Back to resultsA Study of RoActemra/Actemra (Tocilizumab) in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Disease-Modifying Antirheumatic Drugs (DMARDs) (ALABASTER)
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 3
Locations
Bosnia and Herzegovina
Study Type
Interventional
Intervention
methotrexate
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 (RA)
- On methotrexate treatment (oral or parenteral) for at least 12 weeks, at stable dose of at least 15 mg/week for at least 6 weeks
- Oral corticosteroids must have been at stable dose of </= 10 mg/day prednisone (or equivalent) for at least 25 out of 28 days prior to first dose of study drug
- Body weight </= 150 kg
Exclusion Criteria:
- Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months of study entry
- Rheumatic autoimmune disease other than RA
- Functional class IV according to American College of Rheumatology (ACR) classification
- Prior history of or current inflammatory joint disease other then RA
- Treatment with traditional DMARDs other than methotrexate within 1 month (for leflunomide 3 months) prior to baseline
- Treatment with any biologic drug that is used in the treatment or RA
- Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline
- Known active current or history of recurrent infection
- History of or currently active primary or secondary immunodeficiency
- Positive for HIV
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single Arm
Arm Description
Outcomes
Primary Outcome Measures
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs of Special Interest (AESIs)
AEs, SAEs and AESI were recorded from the Screening Visit until the final visit at Week 24.
Secondary Outcome Measures
Mean Disease Activity Score Based on 28 Joint Count (DAS28) by Visit
DAS28 was calculated using the 28 joints count, the C-reactive protein levels (CRP) and participant's global assessment (PtGA) of disease activity. The following formula was used to determine DAS28.
DAS28 (equals) = 0.56 × (square root of) √(TJC28) + 0.28 × √(SJC28) + 0.36 × ln(CRP+1) + 0.014 × GH + 0.96 where, TJC28 = tender joint count on 28 joints, SJC28 = swollen joint count on 28 joints, ln = natural log, CRP = C-reactive protein (mg/L), and GH = general health, determined by participant's global assessment of disease activity (100- millimeter [mm] visual analog scale [ VAS]).
The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Percentage of Participants Achieving Low Disease Activity (LDA) and Clinical Remission (CR) as Assessed Using DAS28
DAS28 was calculated using the 28 joints count, the CRP and PtGA of disease activity. The following formula was used to determine DAS28.
DAS28 = 0.56 × √(TJC28) + 0.28 × √(SJC28) + 0.36 × ln(CRP+1) + 0.014 × GH + 0.96 where, TJC28 = tender joint count on 28 joints, SJC28 = swollen joint count on 28 joints, ln = natural log, CRP = C-reactive protein (mg/L), and GH = general health, determined by participant's global assessment of disease activity (100-mm VAS).
The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. Participants were considered to have low disease activity when DAS28 was less than or equal to (≤) 3.2 and in clinical remission when DAS28 scores were less than (<) 2.6
Swollen and Tender Joint Counts
66 and 68 joints were assessed by the physician for tenderness or swelling respectively. The joints were counted as tender/not tender (tender=1; not tender=0) and swollen/not swollen (swollen=1; not swollen=0) and scored. The scores ranged from 0 to 66 for TJC and 0 to 68 for SJC. A negative change from baseline represents an improvement.
Physician's Global Assessment of Disease Activity
Physician's global assessment of disease activity was performed using a 100 mm VAS ranging from no arthritis activity (0) to maximal arthritis activity (100). The distance in mm from the left edge of the scale was measured. Higher scores indicated higher disease activity. A negative change from baseline represents an improvement.
Participant's Global Assessment of Disease Activity
Participant's global assessment of disease activity was performed using a 100 mm VAS ranging from no arthritis activity (0) to maximal arthritis activity (100). The distance in mm from the left edge of the scale was measured. Higher scores indicated higher disease activity. A negative change from baseline represents an improvement.
Participant's Global Assessment of Pain
Participant's global assessment of pain was performed using a 100 mm VAS ranging from no pain (0) at the left edge to unbearable pain (100) at the right edge. The distance in mm from the left edge of the scale was measured. A negative change from baseline represents an improvement.
CRP Levels
CRP is a marker of acute phase inflammation and is measured in mg/L. A negative change from baseline represents an improvement.
Erythrocyte Sedimentation Rate (ESR)
ESR is a marker of inflammation and is measured in millimeters per hour (mm/hour). A negative change from baseline represents an improvement.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01235507
Brief Title
A Study of RoActemra/Actemra (Tocilizumab) in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Disease-Modifying Antirheumatic Drugs (DMARDs) (ALABASTER)
Official Title
Actemra - Local Bosnian Open, Multicentric, Trial to Evaluate Safety, Tolerability and Efficacy of Tocilizumab in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis After Inadequate Response to DMARDs
Study Type
Interventional
2. Study Status
Record Verification Date
November 2014
Overall Recruitment Status
Completed
Study Start Date
February 2011 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
December 2012 (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 assess the safety and efficacy of RoActem ra/Actemra (tocilizumab) in combination with methotrexate in patients with activ e moderate to severe rheumatoid arthritis who have an inadequate response to dis ease-modifying antirheumatic drugs (DMARDs). Patients will receive RoActemra/Act emra at a dose of 8 mg/kg (maximum 800 mg) intravenously every 4 weeks for a tot al of 6 infusions. Methotrexate will be continued at a stable dose. 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
Non-Randomized
Enrollment
71 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single Arm
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
methotrexate
Intervention Description
stable dose as prescribed
Intervention Type
Drug
Intervention Name(s)
tocilizumab [RoActemra/Actemra]
Intervention Description
8 m/kg (maximum 800 mg) intravenously every 4 weeks for a total of 6 infusions
Primary Outcome Measure Information:
Title
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs of Special Interest (AESIs)
Description
AEs, SAEs and AESI were recorded from the Screening Visit until the final visit at Week 24.
