Back to resultsA Study in Patients With Moderate to Severe Active Rheumatoid Arthritis Comparing Different Infusion Durations of RoActemra/Actemra (Tocilizumab) Treatment
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Tocilizumab
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
Eligibility Criteria
Inclusion Criteria:
- Adult patients, at least 18 years of age, inclusive
- Diagnosis of rheumatoid arthritis of at least 6 months duration
- Moderate to severe active rheumatoid arthritis (DAS28 >/=3.2)
- Patients received at least 1 disease-modifying anti-rheumatic drug (DMARD) and/or 1 or more TNFalfa-inhibitors over a period of at least 8 weeks
Exclusion Criteria:
- Major surgery (including joint surgery) within 8 weeks prior to screening or planned surgery within 6 months following randomization
- Rheumatic autoimmune disease other than rheumatoid arthritis
- Prior history of or current inflammatory joint disease other than rheumatoid arthritis
- Functional class IV (ACR criteria)
- History of severe allergic reaction to human, humanized or murine monoclonal antibodies
- Known active current or history of recurrent infection (including tuberculosis)
- Primary or secondary immunodeficiency (history of or currently active)
- Body weight >150 kg
- Previous treatment with any cell-depleting therapies
- Previous treatment with tocilizumab
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Tocilizumab, Normal Administration
Tocilizumab, Fast Administration
Arm Description
Tocilizumab 8 mg/kg infusion of 60 minutes duration every 4 weeks for 6 infusions (up to 24 weeks)
Tocilizumab 8 mg/kg infusion of 31 minutes duration every 4 weeks for 6 infusions (up to 24 weeks). The first infusion was 1 hour. If an infusion reaction occurred during any treatment, 1 hour infusions were used for all subsequent infusions
Outcomes
Primary Outcome Measures
Percentage of Participants With Any Infusion Reaction
An infusion reaction was defined as any adverse event (AE) that occurred during the infusion or during the 24 hours following the infusion and deemed possibly or probably related to tocilizumab.
Secondary Outcome Measures
Percentage of Participants Discontinuing Tocilizumab in Response to an AE or a Serious Adverse Event (SAE)
All occurrences of participants who received at least 1 infusion of tocilizumab and then stopped tocilizumab infusions due to an AE or SAE were analyzed.
Percentage of Participants Discontinuing Tocilizumab for Other Reasons
Participants that stopped the administration of tocilizumab and discontinued the study prematurely due to reasons other than an AE or SAE were analyzed.
Percentage of Participants With Increased Liver Enzyme Values of Greater Than (>)1.5 Times, or >3 Times, or >5 Times Over the Upper Limit of Normal (ULN) by Visit Among Participants Who Completed All Visits
Increased liver enzyme values defined as Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) values of >1.5 times, or >3 times, or >5 times over the ULN. Almost none of the participants had increased measurements of AST, thus only values of ALT were presented. None of the participants presented with increased values of ALT above 3 or 5 ULN at any of the visits.
ITT Completers is defined as a subset of the participants in the ITT population who completed all study visits.
Percentage of Participants With Increased Lipid Values by Visit Among Participants Who Completed All Visits
Increased levels of high density lipoproteins (HDL) equal to or greater than (≥)1.5 millimoles per liter (mmol/L), and low density lipoproteins (LDL) ≥4.1 mmol/L, and total cholesterol ≥5.1 mmol/L, are defined according to the Adult Treatment Panel III (ATP-III) guidelines.
Percentage of Participants With a Reduction of at Least 1.2 Points in Disease Activity Score Based on 28-Joint Count (DAS28) by Visit Among Participants Who Completed All Visits
Improvement in Rheumatoid Arthritis (RA) disease activity was measured by the DAS28 score, which is an index combining measurements of swollen and tender joints, acute phase response High sensitivity C-Reactive Protein (hsCRP), and global assessment of disease activity by the participant. A clinically meaningful improvement was defined as a reduction of at least 1.2 units in the DAS28 score during the study period. A low disease activity was defined as a DAS28 score less than (<)3.2, and remission was defined as a DAS28 score <2.6.
