TORPEDO Study: A Study on Rapid Effect of Tocilizumab in Patients With Rheumatoid Arthritis With an Inadequate Response to Disease-Modifying Antirheumatic Drugs (DMARDs) or Anti-TNF

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00977106
First received: August 18, 2009
Last updated: September 15, 2014
Last verified: September 2014
  Purpose

This study will assess the onset and maintenance of effect of tocilizumab on relief in patients with active moderate or severe rheumatoid arthritis who have had an inadequate response to DMARDs or anti-TNF. For the first, double-blind, part of the study patients will be randomized to receive an iv infusion of either 8mg/kg tocilizumab or placebo. After 4 weeks this will be followed by 11 months treatment with tocilizumab 8mg/kg iv infusion every 4 weeks. Methotrexate or DMARD therapy will be continued throughout study treatment. Target sample size is >100.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: tocilizumab [RoActemra/Actemra]
Drug: placebo
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: Comparative Double Blind Placebo Controlled Clinical Study on Tocilizumab Rapid Efficacy on Patients Relief in rheumatoïd Arthritis With an Inadequate Response to DMARDs or Anti TNF :TORPEDO

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Clinically Significant Improvement in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 4 [ Time Frame: Week 4 ] [ 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. Scoring was as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1= with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3. Relevant clinical improvement was defined as a reduction of at least 0.22 points in HAQ-DI.


Secondary Outcome Measures:
  • Patient Global Assessment of Disease Activity During the Double-Blind Treatment Period [ Time Frame: Baseline, Weeks 1 and 4 ] [ Designated as safety issue: No ]
    Participants were asked to rate their assessment of disease activity using a visual analog scale (VAS) of 0 to 100 millimeters (mm), where 0 represented no symptoms and 100 represented severe symptoms. Participants were asked to mark the line corresponding to their assessment and the distance from the left edge was measured. A negative value in change from Baseline indicates an improvement.

  • Patient Global Assessment of Disease Activity During the Open Treatment Period [ Time Frame: Baseline, Weeks 12, 24, 36 and 48 ] [ Designated as safety issue: No ]
    Participants were asked to rate their assessment of disease activity using a VAS of 0 to 100 mm, where 0 represented no symptoms and 100 represented severe symptoms. Participants were asked to mark the line corresponding to their assessment and the distance from the left edge was measured. A negative value in change from Baseline indicates an improvement.

  • Physician Global Assessment of Disease Activity During the Double-Blind Treatment Period [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
    Physicians were asked to assess disease activity of the participants using a VAS of 0 to 100 mm, where 0 represented no symptoms and 100 represented severe symptoms. Physicians were asked to mark the line corresponding to their assessment and the distance from the left edge was measured. A negative value in change from Baseline indicates an improvement.

  • Physician Global Assessment of Disease Activity During the Open Treatment Period [ Time Frame: Baseline, Weeks 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Physicians were asked to assess disease activity of the participants using a VAS of 0 to 100 mm, where 0 represented no symptoms and 100 represented severe symptoms. Physicians were asked to mark the line corresponding to their assessment and the distance from the left edge was measured. A negative value in change from Baseline indicates an improvement.

  • Patient Global Assessment of Pain During the Double-Blind Treatment Period [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
    Participants were asked to rate their assessment of pain using a VAS of 0 to 100 mm, where 0 represented no pain and 100 represented intolerable pain. Participants were asked to mark the line corresponding to their assessment and the distance from the left edge was measured. A negative value in change from Baseline indicates an improvement.

  • Patient Global Assessment of Pain During the Open Treatment Period [ Time Frame: Baseline and Weeks 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Participants were asked to rate their assessment of pain using a VAS of 0 to 100 mm, where 0 represented no pain and 100 represented intolerable pain. Participants were asked to mark the line corresponding to their assessment and the distance from the left edge was measured. A negative value in change from Baseline indicates an improvement.

