Back to resultsA Long-Term Extension Study to WA19926 (NCT01007435) of Tocilizumab in Participants With Early, Moderate to Severe Rheumatoid Arthritis
Primary Purpose
Rheumatoid Arthritis
Status
Terminated
Phase
Phase 3
Locations
Poland
Study Type
Interventional
Intervention
Tocilizumab
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
Eligibility Criteria
Inclusion Criteria:
- Participants who complete WA19926 core study (visit at Week 104 and two follow-up telephone visits) and who may benefit from study drug treatment 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
- Receiving treatment on an outpatient basis
- Females of child-bearing potential must agree to use at least one adequate method of contraception as defined by protocol during the treatment period
Exclusion Criteria:
- Pregnant women
- Participants who have prematurely withdrawn from the WA19926 study for any reason
- Treatment with any investigational agent or cell depleting therapies since last administration of study drug in the WA19926 core study
- Treatment with an anti-tumor necrosis factor (TNF) or anti-interleukin (IL)1 agent, or a T-cell co-stimulation modulator since the last administration of the study drug in the WA19926 core study
- Immunization with a live/attenuated vaccine since the last administration of study drug in the WA19926 core study
- Diagnosis since visit at Week 104 of the core WA19926 study of rheumatic autoimmune disease other than rheumatoid arthritis
- Diagnosis since visit at Week 104 of the core WA19926 study of inflammatory joint disease other than rheumatoid arthritis
- Evidence of serious uncontrolled concomitant disease or disorder
- Known active or history of recurrent infection
- Current liver disease as determined by Investigator
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Tocilizumab
Arm Description
Participants will receive tocilizumab 8 milligrams per kilogram (mg/kg) intravenous infusion every 4 weeks up to 104 weeks.
Outcomes
Primary Outcome Measures
Percentage of Participants With Adverse Events (AEs), AEs of Special Interest and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs include serious as well as non-serious AEs. AEs of special interest included: Infections including all opportunistic infections and non-serious infections as defined by those treated with IV anti-infectives; Myocardial infarction/acute coronary syndrome; Gastrointestinal perforations and related events; Malignancies; Anaphylaxis/Hypersensitivity reactions; Demyelinating disorders; Stroke; Bleeding events; and Hepatic events.
Secondary Outcome Measures
Change From Baseline in Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) Score
DAS28-ESR was calculated from swollen joint count and tender joint count using 28 joints count, erythrocyte sedimentation rate (ESR, in millimeters per hour [mm/hour]) and patient global assessment (PtGA) of disease activity (participant rated arthritis activity assessment on a 0 to 100 millimeter [mm] visual analog scale [VAS]; higher scores indicating greater affectation due to disease activity). Total DAS28-ESR transformed score range: 0 to approximately 10, higher score=more disease activity. Participants who completed the study, or discontinued the study as per sponsor discretion due to marketing authorization approval, were included in End of Study Visit which was Week 104. Participants who withdrew from the study for the reason other than sponsor discretion due to marketing authorization approval, were included in Early Withdrawal Visit. Participants with "Unspecified" reason of discontinuation were excluded for change from baseline analysis.
Change From Baseline in Total Tender Joint Counts (28 Joints)
The number of tender joints was recorded on the joint assessment form, no tenderness = 0, tenderness = 1, for 28 joints and joints were classified as tender/not tender giving a total possible tender joint count of 0 to 28. Participants who completed the study, or discontinued the study as per sponsor discretion due to marketing authorization approval, were included in End of Study Visit which was Week 104. Participants who withdrew from the study for the reason other than sponsor discretion due to marketing authorization approval, were included in Early Withdrawal Visit. Participants with "Unspecified" reason of discontinuation were excluded for change from baseline analysis.
Change From Baseline in Total Swollen Joint Counts (28 Joints)
The number of swollen joints was recorded on the joint assessment form, no swelling = 0, swelling =1, for 28 joints and were classified as swollen/not swollen giving a total possible swollen joint count of 0 to 28. Participants who completed the study, or discontinued the study as per sponsor discretion due to marketing authorization approval, were included in End of Study Visit which was Week 104. Participants who withdrew from the study for the reason other than sponsor discretion due to marketing authorization approval, were included in Early Withdrawal Visit. Participants with "Unspecified" reason of discontinuation were excluded for change from baseline analysis.
Percentage of Participants With Drug-Free Remission
Drug-free remission was defined as having clinical remission (defined as DAS28-ESR score <2.6) for 2 consecutive assessment visits followed by discontinuation of tocilizumab at the second assessment visit. DAS28-ESR was calculated from swollen joint count and tender joint count using 28 joints count, ESR, (mm/hour) and PtGA of disease activity (participant rated arthritis activity assessment on a 0 to 100 mm VAS; higher scores indicating greater affectation due to disease activity). Total DAS28-ESR transformed score range: 0 to approximately 10, higher score=more disease activity.
