Back to resultsA Study of RoActemra/Actemra (Tocilizumab) in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to DMARDs (REMISSION)
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 3
Locations
Morocco
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 active rheumatoid arthritis (DAS28 > 3.2 at screening)
- Inadequate response to DMARDs
- 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 enrollment
- Rheumatic autoimmune disease other than RA
- American College of Rheumatology (ACR) functional class IV
- Prior history of or current inflammatory joint disease other than RA
- Previous treatment with any biologic drug that is used in the treatment of RA
- Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline
- Pregnant or lactating women
- Active current or history of recurrent infection, active TB within the previous 3 years, HIV infection
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
Percentage of participants with adverse events (AEs), serious adverse events (SAEs), severe AEs, AEs leading to withdrawal, AEs leading to death, and treatment-related AEs.
Secondary Outcome Measures
Percentage of Participants With All-Cause Discontinuation of Tocilizumab by Study Visit
Percentage of participants discontinuing study treatment for any reason at every visit; causes of discontinuation in the summary included AEs, deaths, lost to follo-wup, AE and investigator decision and 'not determined'.
Change From Baseline in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) to Highest Value
The difference between baseline and highest values until Week 24 of ALT and AST. The values are measures as international units per liter (UI/L). The change was calculated as the value (highest) at a later timepoint up to Week 24, minus the value at Baseline.
Change From Baseline Low-Density Lipoprotein (LDL) and Total Cholesterol (TC) to Highest Values
Levels of LDL and TC were measured in milligrams/deciliter (mg/dL). Change in LDL and TC were calculated as the value (highest) through Week 24, minus the value at Baseline.
Percentage of Participants With Lipid Elevations by Study Visit
Lipid panel assessed included TC, triglycerides, high-density lipoprotein (HDL), and LDL. Elevations were categorized as follows: LDL cholesterol: Optimal equals (=) less than (<)100 mg/dL, Near optimal=100-129 mg/dL, Borderline high 130-159 mg/dL, High 160-189 mg/dL, Very High ≥190 mg/dL; Total cholesterol: Desirable <200 mg/dL, Borderline high 200-239 mg/dL, High ≥240 mg/dL; HDL cholesterol: Low <40 mg/dL, High ≥60 mg/dL; Triglycerides: Normal <150 mg/dL, Borderline high 150-199 mg/dL, High 200-499 mg/dL, and Very high ≥500 mg/dL.
Disease Activity Score Based on 28-Joint Count (DAS28)
DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate (ESR; in millimeters per hour [mm/hour]) and global health assessment (participant-rated global assessment of disease activity using 10-mm visual analog assessment [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 less than or equal to (≤) 5.1=moderate to high disease activity; DAS28 >5.1=high disease activity.
Percentage of Participants by DAS28 Response Category
DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) 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 ≤3.2 =low disease activity, DAS28 >3.2 to ≤5.1=moderate to high disease activity; DAS28 >5.1=high disease activity.
Percentage of Participants With a Clinically Meaningful Improvement in Disease Activity
DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) 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. A reduction in DAS28 of at least 1.2 units was considered a clinically meaningful improvement.
Time to Achieve Clinically Meaningful Reduction in DAS28
A clinically meaningful improvement in DAS28 was defined as a reduction of at least 1.2 units. Time to achieving clinically meanigful improvement was calculated as the number of days from the first infusion to the first achievement of reduction of 1.2 units in DAS28.
Percentage of Participants Achieving Remission (DAS28 <2.6)
DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) 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 with a DAS28 score <2.6 were considered to have achieved remission.
Percentage of Participants With a Response Assessed Using American College of Rheumatology (ACR) Criteria
The ACR response rates ACR20, ACR50, ACR70 are defined as ≥20%, ≥50%, ≥70% improvement, respectively, in: swollen joint count (SJC) (66 joints) and tender joint count (TJC) (68 joints) and 3 of the following 5 assessments: Patient assessment of pain (VAS); Patient global assessment of disease activity (VAS); Investigator global assessment of disease activity (VAS); and acute phase response (ESR or CRP)
Swollen and Tender Joint Counts
The following 28 joints were assessed by the physician for swelling: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). The following 28 joints were assessed by the physician for tenderness : metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). The change in SJC and TJC was determined as the difference in values from baseline at each visit.
Health Assessment Questionnaire (HAQ)
HAQ was used to assess the physical ability and functional status of participants as well as quality of life. The disability dimension consists of 20 multiple-choice items concerning difficulty in performing 8 common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Participants choose from 4 response categories, ranging from 'without any difficulty' (Score=0) to 'unable to do' (Score=3). The change in HAQ was determined as the difference in values from baseline at each visit.
Patient Global Assessment of Disease Activity (VAS)
The participant's overall assessment of their current disease activity was displayed on a 100-mm horizontal VAS. The left-hand extreme (0 mm) of the line was described as "no disease activity" (symptom free and no arthritis symptoms) and the right-hand extreme (100 mm) was described as "maximum disease activity" (maximum arthritis disease activity). The change in Patient Global Assessment of Disease Activity was determined as the difference in values from baseline at each visit.
