Back to resultsA Study of RoActemra/Actemra (Tocilizumab) in Patients With Rheumatoid Arthritis Who Have an Inadequate Response to DMARDs or Anti-TNF
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 3
Locations
Saudi Arabia
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
- Active moderate to severe rheumatoid arthritis of >/= 6 months duration
- >/=1 non-biologic DMARD and/or anti-TNF therapy at stable dose for >/=8 weeks at any time prior to study treatment
- Inadequate clinical response to non-biologic DMARD or anti-TNF therapy
- Oral corticosteroids must be at stable dose for at least 25 out of 28 days prior to first dose of study drug
Exclusion Criteria:
- Pregnant or lactating women
- Major surgery (including joint surgery) within 8 weeks prior to screening or major surgery planned within 6 months of enrolment
- Rheumatic autoimmune disease other than RA
- Functional class IV (ACR classification)
- Prior history of or current joint disease other than RA
- Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline
- Previous treatment with RoActemra/Actemra
- Known active current or history of recurrent infection
- History of or currently active primary or secondary immunodeficiency
- Active tuberculosis requiring treatment within the previous 3 years
- Positive for HIV
Sites / Locations
- King Fahad Specialist Hospital; Oncology
- King Abdulaziz University Hospital
- Heraa General Hospital; Rheumatology
- King Fahad Medical City; Gastroentrology
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single Arm
Arm Description
Outcomes
Primary Outcome Measures
Disease Activity as Measured by Disease Activity Score 28 (DAS28)
The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis (RA). The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (erythrocyte sedimentation rate [ESR] in millimeters per hour [mm/hr]), and general health status (participant global assessment of disease activity using visual analog scale [VAS], range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Number of Participants Who Achieved Remission (DAS28 < 2.6)
The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Time to Das28 Remission
Time to DAS28 Remission was the Time in days from the first infusion of study drug to the achievement of a DAS28 score < 2.6 units. The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Number of Participants Who Achieved a Clinically Meaningful Improvement in DAS28 (Reduction of At Least 1.2 Units)
DAS28 Clinically Significant Improvement was defined as a DAS28 score reduction of at least 1.2 units from Baseline. The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Number of Participants Who Achieved Low Disease Activity (DAS28 < 3.2)
DAS28 low disease activity was defined as a DAS28 score reduction of at least 3.2 units from Baseline. The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Number of Participants Who Achieved Clinically Meaningful Health Assessment Questionnaire Response
Health Assessment Questionnaire (HAQ) is a self-completed participant questionnaire specific for Rheumatoid Arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. To calculate HAQ, the participant must have a domain score for at least 6 out of 8 domains. The HAQ is the sum of the scores, divided by the number of domains that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from baseline indicated improvement. Clinically meaningful HAQ response was defined as an improvement of at least 0.22 units from baseline in the HAQ Disability Index.
Changes in Participant's Fatigue Assessed Using the Mean FACIT-Fatigue Score
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. 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).
Change in Fatigue as Measured Using the Fatigue Visual Analog Scale
The VAS for Fatigue (VAS-F) consists of a 100 mm line, with 0 (No Fatigue) on one end, and 100 (Extreme Fatigue) on the other end, which a participant marks to indicate how much fatigue he or she feels. The marked point in mm is converted into a numeric value from 0 to 100, where 0=no fatigue and 100=maximum fatigue. Increasing numbers=increasing fatigue.
Secondary Outcome Measures
Number of Participants With Any Adverse Event and Serious Adverse Event
An adverse event (AE) is defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event.
Number of Participants With AE or SAE Related Discontinuation of Tocilizumab
It included participants who discontinued from the study due to occurrence of AE or SAE.
Number of Participants Who Achieved ACR20, ACR50, ACR70 and ACR90 Response
ACR20, ACR50, ACR70, and ACR90 are defined as greater than or equal to (≥)20 percent (%), ≥50%, ≥70%, or ≥90% improvement, respectively, in swollen joint count (SJC; 66 joints) and tender joint count (TJC; 68 joints). It also comprises ≥20%, ≥50%, ≥70%, or ≥90% improvement, respectively, in 3 of the following 5 assessments: Patient's Global Assessment of Pain (VAS); Patient's Global Assessment of Disease Activity (VAS); Investigator/Physician's Global Assessment of Disease Activity (VAS); participant's assessment of disability measured by the Health Assessment Questionnaire Disability Index (HAQ-DI); or acute phase reactant (ESR or C-reactive protein [CRP]).
