Back to resultsA Long-Term Extension Study of WA22763 and NA25220 of Subcutaneous RoActemra/Actemra (Tocilizumab) in Patients With Moderate to Severe Rheumatoid Arthritis
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 3
Locations
Spain
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 have completed the 97-week WA22762 or 96-week NA25220 core study on subcutaneous or intravenous RoActemra/Actemra and based on the investigator's judgment may continue to benefit from RoActemra/Actemra treatment in this study investigating the subcutaneous formulation
- Oral corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDS) up to the maximum recommended dose are permitted if on a stable dose regimen for >/= 4 weeks prior to baseline
- Permitted non-biological disease-modifying anti-rheumatic drugs (DMARDs) are allowed
- Receiving treatment on an outpatient basis
- Females of childbearing potential and males with female partners of childbearing potential must agree to use reliable means of contraception
Exclusion Criteria:
- Participants who have prematurely withdrawn from the WA22762 or NA25220 core studies for any reason
- Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies
- History of severe allergic or anaphylactic reactions to human, humanized or mural monoclonal antibodies
- Evidence of serious uncontrolled concomitant disease
- Current liver disease as determined by the principal investigator
- History of diverticulitis, diverticulosis requiring antibiotic treatment or chronic ulcerative lower gastrointestinal (GI) disease such as Crohn's disease, ulcerative colitis or other symptomatic lower GI conditions that might predispose to perforations
- Known active current or history of recurrent infections
- Any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
- Active tuberculosis requiring treatment within the previous 3 years
- Primary or secondary immunodeficiency (history of or currently active)
- Pregnant or breast feeding women
- Body weight > 150 kilogram (kg)
- Inadequate renal, hepatic or hematologic function
- Positive for hepatitis B or hepatitis C
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Tocilizumab Subcutaneous (SC)
Arm Description
Participants received Tocilizumab 162 milligram (mg) given as 0.9 milliliter (mL) of a 180 milligram per milliliter (mg/mL) solution administered once a week (for participants entering from NCT01194414) or once every two weeks (for participants entering from NCT01232569) by SC injection and as a single fixed dose irrespective of body weight.
Outcomes
Primary Outcome Measures
Percentage of Participants With an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a clinical investigation participant that was administered study drug, regardless of causal attribution.
Percentage of Participants Withdrawn From the Study Due to Lack of Therapeutic Response
Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 48
The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis. The index included swollen joint count (SJC), tender joint count (TJC), acute phase response (ESR or high sensitivity C-reactive protein [hsCRP]) and general health status (GH). For this study, ESR was used to calculate DAS28 score. The index was calculated using the following formula: DAS28 = (0.56 × √[TJC 28]) + (0.28 × √[SJC 28]) + (0.7 × ln[ESR]) + (0.014 × GH). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. Change in DAS28ESR=DAS28-ESR at Week 48 - DAS28-ESR at Baseline.
Change From Baseline in DAS28-ESR at Week 96
The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis. The index included SJC, TJC, acute phase response (ESR or high sensitivity C-reactive protein [hsCRP]) and general health status. For this study, ESR was used to calculate DAS28 score. The index was calculated using the following formula: DAS28 = (0.56 × √[TJC28]) + (0.28 × √[SJC28]) + (0.7 × ln[ESR]) + (0.014 × GH). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. Change in DAS28ESR=DAS28-ESR at Week 96 - DAS28-ESR at Baseline.
Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 48
The SDAI was the numerical sum of five outcome parameter: SJC and TJC, Patient Global Assessment of Disease Activity (PGA) and Investigator Global Assessment of Disease Activity (IGA), and level of hsCRP. The index was calculated using the following formula SDAI = TJC28 + SJC28 + PGA + IGA + CRP. Change in SDAI = SDAI at Week 48 - SDAI at Baseline. SDAI total score = 0-86. SDAI <=3.3 indicates clinical remission, >3.4 to 11 = low disease activity, >11 to 26 = moderate disease activity, and >26 = high (or severe) disease activity. Here, n signifies the number of subjects evaluable at the specified time points.
Change From Baseline in SDAI at Week 96
The SDAI was the numerical sum of five outcome parameter: SJC and TJC, PGA and IGA, and level of hsCRP. The index was calculated using the following formula SDAI = TJC28 + SJC28 + PGA + IGA + CRP. Change in SDAI = SDAI at Week 96 - SDAI at Baseline. SDAI total score = 0-86. SDAI <=3.3 indicates clinical remission, >3.4 to 11 = low disease activity, >11 to 26 = moderate disease activity, and >26 = high (or severe) disease activity.