Physician's Global Assessment of Disease Activity (VAS)
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 (0 mm) was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme (100 mm) was described as "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 change in Physician's Global Assessment of Disease Activity was determined as the difference in values from baseline at each visit.
Patient Assessment of of Pain (VAS)
The participant's assessment of their current level of pain was displayed on a 100-mm horizontal VAS. The left-hand extreme (0 mm) of the line was described as "no pain" and the right-hand extreme of the line (100 mm) was described as "unbearable pain". The change in participant's perception of pain was determined as the difference in values from baseline at each visit.
C-Reactive Protein (CRP)
CRP is an acute phase inflammatory marker. Levels of CRP increase with inflammation. The change in CRP was determined as the difference in values from baseline and at each visit.
Erythrocyte Sedimentation Rate (ESR)
ESR indirectly measures how much inflammation is in the body. A higher ESR is indicative of increased inflammation. The change in ESR was determined as the difference in values from baseline at each visit.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01610791
Brief Title
A Study of RoActemra/Actemra (Tocilizumab) in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to DMARDs (REMISSION)
Official Title
A Single Arm, Open Label Study to Assess the Safety, Tolerability and Efficacy of Tocilizumab in Active Rheumatoid Arthritis Patients With Inadequate Response to the DMARDs (REMISSION Study)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
March 2010 (undefined)
Primary Completion Date
August 2011 (Actual)
Study Completion Date
August 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 assess the safety and efficacy of RoActemra/Actemra (tocilizumab) in patients with moderate to severe active rheumatoid arthritis who have an inadequate response to disease-modifying antirheumatic drugs (DMARDs). Patients will receive RoActemra/Actemra at a dose of 8 mg/kg intravenously every 4 weeks for 24 weeks (6 infusions).
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
121 (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 iv every 4 weeks, total of 6 infusions
Primary Outcome Measure Information:
Title
Percentage of Participants With Adverse Events
Description
Percentage of participants with adverse events (AEs), serious adverse events (SAEs), severe AEs, AEs leading to withdrawal, AEs leading to death, and treatment-related AEs.
Time Frame
Baseline, Weeks 4, 8, 12, 16, 20, and 24
Secondary Outcome Measure Information:
Title
Percentage of Participants With All-Cause Discontinuation of Tocilizumab by Study Visit
Description
Percentage of participants discontinuing study treatment for any reason at every visit; causes of discontinuation in the summary included AEs, deaths, lost to follo-wup, AE and investigator decision and 'not determined'.
Time Frame
Weeks 4, 8, 12, 16, 20, and 24
Title
Change From Baseline in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) to Highest Value
Description
The difference between baseline and highest values until Week 24 of ALT and AST. The values are measures as international units per liter (UI/L). The change was calculated as the value (highest) at a later timepoint up to Week 24, minus the value at Baseline.
Time Frame
Baseline through Week 24
Title
Change From Baseline Low-Density Lipoprotein (LDL) and Total Cholesterol (TC) to Highest Values
Description
Levels of LDL and TC were measured in milligrams/deciliter (mg/dL). Change in LDL and TC were calculated as the value (highest) through Week 24, minus the value at Baseline.
Time Frame
Baseline through Week 24
Title
Percentage of Participants With Lipid Elevations by Study Visit
Description
Lipid panel assessed included TC, triglycerides, high-density lipoprotein (HDL), and LDL. Elevations were categorized as follows: LDL cholesterol: Optimal equals (=) less than (<)100 mg/dL, Near optimal=100-129 mg/dL, Borderline high 130-159 mg/dL, High 160-189 mg/dL, Very High ≥190 mg/dL; Total cholesterol: Desirable <200 mg/dL, Borderline high 200-239 mg/dL, High ≥240 mg/dL; HDL cholesterol: Low <40 mg/dL, High ≥60 mg/dL; Triglycerides: Normal <150 mg/dL, Borderline high 150-199 mg/dL, High 200-499 mg/dL, and Very high ≥500 mg/dL.
Time Frame
Baseline, Weeks 4, 8, 12, 16, 20, and 24
Title
Disease Activity Score Based on 28-Joint Count (DAS28)
Description
DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate (ESR; in millimeters per hour [mm/hour]) and global health assessment (participant-rated global assessment of disease activity using 10-mm visual analog assessment [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 less than or equal to (≤) 5.1=moderate to high disease activity; DAS28 >5.1=high disease activity.
Time Frame
Baseline, Weeks 4, 8, 12, 16, 20, and 24
Title
Percentage of Participants by DAS28 Response Category
Description
DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) 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 ≤3.2 =low disease activity, DAS28 >3.2 to ≤5.1=moderate to high disease activity; DAS28 >5.1=high disease activity.
Time Frame
Baseline, Weeks 4, 8, 12, 16, 20, and 24
Title
Percentage of Participants With a Clinically Meaningful Improvement in Disease Activity
Description
DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) 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. A reduction in DAS28 of at least 1.2 units was considered a clinically meaningful improvement.
