A Study of Tocilizumab as Monotherapy or in Combination With DMARDs in Patients With Moderate to Severe Active Rheumatoid Arthritis
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
tocilizumab [RoActemra/Actemra]
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
Eligibility Criteria
Inclusion Criteria:
- adult patients, >/=18 years of age
- moderate to severe rheumatoid arthritis (DAS28 >3.2) of 6 months duration
- inadequate clinical response to non-biologic DMARDs or anti-TNF
- bodyweight </=150 kg
Exclusion Criteria:
- rheumatic autoimmune disease or inflammatory joint disease other than RA
- major surgery within 8 weeks prior to screening or planned major surgery within 6 months following screening
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
Outcomes
Primary Outcome Measures
Percentage of Participants Reporting Any Adverse Event - Overall Summary of Events
Percentage of participants with a serious adverse event (SAE), who died, with an adverse event (AE), or study drug related AE during the study.
Secondary Outcome Measures
Percentage of Participants by Disease Activity Score Based on 28-Joint Count (DAS28) Category
DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hr]) and global health assessment (participant rated global assessment of disease activity using 10-mm Visual analog scale - VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. A DAS28 score of greater than (>)5.1 indicated high disease activity, a score of >3.2 but less than or equal to (≤)5.1 indicated moderate disease activity, a score of greater than or equal to (≥)2.6 but ≤3.2 indicated low disease activity, and a score of less than <2.6 indicated disease remission. Week 24 is the Follow-Up visit.
Percentage of Participants Achieving a Clinically Meaningful Improvement as Measured by DAS28
DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hr) 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. Participants achieved a clinically meaningful improvement in DAS28 if there was a reduction of at least 1.2 units from baseline.
Time to DAS28 Response by DAS28 Category
Time to response is the number of days from date of first infusion to date of event. DAS28 response was defined as achievement of Low Disease Activity (DAS28 ≥2.6 to ≤3.2), Remission (DAS28 <2.6), or Clinically Meaningful Improvement (change of >1.2 from baseline).
Percentage of Participants With a Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) of at Least 0.22 Units
HAQ 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=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.
Percentage of Participants With Improvement in Physical Function by HAQ-DI Category
Physical function scoring was as follows with respect to performance of participant's everyday activities: 0=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. The HAQ-DI score at every visit was categorized into none to mild disability (HAQ-DI <1), moderate disability (1≤ HAQ-DI <2) and severe disability (HAQ-DI ≥2). The percentages of the participants falling in each of these categories with respect to the visits were determined.
HAQ-DI Score by Visit
HAQ 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=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..
C-Reactive Protein (CRP) Values by Study Visit
CRP is an acute phase inflammatory marker. The serum concentration of CRP is measured in milligrams per liter (mg/L). A reduction in the level is considered an improvement.
Erythrocyte Sedimentation Rate
ESR (measured in mm/hr) is an inflammation marker used to determine acute phase response.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01089023
Brief Title
A Study of Tocilizumab as Monotherapy or in Combination With DMARDs in Patients With Moderate to Severe Active Rheumatoid Arthritis
Official Title
Multicenter, Open-Label Study to Evaluate the Safety, Tolerability and the Effect on Disease Activity of Tocilizumab in Patients With Active Rheumatoid Arthritis on Background Non-biologic DMARDs Who Have an Inadequate Response to Current Non-biologic DMARD and/or Anti- TNF Therapy.
Study Type
Interventional
2. Study Status
Record Verification Date
June 2014
Overall Recruitment Status
Completed
Study Start Date
January 2010 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
December 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 open-label single-arm study will evaluate the safety, tolerability and efficacy of tocilizumab [RoActemra/Actemra] in patients with moderate to severe rheumatoid arthritis who experience an inadequate clinical response to a stable dose of non-biologic disease modifying anti-rheumatic drugs (DMARD) or anti-tumor necrosis factors (TNFs). RoActemra/Actemra will be administered as a monotherapy or in combination with DMARDs. RoActemra/Actemra will be administered as intravenous infusion at a dose of 8 mg/kg every 4 weeks for a total of 6 infusions. The anticipated time on study treatment is 24 weeks. The target sample size is 50-150 patients.