Percentage of Participants Achieving a DAS28 Score Below 3.2 (Low Disease Activity) by Visit Among Participants Who Completed All Visits
Improvement in RA disease activity was measured by the DAS28 score, which is an index combining measurements of swollen and tender joints, acute phase response hsCRP, and global assessment of disease activity by the participant. A clinically meaningful improvement was defined as a reduction of at least 1.2 units in the DAS28 score during the study period. A low disease activity was defined as a DAS28 score <3.2, and remission was defined as a DAS28 score <2.6.
Percentage of Participants Achieving a DAS28 Score Below 2.6 (Remission) by Visit Among Participants Who Completed All Visits
Improvement in RA disease activity was measured by the DAS28 score, which is an index combining measurements of swollen and tender joints, acute phase response hsCRP, and global assessment of disease activity by the participant. A clinically meaningful improvement was defined as a reduction of at least 1.2 units in the DAS28 score during the study period. A low disease activity was defined as a DAS28 score <3.2, and remission was defined as a DAS28 score <2.6.
DAS28 Score by Visit Among Participants Who Completed All Visits
Improvement in RA disease activity was measured by the DAS28 score, which is an index combining measurements of swollen and tender joints, acute phase response hsCRP, and global assessment of disease activity by the participant. A clinically meaningful improvement was defined as a reduction of at least 1.2 units in the DAS28 score during the study period. A low disease activity was defined as a DAS28 score <3.2, and remission was defined as a DAS28 score <2.6.
Percentage of Participants Achieving American College of Rheumatology 20 Percent (%) Improvement (ACR20 Response) by Visit Among Participants Who Completed All Visits
ACR20 response is defined as an improvement of ≥20% in swollen joint count (SJC; 66 joints) and tender joint count (TJC; 68 joints) as well as ≥20% improvement in at least 3 of the following 5 remaining ACR assessments: Patient Global Assessment of Pain; Patient Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; Health Assessment Questionnaire - Disability Index (HAQ-DI); and acute phase reactive factors (Erythrocyte Sedimentation Rate [ESR] or C-Reactive Protein [CRP]).
Percentage of Participants Achieving ACR 50% Improvement (ACR50 Response) by Visit Among Participants Who Completed All Visits
ACR50 response is defined as an improvement of ≥50% in SJC (66 joints) and TJC (68 joints) as well as ≥50% improvement in at least 3 of the following 5 remaining ACR assessments: Patient Global Assessment of Pain; Patient Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; HAQ-DI; and acute phase reactive factors (ESR or CRP).
Percentage of Participants Achieving ACR 70% Improvement (ACR70 Response) by Visit, Among Participants Who Completed All Visits
ACR70 response is defined as an improvement of ≥70% in SJC (66 joints) and TJC (68 joints) as well as ≥70% improvement in at least 3 of the following 5 remaining ACR assessments: Patient Global Assessment of Pain; Patient Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; HAQ-DI; and acute phase reactive factors (ESR or CRP).
Percentage of Participants Achieving ACR 90% Improvement (ACR90 Response) by Visit Among Participants Who Completed All Visits
ACR90 response is defined as an improvement of ≥90% in SJC (66 joints) and TJC (68 joints) as well as ≥90% improvement in at least 3 of the following 5 remaining ACR assessments: Patient Global Assessment of Pain; Patient Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; HAQ-DI; and acute phase reactive factors (ESR or CRP).
High Sensitivity C-Reactive Protein (hsCRP) Levels by Visit Among Participants Who Completed All Visits
hsCRP is a marker for inflammation and is measured in milligrams per liter (mg/L). High levels of this protein indicate inflammation in diseases such as RA.
Modified Health Assessment Questionnaire (M-HAQ) Score by Visit Among Participants Who Completed All Visits
M-HAQ is a self-reported, valid assessment of functional disability in RA. Assessment based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. Scores range 0 to 3; without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3.