Change From Baseline in Total Tender Joint Count (TJC) at Week 48
An assessment of 66 joints for swelling and 68 joints for tenderness was made. Joints were assessed and classified as tender/not tender and swollen/not swollen by pressure and joint manipulation on physical examination. A smaller number indicated improvement. Here, 'n' represents the number of participants with a measure at specified time point.
Change From Baseline in Total TJC at Week 96
An assessment of 66 joints for swelling and 68 joints for tenderness was made. Joints were assessed and classified as tender/not tender and swollen/not swollen by pressure and joint manipulation on physical examination. A smaller number indicated improvement.
Change From Baseline in Swollen Joint Count (SJC) at Week 48
An assessment of 66 joints for swelling and 68 joints for tenderness was made. Joints were assessed and classified as tender/not tender and swollen/not swollen by pressure and joint manipulation on physical examination. A negative number indicated improvement.
Change From Baseline in SJC at Week 96
An assessment of 66 joints for swelling and 68 joints for tenderness was made. Joints were assessed and classified as tender/not tender and swollen/not swollen by pressure and joint manipulation on physical examination. Change in SJC = SJC at Week 96 - SJC at Baseline. A negative number indicated improvement.
Secondary Outcome Measures
Percentage of Participants With Remission (DAS28 <2.6 or SDAI </=3.3) at Weeks 48 and 96
Percentage of Participants With Disease-Modifying Antirheumatic Drugs (DMARDs)/Corticosteroid Dose Reductions and/or Discontinuation
Patient Global Visual Analog Score (VAS) at Specified Time Points
This assessment represents the patient's overall assessment of their current disease activity on a 100 millimeter (mm) horizontal VAS. The extreme left end of the line should be described as "no disease activity" (symptom free and no arthritis symptoms) and the extreme right end as "maximum disease activity" (maximum arthritis disease activity). Scores ranged from 0 to 100 with a higher score indicating more disease activity. A negative change score indicated less disease activity.
Patient Pain VAS Score at Specified Time Points
This assessment represents the patient's assessment of his/her current level of pain on a 100 mm horizontal VAS. The extreme left end of the line should be described as "no pain" and the extreme right end as "unbearable pain". Scores ranged from 0 to 100 with a higher score indicating more pain. A negative change score indicated less pain.
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Specified Time Points
The HAQ-DI is a questionnaire specific for rheumatoid arthritis and consists of 20 questions referring to 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Minimum score was 0, maximum score was 3. A smaller score indicated improvement.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01772316
Brief Title
A Long-Term Extension Study of WA22763 and NA25220 of Subcutaneous RoActemra/Actemra (Tocilizumab) in Patients With Moderate to Severe Rheumatoid Arthritis
Official Title
A Multicenter, Open-label, Long-term Extension Study of WA22762 and NA25220 to Evaluate Safety and Efficacy of Subcutaneous Tocilizumab in Patients With Moderate to Severe Rheumatoid Arthritis
Study Type
Interventional
2. Study Status
Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
December 2012 (undefined)
Primary Completion Date
May 2015 (Actual)
Study Completion Date
May 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This multicenter, open-label, single arm, long-term extension study will evaluate the safety and efficacy of RoActemra/Actemra (tocilizumab) in participants with moderate to severe rheumatoid arthritis who have completed the 97-week WA22762 or the 96-week NA25220 core study. Participants will receive RoActemra/Actemra 162 milligram (mg) subcutaneously weekly (for participants entering from WA22762) or every two weeks (for participants entering from NA25220) for 96 weeks, with telephone call follow-up visits at Weeks 100 and 104.
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
47 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tocilizumab Subcutaneous (SC)
Arm Type
Experimental
Arm Description
Participants received Tocilizumab 162 milligram (mg) given as 0.9 milliliter (mL) of a 180 milligram per milliliter (mg/mL) solution administered once a week (for participants entering from NCT01194414) or once every two weeks (for participants entering from NCT01232569) by SC injection and as a single fixed dose irrespective of body weight.