Time Frame
Baseline, Weeks 4, 8, 12, 16, 20, and 24
Title
Time to Achieve Clinically Meaningful Reduction in DAS28
Description
A clinically meaningful improvement in DAS28 was defined as a reduction of at least 1.2 units. Time to achieving clinically meanigful improvement was calculated as the number of days from the first infusion to the first achievement of reduction of 1.2 units in DAS28.
Time Frame
Baseline, Weeks 4, 8, 12, 16, 20, and 24
Title
Percentage of Participants Achieving Remission (DAS28 <2.6)
Description
DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) 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 with a DAS28 score <2.6 were considered to have achieved remission.
Time Frame
Baseline, Weeks 4, 8, 12, 16, 20, and 24
Title
Percentage of Participants With a Response Assessed Using American College of Rheumatology (ACR) Criteria
Description
The ACR response rates ACR20, ACR50, ACR70 are defined as ≥20%, ≥50%, ≥70% improvement, respectively, in: swollen joint count (SJC) (66 joints) and tender joint count (TJC) (68 joints) and 3 of the following 5 assessments: Patient assessment of pain (VAS); Patient global assessment of disease activity (VAS); Investigator global assessment of disease activity (VAS); and acute phase response (ESR or CRP)
Time Frame
Weeks 4, 8, 12, 16, 20, and 24
Title
Swollen and Tender Joint Counts
Description
The following 28 joints were assessed by the physician for swelling: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). The following 28 joints were assessed by the physician for tenderness : metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). The change in SJC and TJC was determined as the difference in values from baseline at each visit.
Time Frame
Baseline, Weeks 4, 8, 12, 16, 20, and 24
Title
Health Assessment Questionnaire (HAQ)
Description
HAQ was used to assess the physical ability and functional status of participants as well as quality of life. The disability dimension consists of 20 multiple-choice items concerning difficulty in performing 8 common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Participants choose from 4 response categories, ranging from 'without any difficulty' (Score=0) to 'unable to do' (Score=3). The change in HAQ was determined as the difference in values from baseline at each visit.
Time Frame
Baseline, Weeks 4, 8, 12, 16, 20, and 24
Title
Patient Global Assessment of Disease Activity (VAS)
Description
The participant's overall assessment of their current disease activity was displayed on a 100-mm horizontal VAS. The left-hand extreme (0 mm) of the line was described as "no disease activity" (symptom free and no arthritis symptoms) and the right-hand extreme (100 mm) was described as "maximum disease activity" (maximum arthritis disease activity). The change in Patient Global Assessment of Disease Activity was determined as the difference in values from baseline at each visit.
Time Frame
Baseline, Weeks 4, 8, 12, 16, 20, and 24
Title
Physician's Global Assessment of Disease Activity (VAS)
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 (0 mm) was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme (100 mm) was described as "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 change in Physician's Global Assessment of Disease Activity was determined as the difference in values from baseline at each visit.
Time Frame
Baseline, Weeks 4, 8, 12, 16, 20, and 24
Title
Patient Assessment of of Pain (VAS)
Description
The participant's assessment of their current level of pain was displayed on a 100-mm horizontal VAS. The left-hand extreme (0 mm) of the line was described as "no pain" and the right-hand extreme of the line (100 mm) was described as "unbearable pain". The change in participant's perception of pain was determined as the difference in values from baseline at each visit.
Time Frame
Baseline, Weeks 4, 8, 12, 16, 20, and 24
Title
C-Reactive Protein (CRP)
Description
CRP is an acute phase inflammatory marker. Levels of CRP increase with inflammation. The change in CRP was determined as the difference in values from baseline and at each visit.
Time Frame
Baseline, Weeks 4, 8, 12, 16, 20, and 24
Title
Erythrocyte Sedimentation Rate (ESR)
Description
ESR indirectly measures how much inflammation is in the body. A higher ESR is indicative of increased inflammation. The change in ESR was determined as the difference in values from baseline at each visit.
Time Frame
Baseline, 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 active rheumatoid arthritis (DAS28 > 3.2 at screening)
Inadequate response to DMARDs
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 enrollment
Rheumatic autoimmune disease other than RA
American College of Rheumatology (ACR) functional class IV
Prior history of or current inflammatory joint disease other than RA
Previous treatment with any biologic drug that is used in the treatment of RA
Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline
Pregnant or lactating women
Active current or history of recurrent infection, active TB within the previous 3 years, HIV infection
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
Casablanca
ZIP/Postal Code
20000
Country
Morocco
City
Fés
ZIP/Postal Code
30000
Country
Morocco
City
Khouribga
ZIP/Postal Code
14000
Country
Morocco
City
Kénitra
ZIP/Postal Code
25000
Country
Morocco
City
Marrakech
ZIP/Postal Code
40000
Country
Morocco
City
Meknés
ZIP/Postal Code
50000
Country
Morocco
City
Rabat
ZIP/Postal Code
10000
Country
Morocco
City
Salé
ZIP/Postal Code
15045
Country
Morocco
12. IPD Sharing Statement
Learn more about this trial
A Study of RoActemra/Actemra (Tocilizumab) in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to DMARDs (REMISSION)
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