  • Synovitis Score During the Double-Blind Treatment Period Assessed Using B-Mode Ultrasound [ Time Frame: Baseline, Weeks 1 and 4 ] [ Designated as safety issue: No ]
    Synovitis was assessed by ultrasonography (B-mode ultrasound and Power Doppler) and scored from "0" to "3", for each of 40 joints (5 metacarpal phalangeal [MCP; left and right] joints, 5 proximal interphalangeal [PIP; left and right] joints, left and right wrists, elbows, shoulders, knees, and ankles, and 5 metatarsal phalangeal [MTP; left and right] joints); synovitis scores were calculated by adding the sum of scores for each joint for a total score ranging from 0 to 120. A score of 0 indicated no damage and a score of 120 indicated most severe damage. Baseline = Last available value before Day 0 (screening or Day 0) for participants with first tocilizumab infusion at Day 0 and last value available before Week 4 (Week 1 or Week 4) for participants with first tocilizumab infusion at Week 4. A negative change from baseline indicated improvement.

  • Synovitis Score During the Double-Blind Treatment Period Assessed Using Power Doppler Ultrasound [ Time Frame: Baseline, Weeks 1 and 4 ] [ Designated as safety issue: No ]
    Synovitis was assessed by ultrasonography (B-mode ultrasound and Power Doppler) and scored from "0" to "3", for each of 40 joints (5 MCP [left and right] joints, 5 PIP [left and right] joints, left and right wrists, elbows, shoulders, knees, and ankles, and 5 MTP [left and right] joints); synovitis scores were calculated by adding the sum of scores for each joint for a total score ranging from 0 to 120 (higher score=more severe disease). Baseline = Last available value before Day 0 (screening or Day 0) for participants with first tocilizumab infusion at Day 0 and last value available before Week 4 (Week 1 or Week 4) for participants with first tocilizumab infusion at Week 4. Negative change from baseline indicated improvement.

  • Percent Change From Baseline in Synovitis Score During the Open Treatment Period Assessed Using B-Mode Ultrasound [ Time Frame: Weeks 12, 24, and 48 ] [ Designated as safety issue: No ]
    Synovitis was assessed by ultrasonography (B-mode ultrasound and Power Doppler) and scored from "0" to "3", for each of 40 joints (5 MCP [left and right] joints, 5 PIP [left and right] joints, left and right wrists, elbows, shoulders, knees, and ankles, and 5 MTP [left and right] joints); synovitis scores were calculated by adding the sum of scores for each joint for a total score ranging from 0 to 120 (higher score=more severe disease). Baseline = Last available value before Day 0 (screening or Day 0) for participants with first tocilizumab infusion at Day 0 and last value available before Week 4 (Week 1 or Week 4) for participants with first tocilizumab infusion at Week 4. Relative change was the percentage (%) change from baseline.

  • Percent Change From Baseline in Synovitis Score During the Open Treatment Period Assessed Using Power Doppler Ultrasound [ Time Frame: Weeks 12, 24, and 48 ] [ Designated as safety issue: No ]
    Synovitis was assessed by ultrasonography (B-mode ultrasound and Power Doppler) and scored from "0" to "3", for each of 40 joints (5 MCP [left and right] joints, 5 PIP [left and right] joints, left and right wrists, elbows, shoulders, knees, and ankles, and 5 MTP [left and right] joints); synovitis scores were calculated by adding the sum of scores for each joint for a total score ranging from 0 to 120 (higher score=more severe disease). Baseline = Last available value before Day 0 (screening or Day 0) for participants with first tocilizumab infusion at Day 0 and last value available before Week 4 (Week 1 or Week 4) for participants with first tocilizumab infusion at Week 4. Relative change was the percentage change from baseline.

  • Erythrocyte Sedimentation Rate During the Double-Blind Treatment Period [ Time Frame: Baseline, Weeks 1 and 4 ] [ Designated as safety issue: No ]
    Erythrocyte sedimentation rate is a biological marker of inflammation, measured in mm per hour (mm/hr). A reduction in ESR indicates improvement.

  • Percent Change From Baseline in Erythrocyte Sedimentation Rate During the Double-Blind Treatment [ Time Frame: Weeks 1 and 4 ] [ Designated as safety issue: No ]
    Erythrocyte sedimentation rate is a biological marker of inflammation. A negative change indicates improvement.

  • Erythrocyte Sedimentation Rate During the Open Treatment Period [ Time Frame: Baseline, Weeks 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Erythrocyte sedimentation rate is a biological marker of inflammation, measured in mm/hr. A reduction in ESR indicates improvement. Baseline = Last available value before Day 0 (screening or Day 0) for participants with first tocilizumab infusion at Day 0 and last value available before Week 4 (Week 1 or Week 4) for participants with first tocilizumab infusion at Week 4.