Intervention Type
Drug
Intervention Name(s)
tocilizumab
Other Intervention Name(s)
Roactemra
Intervention Description
162 mg subcutaneously weekly or every two weeks, 96 weeks
Primary Outcome Measure Information:
Title
Percentage of Participants With an Adverse Event (AE)
Description
An AE was defined as any untoward medical occurrence in a clinical investigation participant that was administered study drug, regardless of causal attribution.
Time Frame
Baseline up to follow-up (Week 104)
Title
Percentage of Participants Withdrawn From the Study Due to Lack of Therapeutic Response
Time Frame
Baseline up to follow-up (Week 104)
Title
Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 48
Description
The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis. The index included swollen joint count (SJC), tender joint count (TJC), acute phase response (ESR or high sensitivity C-reactive protein [hsCRP]) and general health status (GH). For this study, ESR was used to calculate DAS28 score. The index was calculated using the following formula: DAS28 = (0.56 × √[TJC 28]) + (0.28 × √[SJC 28]) + (0.7 × ln[ESR]) + (0.014 × GH). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. Change in DAS28ESR=DAS28-ESR at Week 48 - DAS28-ESR at Baseline.
Time Frame
Baseline, Week 48
Title
Change From Baseline in DAS28-ESR at Week 96
Description
The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis. The index included SJC, TJC, acute phase response (ESR or high sensitivity C-reactive protein [hsCRP]) and general health status. For this study, ESR was used to calculate DAS28 score. The index was calculated using the following formula: DAS28 = (0.56 × √[TJC28]) + (0.28 × √[SJC28]) + (0.7 × ln[ESR]) + (0.014 × GH). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. Change in DAS28ESR=DAS28-ESR at Week 96 - DAS28-ESR at Baseline.
Time Frame
Baseline, Week 96
Title
Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 48
Description
The SDAI was the numerical sum of five outcome parameter: SJC and TJC, Patient Global Assessment of Disease Activity (PGA) and Investigator Global Assessment of Disease Activity (IGA), and level of hsCRP. The index was calculated using the following formula SDAI = TJC28 + SJC28 + PGA + IGA + CRP. Change in SDAI = SDAI at Week 48 - SDAI at Baseline. SDAI total score = 0-86. SDAI <=3.3 indicates clinical remission, >3.4 to 11 = low disease activity, >11 to 26 = moderate disease activity, and >26 = high (or severe) disease activity. Here, n signifies the number of subjects evaluable at the specified time points.
Time Frame
Baseline, Week 48
Title
Change From Baseline in SDAI at Week 96
Description
The SDAI was the numerical sum of five outcome parameter: SJC and TJC, PGA and IGA, and level of hsCRP. The index was calculated using the following formula SDAI = TJC28 + SJC28 + PGA + IGA + CRP. Change in SDAI = SDAI at Week 96 - SDAI at Baseline. SDAI total score = 0-86. SDAI <=3.3 indicates clinical remission, >3.4 to 11 = low disease activity, >11 to 26 = moderate disease activity, and >26 = high (or severe) disease activity.
Time Frame
Baseline, Week 96
Title
Change From Baseline in Total Tender Joint Count (TJC) at Week 48
Description
An assessment of 66 joints for swelling and 68 joints for tenderness was made. Joints were assessed and classified as tender/not tender and swollen/not swollen by pressure and joint manipulation on physical examination. A smaller number indicated improvement. Here, 'n' represents the number of participants with a measure at specified time point.
Time Frame
Baseline, Week 48
Title
Change From Baseline in Total TJC at Week 96
Description
An assessment of 66 joints for swelling and 68 joints for tenderness was made. Joints were assessed and classified as tender/not tender and swollen/not swollen by pressure and joint manipulation on physical examination. A smaller number indicated improvement.
Time Frame
Baseline, Week 96
Title
Change From Baseline in Swollen Joint Count (SJC) at Week 48
Description
An assessment of 66 joints for swelling and 68 joints for tenderness was made. Joints were assessed and classified as tender/not tender and swollen/not swollen by pressure and joint manipulation on physical examination. A negative number indicated improvement.
Time Frame
Baseline, Week 48
Title
Change From Baseline in SJC at Week 96
Description
An assessment of 66 joints for swelling and 68 joints for tenderness was made. Joints were assessed and classified as tender/not tender and swollen/not swollen by pressure and joint manipulation on physical examination. Change in SJC = SJC at Week 96 - SJC at Baseline. A negative number indicated improvement.