Percentage of Participants With Clinical Remission
Clinical remission was defined as having DAS28-ESR score <2.6 at any point during the study. DAS28-ESR was calculated from swollen joint count and tender joint count using 28 joints count, ESR, (mm/hour) and PtGA of disease activity (participant rated arthritis activity assessment on a 0 to 100 mm VAS; higher scores indicating greater affectation due to disease activity). Total DAS28-ESR transformed score range: 0 to approximately 10, higher score=more disease activity.
Time to Rheumatoid Arthritis (RA) Flare in Participants Who Had Entered Drug-Free Remission
Time to RA flare was defined as the period of drug-free remission (having DAS28-ESR score <2.6 for 2 consecutive assessment visits followed by discontinuation of tocilizumab at the second assessment visit) until documented RA flare. RA flare was defined as any worsening of the participant's disease activity that, in the opinion of the Investigator, required treatment intensification beyond supportive therapy which could include restarting the study drug.
Change From Baseline in Physician's Global Assessment (PGA) of Disease Activity Using Visual Analog Scale (VAS)
The PGA of disease activity was assessed using a 0 to 100 mm horizontal VAS by the physician. The left-hand extreme of the line equaled 0 mm, and was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equaled 100 mm, and was described as "maximum disease activity" (maximum arthritis disease activity). A negative change from baseline indicated improvement. Participants who completed the study, or discontinued the study as per sponsor discretion due to marketing authorization approval, were included in End of Study Visit which was Week 104. Participants who withdrew from the study for the reason other than sponsor discretion due to marketing authorization approval, were included in Early Withdrawal Visit. Participants with "Unspecified" reason of discontinuation were excluded for change from baseline analysis.
Change From Baseline in PtGA of Disease Activity Using VAS
The PtGA of disease activity was assessed using a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equaled 0 mm, and was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equaled 100 mm, and was described as "maximum disease activity" (maximum arthritis disease activity). A negative change from baseline indicated improvement. Participants who completed the study, or discontinued the study as per sponsor discretion due to marketing authorization approval, were included in End of Study Visit which was Week 104. Participants who withdrew from the study for the reason other than sponsor discretion due to marketing authorization approval, were included in Early Withdrawal Visit. Participants with "Unspecified" reason of discontinuation were excluded for change from baseline analysis.
Change From Baseline in Participant Assessment of Pain Using VAS
Severity of pain was evaluated by a VAS. Participants marked on a 100 mm horizontal VAS the severity of pain that they had experienced because of their RA, ranging from 0 mm (no pain) to 100 mm (unbearable pain). Participants who completed the study, or discontinued the study as per sponsor discretion due to marketing authorization approval, were included in End of Study Visit which was Week 104. Participants who withdrew from the study for the reason other than sponsor discretion due to marketing authorization approval, were included in Early Withdrawal Visit. Participants with "Unspecified" reason of discontinuation were excluded for change from baseline analysis.
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)
The HAQ-DI was a participant self-reported questionnaire for assessing the extent of a participant's functional ability. It consisted of 20 questions in 8 categories (dressing and grooming, rising, eating, walking, reach, grip, hygiene, and carrying out daily activities). Each question had 4 response options, ranging from 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. The HAQ-DI scale was an average of all the scores from all questions and ranged from 0 to 3, where higher scores represented higher disease activity. Participants who completed the study, or discontinued the study as per sponsor discretion due to marketing authorization approval, were included in End of Study Visit which was Week 104. Participants who withdrew from study for reason other than sponsor discretion due to marketing authorization approval, were included in Early Withdrawal Visit. Participants with "Unspecified" reason of discontinuation were excluded for change from baseline analysis.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01665430
Brief Title
A Long-Term Extension Study to WA19926 (NCT01007435) of Tocilizumab 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
February 2018
Overall Recruitment Status
Terminated
Why Stopped
Study was terminated by sponsor due to market authorization of tocilizumab for the study population.
Study Start Date
July 2012 (undefined)
Primary Completion Date
February 2015 (Actual)
Study Completion Date
February 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 multicenter, open-label, single arm long-term extension of study WA19926 will evaluate the safety and efficacy of tocilizumab (RoActemra/Actemra) in participants with early, moderate to severe rheumatoid arthritis who have completed the 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
38 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tocilizumab
Arm Type
Experimental
Arm Description
Participants will receive tocilizumab 8 milligrams per kilogram (mg/kg) intravenous infusion every 4 weeks up to 104 weeks.
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Other Intervention Name(s)
RoActemra/Actemra
Intervention Description
Tocilizumab will be administered at 8 mg/kg intravenous infusion every 4 weeks, up to 104 weeks.