Time Frame
Screening Visit, Baseline, Weeks 4, 8, 12, 16, 20 and 24
Secondary Outcome Measure Information:
Title
Mean Disease Activity Score Based on 28 Joint Count (DAS28) by Visit
Description
DAS28 was calculated using the 28 joints count, the C-reactive protein levels (CRP) and participant's global assessment (PtGA) of disease activity. The following formula was used to determine DAS28.
DAS28 (equals) = 0.56 × (square root of) √(TJC28) + 0.28 × √(SJC28) + 0.36 × ln(CRP+1) + 0.014 × GH + 0.96 where, TJC28 = tender joint count on 28 joints, SJC28 = swollen joint count on 28 joints, ln = natural log, CRP = C-reactive protein (mg/L), and GH = general health, determined by participant's global assessment of disease activity (100- millimeter [mm] visual analog scale [ VAS]).
The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Time Frame
Baseline, Weeks 8, 16 and 24
Title
Percentage of Participants Achieving Low Disease Activity (LDA) and Clinical Remission (CR) as Assessed Using DAS28
Description
DAS28 was calculated using the 28 joints count, the CRP and PtGA of disease activity. The following formula was used to determine DAS28.
DAS28 = 0.56 × √(TJC28) + 0.28 × √(SJC28) + 0.36 × ln(CRP+1) + 0.014 × GH + 0.96 where, TJC28 = tender joint count on 28 joints, SJC28 = swollen joint count on 28 joints, ln = natural log, CRP = C-reactive protein (mg/L), and GH = general health, determined by participant's global assessment of disease activity (100-mm VAS).
The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. Participants were considered to have low disease activity when DAS28 was less than or equal to (≤) 3.2 and in clinical remission when DAS28 scores were less than (<) 2.6
Time Frame
Weeks 8, 16 and 24
Title
Swollen and Tender Joint Counts
Description
66 and 68 joints were assessed by the physician for tenderness or swelling respectively. The joints were counted as tender/not tender (tender=1; not tender=0) and swollen/not swollen (swollen=1; not swollen=0) and scored. The scores ranged from 0 to 66 for TJC and 0 to 68 for SJC. A negative change from baseline represents an improvement.
Time Frame
Baseline, Weeks 8, 16 and 24
Title
Physician's Global Assessment of Disease Activity
Description
Physician's global assessment of disease activity was performed using a 100 mm VAS ranging from no arthritis activity (0) to maximal arthritis activity (100). The distance in mm from the left edge of the scale was measured. Higher scores indicated higher disease activity. A negative change from baseline represents an improvement.
Time Frame
Baseline, Weeks 8, 16 and 24
Title
Participant's Global Assessment of Disease Activity
Description
Participant's global assessment of disease activity was performed using a 100 mm VAS ranging from no arthritis activity (0) to maximal arthritis activity (100). The distance in mm from the left edge of the scale was measured. Higher scores indicated higher disease activity. A negative change from baseline represents an improvement.
Time Frame
Baseline, Weeks 8, 16 and 24
Title
Participant's Global Assessment of Pain
Description
Participant's global assessment of pain was performed using a 100 mm VAS ranging from no pain (0) at the left edge to unbearable pain (100) at the right edge. The distance in mm from the left edge of the scale was measured. A negative change from baseline represents an improvement.
Time Frame
Baseline, Weeks 8, 16 and 24
Title
CRP Levels
Description
CRP is a marker of acute phase inflammation and is measured in mg/L. A negative change from baseline represents an improvement.
Time Frame
Baseline, Weeks 8, 16 and 24
Title
Erythrocyte Sedimentation Rate (ESR)
Description
ESR is a marker of inflammation and is measured in millimeters per hour (mm/hour). A negative change from baseline represents an improvement.
Time Frame
Baseline, Weeks 8, 16 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
Active moderate to severe rheumatoid arthritis (RA)
On methotrexate treatment (oral or parenteral) for at least 12 weeks, at stable dose of at least 15 mg/week for at least 6 weeks
Oral corticosteroids must have been at stable dose of </= 10 mg/day prednisone (or equivalent) for at least 25 out of 28 days prior to first dose of study drug
Body weight </= 150 kg
Exclusion Criteria:
Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months of study entry
Rheumatic autoimmune disease other than RA
Functional class IV according to American College of Rheumatology (ACR) classification
Prior history of or current inflammatory joint disease other then RA
Treatment with traditional DMARDs other than methotrexate within 1 month (for leflunomide 3 months) prior to baseline
Treatment with any biologic drug that is used in the treatment or RA
Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline
Known active current or history of recurrent infection
History of or currently active primary or secondary immunodeficiency
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:
City
Banja Luka
ZIP/Postal Code
78 000
Country
Bosnia and Herzegovina
City
Sarajevo
ZIP/Postal Code
71000
Country
Bosnia and Herzegovina
City
Tuzla
ZIP/Postal Code
75000
Country
Bosnia and Herzegovina
12. IPD Sharing Statement
Learn more about this trial
A Study of RoActemra/Actemra (Tocilizumab) in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Disease-Modifying Antirheumatic Drugs (DMARDs) (ALABASTER)
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