  • C-Reactive Protein During the Double-Blind Treatment Period [ Time Frame: Baseline, Weeks 1 and 4 ] [ Designated as safety issue: No ]
    C-Reactive protein (CRP) is a biological marker of inflammation and is measured in nanograms per milliliter (ng/mL). A reduction in CRP indicates improvement.

  • Percent Change From Baseline in C-Reactive Protein During the Double-Blind Treatment Period [ Time Frame: Weeks 1 and 4 ] [ Designated as safety issue: No ]
    C-Reactive protein (CRP) is a biological marker of inflammation. Negative changes from baseline indicate improvement.

  • C- Reactive Protein During the Open Treatment Period [ Time Frame: Baseline, Weeks 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    C-reactive protein is a biological marker of inflammation and is measured in nanograms per milliliter (ng/mL). Baseline = Last available value before Day 0 (screening or Day 0) for participants with first tocilizumab infusion at Day 0 and last value available before Week 4 (Week 1 or Week 4) for participants with first tocilizumab infusion at Week 4.

  • Serum Amyloid A Component During the Double-Blind Treatment Period [ Time Frame: Baseline, Weeks 1 and 4 ] [ Designated as safety issue: No ]
    Serum Amyloid A (SAA) component is a biological marker of inflammation and is measured in mg/L. A reduction in SAA indicates improvement.

  • Percent Change From Baseline in Serum Amyloid A Component During the Double-Blind Treatment Period [ Time Frame: Weeks 1 and 4 ] [ Designated as safety issue: No ]
    Serum Amyloid A (SAA) component is a biological marker of inflammation. A negative change from baseline indicates improvement.

  • Serum Amyloid A Component During the Open Treatment Period [ Time Frame: Baseline, Weeks 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Serum Amyloid A (SAA) component is a biological marker of inflammation measured in mg/L. Baseline = Last available value before Day 0 (screening or Day 0) for participants with first tocilizumab infusion at Day 0 and last value available before Week 4 (Week 1 or Week 4) for participants with first tocilizumab infusion at Week 4.

  • Beta 2 Microglobulin Levels During the Open Treatment Period [ Time Frame: Baseline, Weeks 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Beta 2 Microglobulin is a biological marker of inflammation measured in micrograms per milliliter (mcg/mL). Baseline = Last available value before Day 0 (screening or Day 0) for participants with first tocilizumab infusion at Day 0 and last value available before Week 4 (Week 1 or Week 4) for participants with first tocilizumab infusion at Week 4.

  • Beta 2 Microglobulin Levels During the Double-Blind Treatment Period [ Time Frame: Baseline, Weeks 1 and 4 ] [ Designated as safety issue: No ]
    Beta 2 Microglobulin is a biological marker of inflammation measured in micrograms per milliliter (mcg/mL).

  • Percent Change From Baseline in Beta 2 Microglobulin Levels During the Double-Blind Treatment Period [ Time Frame: Weeks 1 and 4 ] [ Designated as safety issue: No ]
    Beta 2 Microglobulin is a biological marker of inflammation. If baseline value was equal to 0, it was replaced by 0.1 to calculate the change from baseline.

  • Bone Mineral Density [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
    To describe bone mineral density (BMD), standardized values were calculated for lumbar spine, hip, femoral neck, and trochanter, taking into account the type of Dual energy X ray absorptiometry (DXA) used. All DXA at baseline were taken into account (done from before screening to Week 8). DXA at end of study were taken into account if they were done after at least 6 infusions of tocilizumab. Values were measured in milligrams per square centimeter (mg/cm^2).

  • Percentage of Participants Treated With Corticosteroids Over the 1-Year Tocilizumab Period [ Time Frame: Baseline, Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 ] [ Designated as safety issue: No ]
  • S-Sclerostin and P-Dkk1 (Wnt Signaling Inhibitor Dickkopf) Over the 1-Year Tocilizumab Period [ Time Frame: Baseline, Weeks 12, 24, and 48 ] [ Designated as safety issue: No ]
    S-Sclerostin and P-Dkk1 are biological markers of bone and cartilage metabolism measured as picograms/milliliter (pg/mL). Baseline is the closest value plus or minus (+/-) 1 month around the first tocilizumab infusion. If values before and after the first infusion were eligible, the value before was taken into account.

