Back to resultsA Long-Term Extension Study of WA19926 on the Safety of Tocilizumab (RoActemra/Actemra) in Participants With Early Moderate to Severe Rheumatoid Arthritis
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Tocilizumab
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
Eligibility Criteria
Inclusion Criteria:
- Adult participants, >/= 18 years of age
- Participants who complete their last WA19926 core study visit (Week 104) and who may benefit from study drug treatment, at baseline or later if they are in remission DAS28 at Week 104 of WA19926, according to the Investigator's assessment
- No current or recent adverse event or laboratory finding preventing the use of the study drug dose of tocilizumab 8 mg/kg at baseline visit
- Women of childbearing potential must agree to use adequate contraception as defined by protocol during and up to 3 months after treatment
Exclusion Criteria:
- Pregnant females
- Participants who have withdrawn prematurely from the WA19926 core study for any reason
- Treatment with any investigational agent or cell-depleting therapies since the last administration of study drug in WA19926
- Treatment with an anti-tumor necrosis factor (TNF) or anti-interleukin (IL) 1 agent, or a T-cell costimulation modulator since the last administration of study drug in WA19926
- Immunization with a live/attenuated vaccine since the last administration of study drug in WA19926
- Diagnosis since last WA19926 visit (Week 104) of rheumatic autoimmune disease other than rheumatoid arthritis
- Diagnosis since last WA19926 visit (Week 104) of inflammatory joint disease other than rheumatoid arthritis
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, including tocilizumab and its excipients
- Evidence of severe uncontrolled concomitant disease or disorder
- Known active or history of recurrent infections
- Active tuberculosis requiring treatment in the previous 3 years
- History of alcohol, drug or chemical abuse since inclusion in the WA19926 study
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Tocilizumab
Arm Description
Tocilizumab 8 milligrams per kilogram (mg/kg) administered intravenously once every 4 weeks during a minimum of 104 weeks.
Outcomes
Primary Outcome Measures
Percentage of Participants With Any Adverse Event (AE)
An AE was defined as any unfavorable 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 any AE that is fatal; life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect in a neonate/infant or significant medical event in the Investigator's judgment. AE of special interest (AESI) includes serious and/or medically significant infectious; myocardial infarction(MI) / acute coronary syndrome (ACS); gastrointestinal (GI) perforation; anaphylaxis / hypersensitivity reactions; demyelinating disorders; stroke; serious and/or medically significant bleeding events; serious and/or medically significant hepatic events; malignancies malignant.
Secondary Outcome Measures
Percentage of Participants With at Least One Clinical Remission Period
Clinical remission: Disease Activity Score Based on 28-joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) less than (<)2.6 and/or Simplified Disease Activity Index (SDAI) less than or equal to (≤)3.3 for a period of at least two consecutive assessment visits (every 12 weeks) over the extension study period. DAS28-ESR was calculated using Swollen Joint Count Based on 28 Joints (SJC28), Tender Joint Count Based on 28 Joints (TJC28), ESR (mm/hour) and patient's global assessment of disease activity (100-millimeter (mm) horizontal visual analog scale with 0=no disease activity to 100=maximum disease activity. DAS28-ESR scores range from 0-10, with higher scores corresponding to greater disease activity. SDAI was calculated using SJC28, TJC28, C-reactive protein (CRP) (milligrams per liter (mg/L)), the patient's global assessment of disease activity and physician's global assessment of disease activity; SDAI scores range from 0-86, where lower scores indicate less disease activity.
Percentage of Participants With at Least One Drug-Free Period
Drug-free remission period was defined as clinical remission for at least 2 consecutive assessment visits (every 12 weeks) AND without tocilizumab administration during this clinical remission period.
Cumulative Time of Remission Per Participant Over the Extension Study Period
Clinical remission was defined as DAS28-ESR <2.6 and/or SDAI ≤3.3 for a period of at least two consecutive assessment visits (every 12 weeks) over the extension study period. DAS28-ESR scores range from 0 to 10, with higher scores corresponding to greater disease activity. SDAI scores range from 0 to 86, where lower scores indicate less disease activity.
Percentage of Participants With at Least 1 Rheumatoid Arthritis (RA) Flare
An RA flare was defined as an increase in DAS28-ESR from the previous available visits of >1.2, or >0.6 if current DAS28-ESR ≥3.2. DAS28-ESR scores range from 0 to 10, with higher scores corresponding to greater disease activity.
