Code
20052
Country
Italy
Facility Name
IRCCS Istituto Clinico Humanitas; Immunologia Clinica E Reumatologia
City
Rozzano
State/Province
Lombardia
ZIP/Postal Code
20089
Country
Italy
Facility Name
Ospedale S. Giovanni Bosco; S.C. A Direzione Uni Ria Di Immunologia Clinica
City
Torino
State/Province
Piemonte
ZIP/Postal Code
10154
Country
Italy
Facility Name
Ospedale Perrino; Medicina Interna - Divisione di Reumatologia
City
Brindisi
State/Province
Puglia
ZIP/Postal Code
72100
Country
Italy
Facility Name
Presidio Ospedaliero Valle D'itria; Divisione Di Nefrologia
City
Martina Franca
State/Province
Puglia
ZIP/Postal Code
74015
Country
Italy
Facility Name
Ospedale Galateo; U.O. Di Reumatologia
City
San Cesario Di Lecce
State/Province
Puglia
ZIP/Postal Code
73016
Country
Italy
Facility Name
Ospedale Vittorio Emanuele Ii; U.O. Reumatologia Clinica Medica Condorelli
City
Catania
State/Province
Sicilia
ZIP/Postal Code
95124
Country
Italy
Facility Name
A.U.O. G. Martino- Policlinico Univ. Gazzi; Dept. Di Medicina Interna, Divisione Di Reumatologia
City
Gazzi
State/Province
Sicilia
ZIP/Postal Code
98125
Country
Italy
Facility Name
Arnas Ospedale Civico; Medicina Interna II
City
Palermo
State/Province
Sicilia
ZIP/Postal Code
90127
Country
Italy
Facility Name
Az. Osp. Villa Sofia; Unità Operativa Reumatologia
City
Palermo
State/Province
Sicilia
ZIP/Postal Code
90146
Country
Italy
Facility Name
Ospedali Riuniti Villa Sofia- Cervello X; Divisione Medicina I
City
Palermo
State/Province
Sicilia
ZIP/Postal Code
90146
Country
Italy
Facility Name
Ospedale Di Massa; Divisione Di Reumatologia
City
Massa
State/Province
Toscana
ZIP/Postal Code
54100
Country
Italy
Facility Name
Ospedale SS Giovanni e Paolo; Divisione Di Reumatologia
City
Venezia
State/Province
Veneto
ZIP/Postal Code
30127
Country
Italy

12. IPD Sharing Statement

Learn more about this trial

A Study of Tocilizumab + DMARDs in Patients With Moderate to Severe Active Rheumatoid Arthritis

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