  • Serum Procollagen Type II N-Propeptide (s-PIINP), Serum Procollagen Type I N Propeptide (s-PINP), and Serum Carboxy-Terminal Collagen Crosslinks-1 (s-CTX-I) Over the 1-Year Tocilizumab Period [ Time Frame: Baseline and Weeks 12, 24, and 48 ] [ Designated as safety issue: No ]
    S-PIIINP, S-CTX-I, and S-PINP are biological markers of bone and cartilage metabolism. Baseline is the closest value +/- 1 month around the first tocilizumab infusion. If values before and after the first infusion were eligible, the value before was taken into account.

  • Serum Osteogenic Growth Peptide (s-OGP) Over the 1-Year Tocilizumab Period [ Time Frame: Baseline and Weeks 12 and 48 ] [ Designated as safety issue: No ]
    S-OGP is a biological marker of bone and cartilage metabolism measured as picomoles per liter (pmol/L). Baseline is the closest value +/- 1 month around the first tocilizumab infusion. If values before and after the first infusion were eligible, the value before was taken into account.

  • Weekly Methotrexate (MTX) Dose [ Time Frame: Baseline and Weeks 24 and 48 ] [ Designated as safety issue: No ]
    Before entering the study, participants had to be treated with MTX for at least 12 weeks and at a stable dose for at least 8 weeks before the screening visit (10-25 mg per week [mg/week] of oral or parenteral MTX). During the study, treatment with MTX had to be stable during the first month and then could be continued or modified, at the investigator's discretion.

  • HAQ-DI During the Double-Blind Treatment Period [ Time Frame: Screening and Week 4 ] [ 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.

  • HAQ-DI During the Open Treatment Period [ Time Frame: Baseline and Weeks 12, 24, 36, and 48 ] [ 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.

  • Functional Assessment of Chronic Illness in Therapy - Fatigue (FACIT-F) During the Double-Blind Treatment Period [ Time Frame: Day 0, Week 1, and Week 4 ] [ Designated as safety issue: No ]
    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 patient's 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-F score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the participant's health status. Baseline = Last available value before Day 0 (screening or Day 0) for participants with first tocilizumab infusion at Day 0 and last value available before Week 4 (Week 1 or Week 4) for participants with first tocilizumab infusion at Week 4.

  • Percent Change From Baseline in FACIT-F During the Double-Blind Treatment Period [ Time Frame: Week 1 and Week 4 ] [ Designated as safety issue: No ]
    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 patient's 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-F score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the participant's health status. Baseline = Last available value before Day 0 (screening or Day 0) for participants with first tocilizumab infusion at Day 0 and last value available before Week 4 (Week 1 or Week 4) for participants with first tocilizumab infusion at Week 4.

  • FACIT-F During the Open Treatment Period [ Time Frame: Baseline, Weeks 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    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 patient's 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-F score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the participant's health status. Baseline = Last available value before Day 0 (screening or Day 0) for participants with first tocilizumab infusion at Day 0 and last value available before Week 4 (Week 1 or Week 4) for participants with first tocilizumab infusion at Week 4.

  • Hemoglobin Concentration During the Double-Blind Treatment Period [ Time Frame: Baseline and Weeks 1 and 4 ] [ Designated as safety issue: No ]
    Hemoglobin concentrations were determined at each visit to evaluate anemia in participants and measured as grams per deciliter (g/dL).

  • Hemoglobin Concentration During the Open Treatment Period [ Time Frame: Baseline, Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 ] [ Designated as safety issue: No ]
    Hemoglobin concentrations were determined at each visit to evaluate anemia in participants and measured as g/dL.

  • Tender Joint Count (TJC) Based on 28-Joint Count During the Double-Blind Treatment Period [ Time Frame: Baseline and Weeks 1 and 4 ] [ Designated as safety issue: No ]
    Twenty-eight joints were assessed for tenderness. Joints were classified as tender (1)/not tender (0) giving a total possible TJC score of 0 to 28. Baseline = value at Day 0 if available, value at screening otherwise.