Primary Outcome Measure Information:
Title
Percentage of Participants With Adverse Events (AEs), AEs of Special Interest and Serious Adverse Events (SAEs)
Description
An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs include serious as well as non-serious AEs. AEs of special interest included: Infections including all opportunistic infections and non-serious infections as defined by those treated with IV anti-infectives; Myocardial infarction/acute coronary syndrome; Gastrointestinal perforations and related events; Malignancies; Anaphylaxis/Hypersensitivity reactions; Demyelinating disorders; Stroke; Bleeding events; and Hepatic events.
Time Frame
Baseline up to 112 weeks
Secondary Outcome Measure Information:
Title
Change From Baseline in Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) Score
Description
DAS28-ESR was calculated from swollen joint count and tender joint count using 28 joints count, erythrocyte sedimentation rate (ESR, in millimeters per hour [mm/hour]) and patient global assessment (PtGA) of disease activity (participant rated arthritis activity assessment on a 0 to 100 millimeter [mm] visual analog scale [VAS]; higher scores indicating greater affectation due to disease activity). Total DAS28-ESR transformed score range: 0 to approximately 10, higher score=more disease activity. Participants who completed the study, or discontinued the study as per sponsor discretion due to marketing authorization approval, were included in End of Study Visit which was Week 104. Participants who withdrew from the study for the reason other than sponsor discretion due to marketing authorization approval, were included in Early Withdrawal Visit. Participants with "Unspecified" reason of discontinuation were excluded for change from baseline analysis.
Time Frame
Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit (Week 104), at early withdrawal (up to Week 104)
Title
Change From Baseline in Total Tender Joint Counts (28 Joints)
Description
The number of tender joints was recorded on the joint assessment form, no tenderness = 0, tenderness = 1, for 28 joints and joints were classified as tender/not tender giving a total possible tender joint count of 0 to 28. Participants who completed the study, or discontinued the study as per sponsor discretion due to marketing authorization approval, were included in End of Study Visit which was Week 104. Participants who withdrew from the study for the reason other than sponsor discretion due to marketing authorization approval, were included in Early Withdrawal Visit. Participants with "Unspecified" reason of discontinuation were excluded for change from baseline analysis.
Time Frame
Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit (Week 104), at early withdrawal (up to Week 104)
Title
Change From Baseline in Total Swollen Joint Counts (28 Joints)
Description
The number of swollen joints was recorded on the joint assessment form, no swelling = 0, swelling =1, for 28 joints and were classified as swollen/not swollen giving a total possible swollen joint count of 0 to 28. Participants who completed the study, or discontinued the study as per sponsor discretion due to marketing authorization approval, were included in End of Study Visit which was Week 104. Participants who withdrew from the study for the reason other than sponsor discretion due to marketing authorization approval, were included in Early Withdrawal Visit. Participants with "Unspecified" reason of discontinuation were excluded for change from baseline analysis.
Time Frame
Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit (Week 104), at early withdrawal (up to Week 104)
Title
Percentage of Participants With Drug-Free Remission
Description
Drug-free remission was defined as having clinical remission (defined as DAS28-ESR score <2.6) for 2 consecutive assessment visits followed by discontinuation of tocilizumab at the second assessment visit. DAS28-ESR was calculated from swollen joint count and tender joint count using 28 joints count, ESR, (mm/hour) and PtGA of disease activity (participant rated arthritis activity assessment on a 0 to 100 mm VAS; higher scores indicating greater affectation due to disease activity). Total DAS28-ESR transformed score range: 0 to approximately 10, higher score=more disease activity.
Time Frame
Baseline up to Week 104 (assessed at Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit [Week 104], at early withdrawal [up to 104 weeks])
Title
Percentage of Participants With Clinical Remission
Description
Clinical remission was defined as having DAS28-ESR score <2.6 at any point during the study. DAS28-ESR was calculated from swollen joint count and tender joint count using 28 joints count, ESR, (mm/hour) and PtGA of disease activity (participant rated arthritis activity assessment on a 0 to 100 mm VAS; higher scores indicating greater affectation due to disease activity). Total DAS28-ESR transformed score range: 0 to approximately 10, higher score=more disease activity.
Time Frame
Baseline up to Week 104 (assessed at Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit [Week 104], at early withdrawal [up to 104 weeks])
Title
Time to Rheumatoid Arthritis (RA) Flare in Participants Who Had Entered Drug-Free Remission
Description
Time to RA flare was defined as the period of drug-free remission (having DAS28-ESR score <2.6 for 2 consecutive assessment visits followed by discontinuation of tocilizumab at the second assessment visit) until documented RA flare. RA flare was defined as any worsening of the participant's disease activity that, in the opinion of the Investigator, required treatment intensification beyond supportive therapy which could include restarting the study drug.