Time to RA Flare Following Remission or Drug-Free Remission
Time to RA flare was defined as period of clinical remission or drug-free remission followed by flare of DAS28-ESR (increase in DAS28-ESR from the previous available visits of >1.2, or >0.6 if current DAS28-ESR ≥3.2). In the case of several remission periods for the same participant, the largest period was used.
Change From Day 1 in DAS28-ESR Scores Over Time
DAS28-ESR was calculated using Swollen Joint Count Based on 28 Joints (SJC28), Tender Joint Count Based on 28 Joints (TJC28), ESR (mm/hour) and patient's global assessment of disease activity (100-millimeter (mm) horizontal visual analog scale with 0=no disease activity to 100=maximum disease activity. DAS28-ESR scores range from 0 to 10, with higher scores corresponding to greater disease activity.
Change From Day 1 in Simplified Disease Activity Index (SDAI) Scores Over Time
SDAI was calculated using SJC28, TJC28, C-reactive protein (CRP) (milligrams per liter (mg/L)), and the patient's global assessment of disease activity and physician's global assessment of disease activity; SDAI scores range from 0 to 86, where lower scores indicate less disease activity.
Change From Day 1 in Tender Joint Count Based on 28 Joints (TJC28) Over Time
The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1; total was calculated by adding all the joints for a maximum score of 28 tender joints. Higher scores correspond to greater disease activity.
Change From Day 1 in Swollen Joint Count Based on 28 Joints (SJC28) Over Time
The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1; total was calculated by adding all the joints for a maximum score of 28 swollen joints. Higher scores correspond to greater disease activity.
Erythrocyte Sedimentation Rate (ESR) Over Time
ESR is an direct measure of how much inflammation is in the body. The normal range is 0-22 mm/hour for men and 0-29 mm/hour for women. Higher scores correspond to greater disease activity.
C-reactive Protein (CRP) Level
C-reactive protein (CRP) is a blood test marker for inflammation in the body. Normal CRP levels are below 5 milligrams per liter (mg/L). Higher scores correspond to greater disease activity.
Participants' Global Assessment of Pain (VAS) Score
The participants' global assessment of pain (VAS) was assessed using a 100-mm horizontal VAS with 0=no pain to 100=maximum pain.
Participants' Global Assessment of Disease Activity (VAS) Score
The participants' global assessment of disease activity (VAS) was assessed using a 100-mm horizontal VAS with 0=no disease activity to 100=maximum disease.
Physicians' Global Assessment of Disease Activity (VAS) Score
The physicians' global assessment of disease activity (VAS) was assessed using a 100-mm horizontal VAS with 0=no disease activity to 100=maximum disease.
Percentage of Participants With Health Assessment Questionnaire Disability Index (HAQ-DI) Remission
HAQ-DI remission was defined as HAQ-DI score <0.5.
HAQ-DI is the participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Percentage of Participants With Clinically Meaningful Improvement From Baseline in HAQ-DI
Clinically meaningful improvement was defined as an improvement in HAQ-DI score of ≥0.22.
HAQ-DI is the participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01655381
Brief Title
A Long-Term Extension Study of WA19926 on the Safety of Tocilizumab (RoActemra/Actemra) in Participants With Early Moderate to Severe Rheumatoid Arthritis
Official Title
A Multicenter, Open-label, Single Arm, Long-term Extension Study of WA19926 to Describe Safety During Treatment With Tocilizumab in Patients With Early, Moderate to Severe Rheumatoid Arthritis
Study Type
Interventional
2. Study Status
Record Verification Date
December 2016
Overall Recruitment Status
Completed
Study Start Date
April 2012 (undefined)
Primary Completion Date
July 2015 (Actual)
Study Completion Date
July 2015 (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, multicenter long-term extension study will evaluate the safety and efficacy of tocilizumab (RoActemra/Actemra) in participants with moderate to severe rheumatoid arthritis who have completed the 104-week WA19926 core study. Eligible participants will receive tocilizumab 8 mg/kg intravenously every 4 weeks for up to 104 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
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tocilizumab
Arm Type
Experimental
Arm Description
Tocilizumab 8 milligrams per kilogram (mg/kg) administered intravenously once every 4 weeks during a minimum of 104 weeks.