Time Frame
Baseline, Week 96
Secondary Outcome Measure Information:
Title
Percentage of Participants With Remission (DAS28 <2.6 or SDAI </=3.3) at Weeks 48 and 96
Time Frame
Week 48, Week 96
Title
Percentage of Participants With Disease-Modifying Antirheumatic Drugs (DMARDs)/Corticosteroid Dose Reductions and/or Discontinuation
Time Frame
Randomization of first participant to clinical cutoff date (19MAY2015) (approximately 29 months)
Title
Patient Global Visual Analog Score (VAS) at Specified Time Points
Description
This assessment represents the patient's overall assessment of their current disease activity on a 100 millimeter (mm) horizontal VAS. The extreme left end of the line should be described as "no disease activity" (symptom free and no arthritis symptoms) and the extreme right end as "maximum disease activity" (maximum arthritis disease activity). Scores ranged from 0 to 100 with a higher score indicating more disease activity. A negative change score indicated less disease activity.
Time Frame
Baseline, Week 48, Week 96
Title
Patient Pain VAS Score at Specified Time Points
Description
This assessment represents the patient's assessment of his/her current level of pain on a 100 mm horizontal VAS. The extreme left end of the line should be described as "no pain" and the extreme right end as "unbearable pain". Scores ranged from 0 to 100 with a higher score indicating more pain. A negative change score indicated less pain.
Time Frame
Baseline, Week 48, Week 96
Title
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Specified Time Points
Description
The HAQ-DI is a questionnaire specific for rheumatoid arthritis and consists of 20 questions referring to 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Minimum score was 0, maximum score was 3. A smaller score indicated improvement.
Time Frame
Baseline, Week 48, Week 96
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 have completed the 97-week WA22762 or 96-week NA25220 core study on subcutaneous or intravenous RoActemra/Actemra and based on the investigator's judgment may continue to benefit from RoActemra/Actemra treatment in this study investigating the subcutaneous formulation
Oral corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDS) up to the maximum recommended dose are permitted if on a stable dose regimen for >/= 4 weeks prior to baseline
Permitted non-biological disease-modifying anti-rheumatic drugs (DMARDs) are allowed
Receiving treatment on an outpatient basis
Females of childbearing potential and males with female partners of childbearing potential must agree to use reliable means of contraception
Exclusion Criteria:
Participants who have prematurely withdrawn from the WA22762 or NA25220 core studies for any reason
Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies
History of severe allergic or anaphylactic reactions to human, humanized or mural monoclonal antibodies
Evidence of serious uncontrolled concomitant disease
Current liver disease as determined by the principal investigator
History of diverticulitis, diverticulosis requiring antibiotic treatment or chronic ulcerative lower gastrointestinal (GI) disease such as Crohn's disease, ulcerative colitis or other symptomatic lower GI conditions that might predispose to perforations
Known active current or history of recurrent infections
Any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
Active tuberculosis requiring treatment within the previous 3 years
Primary or secondary immunodeficiency (history of or currently active)
Pregnant or breast feeding women
Body weight > 150 kilogram (kg)
Inadequate renal, hepatic or hematologic function
Positive for hepatitis B or hepatitis C
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
Merida
State/Province
Badajoz
ZIP/Postal Code
06800
Country
Spain
City
Santander
State/Province
Cantabria
ZIP/Postal Code
39008
Country
Spain
City
La Coruna
State/Province
La Coruña
ZIP/Postal Code
15006
Country
Spain
City
Santiago De Compostela
State/Province
La Coruña
ZIP/Postal Code
15706
Country
Spain
City
La Laguna
State/Province
Tenerife
ZIP/Postal Code
38320
Country
Spain
City
Valenica
State/Province
Valencia
ZIP/Postal Code
46009
Country
Spain
City
Barakaldo
State/Province
Vizcaya
ZIP/Postal Code
48903
Country
Spain
City
Bilbao
State/Province
Vizcaya
ZIP/Postal Code
48013
Country
Spain
City
Madrid
ZIP/Postal Code
28007
Country
Spain
City
Madrid
ZIP/Postal Code
28046
Country
Spain
City
Malaga
ZIP/Postal Code
29009
Country
Spain
City
Sevilla
ZIP/Postal Code
41009
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
A Long-Term Extension Study of WA22763 and NA25220 of Subcutaneous RoActemra/Actemra (Tocilizumab) in Patients With Moderate to Severe Rheumatoid Arthritis
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