Number of Participants With C-Reactive Protein Abnormality
CRP is a biological marker of inflammation. A reduction in CRP indicates improvement. It is measured in milligram per liter (mg/L).
Number of Participants With Erythrocyte Sedimentation Rate Abnormality
ESR is an acute phase reactant and is a measure of inflammation. It is measured in millimeter per hour (mm/hr).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01326962
Brief Title
A Study of RoActemra/Actemra (Tocilizumab) in Patients With Rheumatoid Arthritis Who Have an Inadequate Response to DMARDs or Anti-TNF
Official Title
Tocilizumab Efficacy and Safety in RA Patients After Inadequate Response to DMARDs or Anti-TNF
Study Type
Interventional
2. Study Status
Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
November 30, 2011 (Actual)
Primary Completion Date
May 12, 2013 (Actual)
Study Completion Date
May 12, 2013 (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 and efficacy of RoActemra/Actemra (tocilizumab) in patients with active, moderate to severe rheumatoid arthritis who have an inadequate response to disease-modifying antirheumatic drugs (DMARDs) or anti-TNF. Patients will receive RoActemra/Actemra at a dose of 8 mg/kg (max 800 mg) intravenously every 4 weeks for a total of 6 infusions. Non-biologic DMARD therapy may be continued throughout the study. Anticipated time on study treatment is 24 weeks.
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
N/A
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single Arm
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
tocilizumab [RoActemra/Actemra]
Intervention Description
8 mg/kg (max. 800 mg) iv every 4 weeks, 6 infusions
Primary Outcome Measure Information:
Title
Disease Activity as Measured by Disease Activity Score 28 (DAS28)
Description
The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis (RA). The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (erythrocyte sedimentation rate [ESR] in millimeters per hour [mm/hr]), and general health status (participant global assessment of disease activity using visual analog scale [VAS], range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Time Frame
Up to 1 year
Title
Number of Participants Who Achieved Remission (DAS28 < 2.6)
Description
The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Time Frame
Up to 1 year
Title
Time to Das28 Remission
Description
Time to DAS28 Remission was the Time in days from the first infusion of study drug to the achievement of a DAS28 score < 2.6 units. The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Time Frame
Up to 1 year
Title
Number of Participants Who Achieved a Clinically Meaningful Improvement in DAS28 (Reduction of At Least 1.2 Units)
Description
DAS28 Clinically Significant Improvement was defined as a DAS28 score reduction of at least 1.2 units from Baseline. The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Time Frame
Up to 1 year
Title
Number of Participants Who Achieved Low Disease Activity (DAS28 < 3.2)
Description
DAS28 low disease activity was defined as a DAS28 score reduction of at least 3.2 units from Baseline. The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Time Frame
Up to 1 year
Title
Number of Participants Who Achieved Clinically Meaningful Health Assessment Questionnaire Response
Description
Health Assessment Questionnaire (HAQ) is a self-completed participant questionnaire specific for Rheumatoid Arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. To calculate HAQ, the participant must have a domain score for at least 6 out of 8 domains. The HAQ is the sum of the scores, divided by the number of domains that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from baseline indicated improvement. Clinically meaningful HAQ response was defined as an improvement of at least 0.22 units from baseline in the HAQ Disability Index.
Time Frame
Up to 1 year
Title
Changes in Participant's Fatigue Assessed Using the Mean FACIT-Fatigue Score
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. 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).
Time Frame
Up to 1 year
Title
Change in Fatigue as Measured Using the Fatigue Visual Analog Scale
Description
The VAS for Fatigue (VAS-F) consists of a 100 mm line, with 0 (No Fatigue) on one end, and 100 (Extreme Fatigue) on the other end, which a participant marks to indicate how much fatigue he or she feels. The marked point in mm is converted into a numeric value from 0 to 100, where 0=no fatigue and 100=maximum fatigue. Increasing numbers=increasing fatigue.