  • Percent Change From Baseline in TJC Based on 28-Joint Count During the Double-Blind Treatment Period [ Time Frame: Weeks 1 and 4 ] [ Designated as safety issue: No ]
    Twenty-eight joints were assessed for tenderness. Joints were classified as tender (1)/not tender (0) giving a total possible TJC score of 0 to 28.

  • TJC Based on 28-Joint Count During the Open Treatment Period [ Time Frame: Baseline and Weeks 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Twenty-eight joints were assessed for tenderness and joints were classified as tender (1)/not tender (0), giving a total possible tender joint count score of 0 to 28. Baseline = Last value available before Day 0 (selection or Day 0) for placebo and last value available before Week 4 (Week 1 or Week 4) for tocilizumab group.

  • TJC Based on 40-Joint Count During the Double-Blind Treatment Period [ Time Frame: Baseline and Weeks 1 and 4 ] [ Designated as safety issue: No ]
    Forty joints were assessed for tenderness (5 MCP [left and right] joints, 5 PIP [left and right joints], left and right wrists, elbows, shoulders, knees, and ankles, and 5 MTP [left and right] joints). Joints were classified as tender (1)/not tender (0) giving a total possible TJC score of 0 to 40. Baseline = value at Day 0 if available, value at screening otherwise.

  • Percent Change From Baseline in TJC Based on 40-Joint Count During the Double-Blind Treatment Period [ Time Frame: Weeks 1 and 4 ] [ Designated as safety issue: No ]
    Forty joints were assessed for tenderness (5 MCP [left and right] joints, 5 PIP [left and right joints], left and right wrists, elbows, shoulders, knees, and ankles, and 5 MTP [left and right] joints). Joints were classified as tender (1)/not tender (0) giving a total possible TJC score of 0 to 40.

  • TJC Based on 40-Joint Count During the Open Treatment Period [ Time Frame: Baseline and Weeks 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Forty joints were assessed for tenderness (5 MCP [left and right] joints, 5 PIP [left and right joints], left and right wrists, elbows, shoulders, knees, and ankles, and 5 MTP [left and right] joints). Joints were classified as tender (1)/not tender (0) giving a total possible TJC score of 0 to 40. Baseline = Last value available before Day 0 (selection or Day 0) for placebo and last value available before Week 4 (Week 1 or Week 4) for tocilizumab group.

  • Swollen Joint Count (SJC) Based on 28-Joint Count During the Double-Blind Treatment Period [ Time Frame: Baseline and Weeks 1 and 4 ] [ Designated as safety issue: No ]
    Twenty-eight joints were assessed for swelling. Joints were classified as swollen (1)/not swollen (0) giving a total possible SJC score of 0 to 28. Baseline = value at Day 0 if available, value at screening otherwise.

  • Percent Change From Baseline in SJC Based on 28-Joint Count During the Double-Blind Treatment Period [ Time Frame: Weeks 1 and 4 ] [ Designated as safety issue: No ]
    Twenty-eight joints were assessed for swelling. Joints were classified as swollen (1)/not swollen (0) giving a total possible SJC score of 0 to 28.

  • Swollen Joint Count (SJC) Based on 28-Joint Count During the Open Treatment Period [ Time Frame: Baseline and Weeks 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Twenty-eight joints were assessed for swelling (5 MCP [left and right] joints, 5 PIP [left and right joints], left and right wrists, elbows, shoulders, knees, and ankles, and 5 MTP [left and right] joints) . Joints were classified as swollen (1)/not swollen (0) giving a total possible SJC score of 0 to 28. Baseline = Last value available before Day 0 (selection or Day 0) for placebo and last value available before Week 4 (Week 1 or Week 4) for tocilizumab group.

  • SJC Based on 40-Joint Count During the Double-Blind Treatment Period [ Time Frame: Baseline and Weeks 1 and 4 ] [ Designated as safety issue: No ]
    Forty joints were assessed for swelling (5 MCP [left and right] joints, 5 PIP [left and right joints], left and right wrists, elbows, shoulders, knees, and ankles, and 5 MTP [left and right] joints). Joints were classified as swollen (1)/not swollen (0) giving a total possible SJC score of 0 to 40. Baseline = value at Day 0 if available, value at screening otherwise.