Percentage of Participants With Improvement of at Least 0.22 Units in M-HAQ Compared to Baseline Per Visit Among Participants Who Completed All Visits
M-HAQ is a self-reported, valid assessment of functional disability in RA. Assessment based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. Scores range 0 to 3; without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01468077
Brief Title
A Study in Patients With Moderate to Severe Active Rheumatoid Arthritis Comparing Different Infusion Durations of RoActemra/Actemra (Tocilizumab) Treatment
Official Title
Multicenter, Randomized, Parallel Group Study to Compare the Incidence of Tocilizumab Related Infusion Reactions in Patients With Moderate to Severe Active RA, When Infusion is Given Over 31 Minutes Compared to 1 Hour
Study Type
Interventional
2. Study Status
Record Verification Date
July 2015
Overall Recruitment Status
Completed
Study Start Date
November 2011 (undefined)
Primary Completion Date
September 2013 (Actual)
Study Completion Date
September 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 multi-center, randomized, parallel-group, active-controlled, open-label study will evaluate the safety and efficacy of a shortened RoActemra/Actemra (tocilizumab) infusion time compared to the normal infusion time. Patients will be randomized to 8 mg/kg RoActemra/Actemra infusion of 31 minutes every 4 weeks or to RoActemra/Actemra 8 mg/kg infusion of 60 minutes every 4 weeks. The 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 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
47 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tocilizumab, Normal Administration
Arm Type
Experimental
Arm Description
Tocilizumab 8 mg/kg infusion of 60 minutes duration every 4 weeks for 6 infusions (up to 24 weeks)
Arm Title
Tocilizumab, Fast Administration
Arm Type
Experimental
Arm Description
Tocilizumab 8 mg/kg infusion of 31 minutes duration every 4 weeks for 6 infusions (up to 24 weeks). The first infusion was 1 hour. If an infusion reaction occurred during any treatment, 1 hour infusions were used for all subsequent infusions
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Other Intervention Name(s)
RoActemra, Actemra
Intervention Description
8 mg/kg infusion
Primary Outcome Measure Information:
Title
Percentage of Participants With Any Infusion Reaction
Description
An infusion reaction was defined as any adverse event (AE) that occurred during the infusion or during the 24 hours following the infusion and deemed possibly or probably related to tocilizumab.
Time Frame
Baseline (Day 1), and Weeks 4, 8, 12, 16, and 20
Secondary Outcome Measure Information:
Title
Percentage of Participants Discontinuing Tocilizumab in Response to an AE or a Serious Adverse Event (SAE)
Description
All occurrences of participants who received at least 1 infusion of tocilizumab and then stopped tocilizumab infusions due to an AE or SAE were analyzed.
Time Frame
Baseline (Day 1) and Weeks 4, 8, 12, 16, 20, and 24
Title
Percentage of Participants Discontinuing Tocilizumab for Other Reasons
Description
Participants that stopped the administration of tocilizumab and discontinued the study prematurely due to reasons other than an AE or SAE were analyzed.
Time Frame
Baseline and Weeks, 4, 8, 12, 16, 20, and 24
Title
Percentage of Participants With Increased Liver Enzyme Values of Greater Than (>)1.5 Times, or >3 Times, or >5 Times Over the Upper Limit of Normal (ULN) by Visit Among Participants Who Completed All Visits
Description
Increased liver enzyme values defined as Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) values of >1.5 times, or >3 times, or >5 times over the ULN. Almost none of the participants had increased measurements of AST, thus only values of ALT were presented. None of the participants presented with increased values of ALT above 3 or 5 ULN at any of the visits.
ITT Completers is defined as a subset of the participants in the ITT population who completed all study visits.
Time Frame
Baseline and Weeks 4, 8, 12, 16, 20, and 24
Title
Percentage of Participants With Increased Lipid Values by Visit Among Participants Who Completed All Visits
Description
Increased levels of high density lipoproteins (HDL) equal to or greater than (≥)1.5 millimoles per liter (mmol/L), and low density lipoproteins (LDL) ≥4.1 mmol/L, and total cholesterol ≥5.1 mmol/L, are defined according to the Adult Treatment Panel III (ATP-III) guidelines.