Time Frame
Up to 1 year
Secondary Outcome Measure Information:
Title
Number of Participants With Any Adverse Event and Serious Adverse Event
Description
An adverse event (AE) is defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event.
Time Frame
Up to 1 year
Title
Number of Participants With AE or SAE Related Discontinuation of Tocilizumab
Description
It included participants who discontinued from the study due to occurrence of AE or SAE.
Time Frame
Up to 1 year
Title
Number of Participants Who Achieved ACR20, ACR50, ACR70 and ACR90 Response
Description
ACR20, ACR50, ACR70, and ACR90 are defined as greater than or equal to (≥)20 percent (%), ≥50%, ≥70%, or ≥90% improvement, respectively, in swollen joint count (SJC; 66 joints) and tender joint count (TJC; 68 joints). It also comprises ≥20%, ≥50%, ≥70%, or ≥90% improvement, respectively, in 3 of the following 5 assessments: Patient's Global Assessment of Pain (VAS); Patient's Global Assessment of Disease Activity (VAS); Investigator/Physician's Global Assessment of Disease Activity (VAS); participant's assessment of disability measured by the Health Assessment Questionnaire Disability Index (HAQ-DI); or acute phase reactant (ESR or C-reactive protein [CRP]).
Time Frame
Up to 1 year
Title
Number of Participants With C-Reactive Protein Abnormality
Description
CRP is a biological marker of inflammation. A reduction in CRP indicates improvement. It is measured in milligram per liter (mg/L).
Time Frame
Up to 1 year
Title
Number of Participants With Erythrocyte Sedimentation Rate Abnormality
Description
ESR is an acute phase reactant and is a measure of inflammation. It is measured in millimeter per hour (mm/hr).
Time Frame
Up to 1 year
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
Active moderate to severe rheumatoid arthritis of >/= 6 months duration
>/=1 non-biologic DMARD and/or anti-TNF therapy at stable dose for >/=8 weeks at any time prior to study treatment
Inadequate clinical response to non-biologic DMARD or anti-TNF therapy
Oral corticosteroids must be at stable dose for at least 25 out of 28 days prior to first dose of study drug
Exclusion Criteria:
Pregnant or lactating women
Major surgery (including joint surgery) within 8 weeks prior to screening or major surgery planned within 6 months of enrolment
Rheumatic autoimmune disease other than RA
Functional class IV (ACR classification)
Prior history of or current joint disease other than RA
Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline
Previous treatment with RoActemra/Actemra
Known active current or history of recurrent infection
History of or currently active primary or secondary immunodeficiency
Active tuberculosis requiring treatment within the previous 3 years
Positive for HIV
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
King Fahad Specialist Hospital; Oncology
City
Dammam
ZIP/Postal Code
31444
Country
Saudi Arabia
Facility Name
King Abdulaziz University Hospital
City
Jeddah
ZIP/Postal Code
21589
Country
Saudi Arabia
Facility Name
Heraa General Hospital; Rheumatology
City
Makkah
Country
Saudi Arabia
Facility Name
King Fahad Medical City; Gastroentrology
City
Riyadh
ZIP/Postal Code
11525
Country
Saudi Arabia
12. IPD Sharing Statement
Citations:
PubMed Identifier
27236390
Citation
Abdulkader OAF, Qushmaq K, Aljishi F. Tocilizumab efficacy and safety in rheumatoid arthritis patients after inadequate response to disease-modifying anti-rheumatic drugs oranti-tumor necrosis factor. Ann Saudi Med. 2016 May-Jun;36(3):190-6. doi: 10.5144/0256-4947.2016.190. Erratum In: Ann Saudi Med. 2017 Jul-Aug;37(4):339.
Results Reference
derived
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A Study of RoActemra/Actemra (Tocilizumab) in Patients With Rheumatoid Arthritis Who Have an Inadequate Response to DMARDs or Anti-TNF
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