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Other Intervention Name(s)
RoActemra®, Actemra®
Intervention Description
Tocilizumab 8 mg/kg administered intravenously.
Primary Outcome Measure Information:
Title
Percentage of Participants With Any Adverse Event (AE)
Description
An AE was defined as any unfavorable 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 any AE that is fatal; life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect in a neonate/infant or significant medical event in the Investigator's judgment. AE of special interest (AESI) includes serious and/or medically significant infectious; myocardial infarction(MI) / acute coronary syndrome (ACS); gastrointestinal (GI) perforation; anaphylaxis / hypersensitivity reactions; demyelinating disorders; stroke; serious and/or medically significant bleeding events; serious and/or medically significant hepatic events; malignancies malignant.
Time Frame
Up to 160 weeks
Secondary Outcome Measure Information:
Title
Percentage of Participants With at Least One Clinical Remission Period
Description
Clinical remission: Disease Activity Score Based on 28-joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) less than (<)2.6 and/or Simplified Disease Activity Index (SDAI) less than or equal to (≤)3.3 for a period of at least two consecutive assessment visits (every 12 weeks) over the extension study period. DAS28-ESR was calculated using Swollen Joint Count Based on 28 Joints (SJC28), Tender Joint Count Based on 28 Joints (TJC28), ESR (mm/hour) and patient's global assessment of disease activity (100-millimeter (mm) horizontal visual analog scale with 0=no disease activity to 100=maximum disease activity. DAS28-ESR scores range from 0-10, with higher scores corresponding to greater disease activity. SDAI was calculated using SJC28, TJC28, C-reactive protein (CRP) (milligrams per liter (mg/L)), the patient's global assessment of disease activity and physician's global assessment of disease activity; SDAI scores range from 0-86, where lower scores indicate less disease activity.
Time Frame
Up to approximately 148 weeks
Title
Percentage of Participants With at Least One Drug-Free Period
Description
Drug-free remission period was defined as clinical remission for at least 2 consecutive assessment visits (every 12 weeks) AND without tocilizumab administration during this clinical remission period.
Time Frame
Up to approximately 148 weeks
Title
Cumulative Time of Remission Per Participant Over the Extension Study Period
Description
Clinical remission was defined as DAS28-ESR <2.6 and/or SDAI ≤3.3 for a period of at least two consecutive assessment visits (every 12 weeks) over the extension study period. DAS28-ESR scores range from 0 to 10, with higher scores corresponding to greater disease activity. SDAI scores range from 0 to 86, where lower scores indicate less disease activity.
Time Frame
Up to approximately 148 weeks
Title
Percentage of Participants With at Least 1 Rheumatoid Arthritis (RA) Flare
Description
An RA flare was defined as an increase in DAS28-ESR from the previous available visits of >1.2, or >0.6 if current DAS28-ESR ≥3.2. DAS28-ESR scores range from 0 to 10, with higher scores corresponding to greater disease activity.
Time Frame
Up to approximately 148 weeks
Title
Time to RA Flare Following Remission or Drug-Free Remission
Description
Time to RA flare was defined as period of clinical remission or drug-free remission followed by flare of DAS28-ESR (increase in DAS28-ESR from the previous available visits of >1.2, or >0.6 if current DAS28-ESR ≥3.2). In the case of several remission periods for the same participant, the largest period was used.
Time Frame
Up to approximately 148 weeks
Title
Change From Day 1 in DAS28-ESR Scores Over Time
Description
DAS28-ESR was calculated using Swollen Joint Count Based on 28 Joints (SJC28), Tender Joint Count Based on 28 Joints (TJC28), ESR (mm/hour) and patient's global assessment of disease activity (100-millimeter (mm) horizontal visual analog scale with 0=no disease activity to 100=maximum disease activity. DAS28-ESR scores range from 0 to 10, with higher scores corresponding to greater disease activity.
Time Frame
Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140
Title
Change From Day 1 in Simplified Disease Activity Index (SDAI) Scores Over Time
Description
SDAI was calculated using SJC28, TJC28, C-reactive protein (CRP) (milligrams per liter (mg/L)), and the patient's global assessment of disease activity and physician's global assessment of disease activity; SDAI scores range from 0 to 86, where lower scores indicate less disease activity.