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 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
95 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
tocilizumab [RoActemra/Actemra]
Intervention Description
8 mg/kg iv infusion, every 4 weeks for a total of 6 infusions
Primary Outcome Measure Information:
Title
Percentage of Participants Reporting Any Adverse Event - Overall Summary of Events
Description
Percentage of participants with a serious adverse event (SAE), who died, with an adverse event (AE), or study drug related AE during the study.
Time Frame
Baseline and Weeks 2, 4, 8, 12, 16, 20, and 24
Secondary Outcome Measure Information:
Title
Percentage of Participants by Disease Activity Score Based on 28-Joint Count (DAS28) Category
Description
DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hr]) and global health assessment (participant rated global assessment of disease activity using 10-mm Visual analog scale - VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. A DAS28 score of greater than (>)5.1 indicated high disease activity, a score of >3.2 but less than or equal to (≤)5.1 indicated moderate disease activity, a score of greater than or equal to (≥)2.6 but ≤3.2 indicated low disease activity, and a score of less than <2.6 indicated disease remission. Week 24 is the Follow-Up visit.
Time Frame
Baseline and Weeks 4, 8, 12, 16, 20, and 24
Title
Percentage of Participants Achieving a Clinically Meaningful Improvement as Measured by DAS28
Description
DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hr) 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. Participants achieved a clinically meaningful improvement in DAS28 if there was a reduction of at least 1.2 units from baseline.
Time Frame
Weeks 4, 8, 12, 16, 20, and 24
Title
Time to DAS28 Response by DAS28 Category
Description
Time to response is the number of days from date of first infusion to date of event. DAS28 response was defined as achievement of Low Disease Activity (DAS28 ≥2.6 to ≤3.2), Remission (DAS28 <2.6), or Clinically Meaningful Improvement (change of >1.2 from baseline).
Time Frame
Weeks 4, 8, 12, 16, 20, and 24
Title
Percentage of Participants With a Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) of at Least 0.22 Units
Description
HAQ 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=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.
Time Frame
Weeks 4, 8, 12, 16, 20, and 24
Title
Percentage of Participants With Improvement in Physical Function by HAQ-DI Category
Description
Physical function scoring was as follows with respect to performance of participant's everyday activities: 0=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. The HAQ-DI score at every visit was categorized into none to mild disability (HAQ-DI <1), moderate disability (1≤ HAQ-DI <2) and severe disability (HAQ-DI ≥2). The percentages of the participants falling in each of these categories with respect to the visits were determined.
Time Frame
Baseline, Weeks 4, 8, 12, 16, 20, and 24
Title
HAQ-DI Score by Visit
Description
HAQ 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=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..
Time Frame
Baseline and Weeks 4, 8, 12, 16, 20, and 24
Title
C-Reactive Protein (CRP) Values by Study Visit
Description
CRP is an acute phase inflammatory marker. The serum concentration of CRP is measured in milligrams per liter (mg/L). A reduction in the level is considered an improvement.
Time Frame
Baseline and Weeks 4, 8, 12, 16, 20, and 24
Title
Erythrocyte Sedimentation Rate
Description
ESR (measured in mm/hr) is an inflammation marker used to determine acute phase response.
Time Frame
Baseline and Weeks 4, 8, 12, 16, 20, and 24
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
moderate to severe rheumatoid arthritis (DAS28 >3.2) of 6 months duration
inadequate clinical response to non-biologic DMARDs or anti-TNF
bodyweight </=150 kg
Exclusion Criteria:
rheumatic autoimmune disease or inflammatory joint disease other than RA
major surgery within 8 weeks prior to screening or planned major surgery within 6 months following screening
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Manama
ZIP/Postal Code
12
Country
Bahrain
City
Riffa
ZIP/Postal Code
28743
Country
Bahrain
City
Isfahan
ZIP/Postal Code
8174675731
Country
Iran, Islamic Republic of
City
Tehran
ZIP/Postal Code
1333631151
Country
Iran, Islamic Republic of
City
Tehran
ZIP/Postal Code
14114
Country
Iran, Islamic Republic of
City
Safat
ZIP/Postal Code
13041
Country
Kuwait
City
Doha
ZIP/Postal Code
3050
Country
Qatar
City
Abu Dhabi
ZIP/Postal Code
51900
Country
United Arab Emirates
City
Abu Dhabi
Country
United Arab Emirates
12. IPD Sharing Statement
Learn more about this trial
A Study of Tocilizumab as Monotherapy or in Combination With DMARDs in Patients With Moderate to Severe Active Rheumatoid Arthritis
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