  • Percent Change From Baseline in SJC Based on 40-Joint Count During the Double-Blind Treatment Period [ Time Frame: Weeks 1 and 4 ] [ Designated as safety issue: No ]
    Forty joints were assessed for swelling (5 MCP [left and right] joints, 5 PIP [left and right joints], left and right wrists, elbows, shoulders, knees, and ankles, and 5 MTP [left and right] joints). Joints were classified as swollen (1)/not swollen (0) giving a total possible SJC score of 0 to 40.

  • SJC Based on 40-Joint Count During the Open Treatment Period [ Time Frame: Baseline and Weeks 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Forty joints were assessed for swelling (5 MCP [left and right] joints, 5 PIP [left and right joints], left and right wrists, elbows, shoulders, knees, and ankles, and 5 MTP [left and right] joints). Joints were classified as swollen (1)/not swollen (0) for a total possible score of 0 to 40. Baseline = Last value available before Day 0 (selection or Day 0) for placebo and last value available before Week 4 (Week 1 or Week 4) for tocilizumab group.

  • Disease Activity Score Based on 28-Joints Count (DAS28) During the Double-Blind Treatment Period [ Time Frame: Baseline and Weeks 1 and 4 ] [ Designated as safety issue: No ]
    DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. DAS28 less than or equal to (≤3.2) = low disease activity, DAS28 greater than (>)3.2 to 5.1 = moderate to high disease activity.

  • DAS28 During the Open Treatment Period [ Time Frame: Baseline and Weeks 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. DAS28 less than or equal to (≤3.2) = low disease activity, DAS28 greater than (>)3.2 to 5.1 = moderate to high disease activity.

  • Disease Activity Score Based on 40-Joints Count (DAS40) During the Double-Blind Treatment Period [ Time Frame: Baseline and Weeks 1 and 4 ] [ Designated as safety issue: No ]
    DAS40 calculated from the number of swollen joints and tender joints using the 40-joint count, the erythrocyte sedimentation rate and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity.

  • DAS40 During the Open Treatment Period [ Time Frame: Baseline and Weeks 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    DAS40 was calculated from the number of swollen joints and tender joints using the 40-joint count, the erythrocyte sedimentation rate, and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS40 score ranged from 0 to 10, where higher scores correspond to greater disease activity.


Enrollment: 103
Study Start Date: June 2009
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: tocilizumab [RoActemra/Actemra]
single iv infusion 8 mg/kg
Placebo Comparator: 2 Drug: placebo
single iv infusion
Experimental: 3 Drug: tocilizumab [RoActemra/Actemra]
iv infusion 8mg/kg every 4 weeks for 11 months

  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
  • active moderate or severe rheumatoid arthritis of <10 years duration with inadequate response to methotrexate or anti-TNF
  • on methotrexate treatment for at least 10 weeks, at least 8 weeks on stable dose
  • patients receiving oral corticosteroids and/or NSAIDs should be at stable dose for 4 weeks

Exclusion Criteria:

  • rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA
  • functional class IV by ACR classification
  • history of inflammatory joint disease other than RA
  • previous treatment with cell-depleting therapies, abatacept or rituximab
  • active current or history of recurrent infection, or any major episode of infection requiring hospitalization or treatment with iv antibiotics <4 weeks or oral antibiotics <2 weeks prior to screening
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00977106

Locations
France
Amiens, France, 80094
Amiens, France, 80054
Bayonne, France, 64109
Bois Guillaume, France, 76233
Bordeaux, France, 33076
Brest, France, 29609
Cahors, France, 46005
Chambray Les Tours, France, 37171
Clermont-ferrand, France, 63003
Echirolles, France, 38434
La Roche Sur Yon, France, 85925
Limoges, France, 87042
Lyon, France, 69437
Metz, France, 57077
Nantes, France, 44035
Orleans, France, 45000
Paris, France, 75679
Paris, France, 75877
Paris, France, 75651
Rennes, France, 35203
St Priest En Jarez, France, 42277
Toulouse, France, 31059
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: NCT00977106     History of Changes
Other Study ID Numbers: ML22017, 2008-008309-23
Study First Received: August 18, 2009
Results First Received: June 26, 2014
Last Updated: September 15, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

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 October 19, 2014