Time Frame
Screening and Weeks 4, 8, 12, 16, 20, and 24
Title
Percentage of Participants With a Reduction of at Least 1.2 Points in Disease Activity Score Based on 28-Joint Count (DAS28) by Visit Among Participants Who Completed All Visits
Description
Improvement in Rheumatoid Arthritis (RA) disease activity was measured by the DAS28 score, which is an index combining measurements of swollen and tender joints, acute phase response High sensitivity C-Reactive Protein (hsCRP), and global assessment of disease activity by the participant. A clinically meaningful improvement was defined as a reduction of at least 1.2 units in the DAS28 score during the study period. A low disease activity was defined as a DAS28 score less than (<)3.2, and remission was defined as a DAS28 score <2.6.
Time Frame
Weeks 4, 8, 12, 16, 20, and 24
Title
Percentage of Participants Achieving a DAS28 Score Below 3.2 (Low Disease Activity) by Visit Among Participants Who Completed All Visits
Description
Improvement in RA disease activity was measured by the DAS28 score, which is an index combining measurements of swollen and tender joints, acute phase response hsCRP, and global assessment of disease activity by the participant. A clinically meaningful improvement was defined as a reduction of at least 1.2 units in the DAS28 score during the study period. A low disease activity was defined as a DAS28 score <3.2, and remission was defined as a DAS28 score <2.6.
Time Frame
Weeks 4, 8, 12, 16, 20, and 24
Title
Percentage of Participants Achieving a DAS28 Score Below 2.6 (Remission) by Visit Among Participants Who Completed All Visits
Description
Improvement in RA disease activity was measured by the DAS28 score, which is an index combining measurements of swollen and tender joints, acute phase response hsCRP, and global assessment of disease activity by the participant. A clinically meaningful improvement was defined as a reduction of at least 1.2 units in the DAS28 score during the study period. A low disease activity was defined as a DAS28 score <3.2, and remission was defined as a DAS28 score <2.6.
Time Frame
Weeks 4, 8, 12, 16, 20, and 24
Title
DAS28 Score by Visit Among Participants Who Completed All Visits
Description
Improvement in RA disease activity was measured by the DAS28 score, which is an index combining measurements of swollen and tender joints, acute phase response hsCRP, and global assessment of disease activity by the participant. A clinically meaningful improvement was defined as a reduction of at least 1.2 units in the DAS28 score during the study period. A low disease activity was defined as a DAS28 score <3.2, and remission was defined as a DAS28 score <2.6.
Time Frame
Baseline, Weeks, 4, 8, 12, 16, 20, and 24
Title
Percentage of Participants Achieving American College of Rheumatology 20 Percent (%) Improvement (ACR20 Response) by Visit Among Participants Who Completed All Visits
Description
ACR20 response is defined as an improvement of ≥20% in swollen joint count (SJC; 66 joints) and tender joint count (TJC; 68 joints) as well as ≥20% improvement in at least 3 of the following 5 remaining ACR assessments: Patient Global Assessment of Pain; Patient Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; Health Assessment Questionnaire - Disability Index (HAQ-DI); and acute phase reactive factors (Erythrocyte Sedimentation Rate [ESR] or C-Reactive Protein [CRP]).
Time Frame
Weeks 4, 8, 12, 16, 20, and 24
Title
Percentage of Participants Achieving ACR 50% Improvement (ACR50 Response) by Visit Among Participants Who Completed All Visits
Description
ACR50 response is defined as an improvement of ≥50% in SJC (66 joints) and TJC (68 joints) as well as ≥50% improvement in at least 3 of the following 5 remaining ACR assessments: Patient Global Assessment of Pain; Patient Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; HAQ-DI; and acute phase reactive factors (ESR or CRP).