Time Frame
Baseline up to Week 104 (assessed at Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit [Week 104], at early withdrawal [up to 104 weeks])
Title
Change From Baseline in Physician's Global Assessment (PGA) of Disease Activity Using Visual Analog Scale (VAS)
Description
The PGA of disease activity was assessed using a 0 to 100 mm horizontal VAS by the physician. The left-hand extreme of the line equaled 0 mm, and was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equaled 100 mm, and was described as "maximum disease activity" (maximum arthritis disease activity). A negative change from baseline indicated improvement. Participants who completed the study, or discontinued the study as per sponsor discretion due to marketing authorization approval, were included in End of Study Visit which was Week 104. Participants who withdrew from the study for the reason other than sponsor discretion due to marketing authorization approval, were included in Early Withdrawal Visit. Participants with "Unspecified" reason of discontinuation were excluded for change from baseline analysis.
Time Frame
Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit (Week 104), at early withdrawal (up to 104 weeks)
Title
Change From Baseline in PtGA of Disease Activity Using VAS
Description
The PtGA of disease activity was assessed using a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equaled 0 mm, and was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equaled 100 mm, and was described as "maximum disease activity" (maximum arthritis disease activity). A negative change from baseline indicated improvement. Participants who completed the study, or discontinued the study as per sponsor discretion due to marketing authorization approval, were included in End of Study Visit which was Week 104. Participants who withdrew from the study for the reason other than sponsor discretion due to marketing authorization approval, were included in Early Withdrawal Visit. Participants with "Unspecified" reason of discontinuation were excluded for change from baseline analysis.
Time Frame
Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit (Week 104), at early withdrawal (up to 104 weeks)
Title
Change From Baseline in Participant Assessment of Pain Using VAS
Description
Severity of pain was evaluated by a VAS. Participants marked on a 100 mm horizontal VAS the severity of pain that they had experienced because of their RA, ranging from 0 mm (no pain) to 100 mm (unbearable pain). Participants who completed the study, or discontinued the study as per sponsor discretion due to marketing authorization approval, were included in End of Study Visit which was Week 104. Participants who withdrew from the study for the reason other than sponsor discretion due to marketing authorization approval, were included in Early Withdrawal Visit. Participants with "Unspecified" reason of discontinuation were excluded for change from baseline analysis.
Time Frame
Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit (Week 104), at early withdrawal (up to 104 weeks)
Title
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)
Description
The HAQ-DI was a participant self-reported questionnaire for assessing the extent of a participant's functional ability. It consisted of 20 questions in 8 categories (dressing and grooming, rising, eating, walking, reach, grip, hygiene, and carrying out daily activities). Each question had 4 response options, ranging from 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. The HAQ-DI scale was an average of all the scores from all questions and ranged from 0 to 3, where higher scores represented higher disease activity. Participants who completed the study, or discontinued the study as per sponsor discretion due to marketing authorization approval, were included in End of Study Visit which was Week 104. Participants who withdrew from study for reason other than sponsor discretion due to marketing authorization approval, were included in Early Withdrawal Visit. Participants with "Unspecified" reason of discontinuation were excluded for change from baseline analysis.
Time Frame
Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, at end of study visit (Week 104), at early withdrawal (up to 104 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants who complete WA19926 core study (visit at Week 104 and two follow-up telephone visits) and who may benefit from study drug treatment 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
Receiving treatment on an outpatient basis
Females of child-bearing potential must agree to use at least one adequate method of contraception as defined by protocol during the treatment period
Exclusion Criteria:
Pregnant women
Participants who have prematurely withdrawn from the WA19926 study for any reason
Treatment with any investigational agent or cell depleting therapies since last administration of study drug in the WA19926 core study
Treatment with an anti-tumor necrosis factor (TNF) or anti-interleukin (IL)1 agent, or a T-cell co-stimulation modulator since the last administration of the study drug in the WA19926 core study
Immunization with a live/attenuated vaccine since the last administration of study drug in the WA19926 core study
Diagnosis since visit at Week 104 of the core WA19926 study of rheumatic autoimmune disease other than rheumatoid arthritis
Diagnosis since visit at Week 104 of the core WA19926 study of inflammatory joint disease other than rheumatoid arthritis
Evidence of serious uncontrolled concomitant disease or disorder
Known active or history of recurrent infection
Current liver disease as determined by Investigator
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
Bytom
ZIP/Postal Code
41-902
Country
Poland
City
Elblag
ZIP/Postal Code
82-300
Country
Poland
City
Poznan
ZIP/Postal Code
60-218
Country
Poland
City
Warszawa
ZIP/Postal Code
02-637
Country
Poland
12. IPD Sharing Statement
Learn more about this trial
A Long-Term Extension Study to WA19926 (NCT01007435) of Tocilizumab in Participants With Early, Moderate to Severe Rheumatoid Arthritis
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