Time Frame
Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140
Title
Change From Day 1 in Tender Joint Count Based on 28 Joints (TJC28) Over Time
Description
The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1; total was calculated by adding all the joints for a maximum score of 28 tender joints. Higher scores correspond to greater disease activity.
Time Frame
Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140
Title
Change From Day 1 in Swollen Joint Count Based on 28 Joints (SJC28) Over Time
Description
The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1; total was calculated by adding all the joints for a maximum score of 28 swollen joints. Higher scores correspond to greater disease activity.
Time Frame
Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140
Title
Erythrocyte Sedimentation Rate (ESR) Over Time
Description
ESR is an direct measure of how much inflammation is in the body. The normal range is 0-22 mm/hour for men and 0-29 mm/hour for women. Higher scores correspond to greater disease activity.
Time Frame
Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140
Title
C-reactive Protein (CRP) Level
Description
C-reactive protein (CRP) is a blood test marker for inflammation in the body. Normal CRP levels are below 5 milligrams per liter (mg/L). Higher scores correspond to greater disease activity.
Time Frame
Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140
Title
Participants' Global Assessment of Pain (VAS) Score
Description
The participants' global assessment of pain (VAS) was assessed using a 100-mm horizontal VAS with 0=no pain to 100=maximum pain.
Time Frame
Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140
Title
Participants' Global Assessment of Disease Activity (VAS) Score
Description
The participants' global assessment of disease activity (VAS) was assessed using a 100-mm horizontal VAS with 0=no disease activity to 100=maximum disease.
Time Frame
Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140
Title
Physicians' Global Assessment of Disease Activity (VAS) Score
Description
The physicians' global assessment of disease activity (VAS) was assessed using a 100-mm horizontal VAS with 0=no disease activity to 100=maximum disease.
Time Frame
Day 1 and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140
Title
Percentage of Participants With Health Assessment Questionnaire Disability Index (HAQ-DI) Remission
Description
HAQ-DI remission was defined as HAQ-DI score <0.5.
HAQ-DI is the participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Time Frame
Baseline and Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128 140
Title
Percentage of Participants With Clinically Meaningful Improvement From Baseline in HAQ-DI
Description
Clinically meaningful improvement was defined as an improvement in HAQ-DI score of ≥0.22.
HAQ-DI is the participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Time Frame
Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, 116, 128, 140
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult participants, >/= 18 years of age
Participants who complete their last WA19926 core study visit (Week 104) and who may benefit from study drug treatment, at baseline or later if they are in remission DAS28 at Week 104 of WA19926, according to the Investigator's assessment
No current or recent adverse event or laboratory finding preventing the use of the study drug dose of tocilizumab 8 mg/kg at baseline visit
Women of childbearing potential must agree to use adequate contraception as defined by protocol during and up to 3 months after treatment
Exclusion Criteria:
Pregnant females
Participants who have withdrawn prematurely from the WA19926 core study for any reason
Treatment with any investigational agent or cell-depleting therapies since the last administration of study drug in WA19926
Treatment with an anti-tumor necrosis factor (TNF) or anti-interleukin (IL) 1 agent, or a T-cell costimulation modulator since the last administration of study drug in WA19926
Immunization with a live/attenuated vaccine since the last administration of study drug in WA19926
Diagnosis since last WA19926 visit (Week 104) of rheumatic autoimmune disease other than rheumatoid arthritis
Diagnosis since last WA19926 visit (Week 104) of inflammatory joint disease other than rheumatoid arthritis
History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, including tocilizumab and its excipients
Evidence of severe uncontrolled concomitant disease or disorder
Known active or history of recurrent infections
Active tuberculosis requiring treatment in the previous 3 years
History of alcohol, drug or chemical abuse since inclusion in the WA19926 study
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
Cahors
ZIP/Postal Code
46005
Country
France
City
Montpellier
ZIP/Postal Code
34295
Country
France
City
Mulhouse
ZIP/Postal Code
68070
Country
France
City
Orleans
ZIP/Postal Code
45032
Country
France
City
Paris
ZIP/Postal Code
75651
Country
France
City
Toulouse
ZIP/Postal Code
31059
Country
France
12. IPD Sharing Statement
Learn more about this trial
A Long-Term Extension Study of WA19926 on the Safety of Tocilizumab (RoActemra/Actemra) in Participants With Early Moderate to Severe Rheumatoid Arthritis
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