Time Frame
Weeks, 4, 8, 12, 16, 20, and 24
Title
Percentage of Participants Achieving ACR 70% Improvement (ACR70 Response) by Visit, Among Participants Who Completed All Visits
Description
ACR70 response is defined as an improvement of ≥70% in SJC (66 joints) and TJC (68 joints) as well as ≥70% improvement in at least 3 of the following 5 remaining ACR assessments: Patient Global Assessment of Pain; Patient Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; HAQ-DI; and acute phase reactive factors (ESR or CRP).
Time Frame
Weeks 4, 8, 12, 16, 20 and 24
Title
Percentage of Participants Achieving ACR 90% Improvement (ACR90 Response) by Visit Among Participants Who Completed All Visits
Description
ACR90 response is defined as an improvement of ≥90% in SJC (66 joints) and TJC (68 joints) as well as ≥90% improvement in at least 3 of the following 5 remaining ACR assessments: Patient Global Assessment of Pain; Patient Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; HAQ-DI; and acute phase reactive factors (ESR or CRP).
Time Frame
Weeks 4, 8, 12, 16, 20 and 24
Title
High Sensitivity C-Reactive Protein (hsCRP) Levels by Visit Among Participants Who Completed All Visits
Description
hsCRP is a marker for inflammation and is measured in milligrams per liter (mg/L). High levels of this protein indicate inflammation in diseases such as RA.
Time Frame
Screening, Baseline, Weeks 4, 8, 12, 16, 20, and 24
Title
Modified Health Assessment Questionnaire (M-HAQ) Score by Visit Among Participants Who Completed All Visits
Description
M-HAQ is a self-reported, valid assessment of functional disability in RA. Assessment based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. Scores range 0 to 3; without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3.
Time Frame
Baseline, Weeks 4, 8, 12, 20, and 24
Title
Percentage of Participants With Improvement of at Least 0.22 Units in M-HAQ Compared to Baseline Per Visit Among Participants Who Completed All Visits
Description
M-HAQ is a self-reported, valid assessment of functional disability in RA. Assessment based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. Scores range 0 to 3; without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3.
Time Frame
Weeks 4, 8. 12, 20, and 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult patients, at least 18 years of age, inclusive
Diagnosis of rheumatoid arthritis of at least 6 months duration
Moderate to severe active rheumatoid arthritis (DAS28 >/=3.2)
Patients received at least 1 disease-modifying anti-rheumatic drug (DMARD) and/or 1 or more TNFalfa-inhibitors over a period of at least 8 weeks
Exclusion Criteria:
Major surgery (including joint surgery) within 8 weeks prior to screening or planned surgery within 6 months following randomization
Rheumatic autoimmune disease other than rheumatoid arthritis
Prior history of or current inflammatory joint disease other than rheumatoid arthritis
Functional class IV (ACR criteria)
History of severe allergic reaction to human, humanized or murine monoclonal antibodies
Known active current or history of recurrent infection (including tuberculosis)
Primary or secondary immunodeficiency (history of or currently active)
Body weight >150 kg
Previous treatment with any cell-depleting therapies
Previous treatment with tocilizumab
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
Alborg
ZIP/Postal Code
9000
Country
Denmark
City
Frederiksberg
ZIP/Postal Code
2000
Country
Denmark
City
Hellerup
ZIP/Postal Code
2900
Country
Denmark
City
Holbæk
ZIP/Postal Code
4300
Country
Denmark
City
Odense
ZIP/Postal Code
5000
Country
Denmark
City
Silkeborg
ZIP/Postal Code
8600
Country
Denmark
City
Svendborg
ZIP/Postal Code
5700
Country
Denmark
City
Reykjavik
ZIP/Postal Code
108
Country
Iceland
12. IPD Sharing Statement
Learn more about this trial
A Study in Patients With Moderate to Severe Active Rheumatoid Arthritis Comparing Different Infusion Durations of RoActemra/Actemra (Tocilizumab) Treatment
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