Back to resultsA Study of RoActemra/Actemra (Tocilizumab) in Combination With Methotrexate Versus RoActemra/Actemra Monotherapy in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 4
Locations
Spain
Study Type
Interventional
Intervention
methotrexate
methotrexate
placebo
tocilizumab [RoActemra/Actemra]
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
Eligibility Criteria
Inclusion Criteria:
- Adult patients, >/= 18 years of age
- Active moderate to severe rheumatoid arthritis (DAS28 >/= 3.2) at baseline
- Currently receiving methotrexate for at least 12 weeks, at a stable oral dose of at least 15 mg/week for at least 6 weeks prior to treatment (Day 1)
- Body weight < 150 kg
- Oral corticoids must have been at stable dose for at least 25 out of 28 days prior to baseline; maximum dose 10 mg/day
Exclusion Criteria:
- Pregnant or nursing women
- Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months after baseline
- Rheumatic autoimmune disease other than RA
- Functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in Rheumatoid Arthritis
- Prior history of or current inflammatory joint disease other than RA
- Treatment with a biologic agent at any time prior to baseline
- Treatment with traditional DMARDs other than methotrexate within 1 month (for leflunomide 3 months) prior to baseline
- Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline
- Previous treatment with RoActemra/Actemra
- History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
- Known active current or history of recurrent infection
- History of or currently active primary or secondary immunodeficiency
- Active tuberculosis requiring treatment within the previous 3 years
- Positive for HIV infection
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
A
B
Arm Description
Outcomes
Primary Outcome Measures
Change in Disease Activity Score Based on 28-Joint Count (DAS28) From Week 16 to Week 28
The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis (RA). The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (erythrocyte sedimentation rate [ESR] in millimeters per hour [mm/hr]), and general health status (participant global assessment of disease activity using visual analog scale [VAS], range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Secondary Outcome Measures
Percentage of Participants With DAS28 Score Less Than (<) 2.6 at Week 28
The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores indicate worsening. DAS28 <2.6 equals (=) remission.
Percentage of Participants With Clinical Disease Activity Index (CDAI) <2.8 at Week 28
CDAI is the sum of tender and swollen joint count based on 28 joints and the participant and physician global disease assessment (VAS 0-10 centimeters [cm]). CDAI total score 0-76; higher scores = greater affect due to disease activity. CDAI <2.8 = clinical remission.
Percentage of Participants With Simplified Disease Activity Index (SDAI) <3.3 at Week 28
SDAI is calculated by a simple numerical sum of tender and swollen joint count (based on a 28-joint assessment), participant and physician global assessment of disease activity (VAS 0-10 cm), and level of C-reactive protein in milligram per deciliter (mg/dL). SDAI total score 0-86; higher scores = greater affect due to disease activity. SDAI <3.3 = clinical remission.
Change in the Health Assessment Questionnaire Disability Index (HAQ-DI) From Week 16 to Week 28
HAQ-DI: 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.
Change in the Quality of Life Questionnaire (Short Form-12 [SF-12]) From Week 16 to Week 28 in Mental Health
Quality of life questionnaire (SF-12) scores were computed using the scores of 12 questions and ranged from 0 to 100, where a 0 score indicated the lowest level of health measured by the scales and 100 indicated the highest level of health. A negative change from baseline indicated decline in health and higher scores indicated improvement in health.
Change in the Quality of Life Questionnaire (SF-12) From Week 16 to Week 28 in Physical Health
Quality of life questionnaire (SF-12) scores were computed using the scores of 12 questions and ranged from 0 to 100, where a 0 score indicated the lowest level of health measured by the scales and 100 indicated the highest level of health. A negative change from baseline indicated a worsening of quality of life.
Change From Week 16 to Week 28 in Global Assessment of Disease Activity as Assessed With the Visual Analogue Scale (VAS) Performed by Participant
Participants were asked to rate their global assessment of disease activity on a scale ranging from 0=very good to 100=very bad. The scale was represented by a line with 0 at the left edge and 100 at the right edge. The participant was asked to mark the line corresponding to the assessment of their disease activity. The distance from the left edge was measured in mm.
Change From Week 16 to Week 28 in Global Assessment of Disease Activity Assessed Using the VAS Performed by the Investigator
Participants were asked to rate their global assessment of disease activity on a scale ranging from 0=very good to 100=very bad. The scale was represented by a line with 0 at the left edge and 100 at the right edge. The participant was asked to mark the line corresponding to the assessment of their disease activity. The distance from the left edge was measured in mm.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01399697
Brief Title
A Study of RoActemra/Actemra (Tocilizumab) in Combination With Methotrexate Versus RoActemra/Actemra Monotherapy in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate
Official Title
A Multi-center Study of the Safety and Effect on Disease Activity of Tocilizumab (TCZ) in Combination With MTX Versus Tocilizumab Monotherapy in Patients With Rheumatoid Arthritis, With Inadequate Response to MTX (Defined as DAS 28 > 3,2)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2015
Overall Recruitment Status
Completed
Study Start Date
September 2011 (undefined)
Primary Completion Date
May 2014 (Actual)
Study Completion Date
May 2014 (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 randomized, double-blind, parallel-group study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in combination with methotrexate versus RoActemra/Actemra monotherapy in patients with rheumatoid arthritis and an inadequate response to methotrexate. All patients will receive RoActemra/Actemra 8 mg/kg intravenously (iv) every 4 weeks plus oral methotrexate for 16 weeks. Patients achieving low disease activity at Week 16 will be randomized to receive a further 12 weeks of RoActemra/Actemra treatment plus either methotrexate or placebo. Anticipated time on study treatment is 28 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 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
261 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A
Arm Type
Experimental
Arm Title
B
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
methotrexate
Intervention Description
orally, Week 1 - 16
Intervention Type
Drug
Intervention Name(s)
methotrexate
Intervention Description
orally, Week 17-28
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
methotrexate placebo orally, Week 17-28
Intervention Type
Drug
Intervention Name(s)
tocilizumab [RoActemra/Actemra]
Intervention Description
8 mg/kg iv every 4 weeks, 28 weeks
Primary Outcome Measure Information:
Title
Change in Disease Activity Score Based on 28-Joint Count (DAS28) From Week 16 to Week 28
Description
The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis (RA). The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (erythrocyte sedimentation rate [ESR] in millimeters per hour [mm/hr]), and general health status (participant global assessment of disease activity using visual analog scale [VAS], range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Time Frame
Baseline, Week 16, and Week 28
Secondary Outcome Measure Information:
Title
Percentage of Participants With DAS28 Score Less Than (<) 2.6 at Week 28
Description
The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores indicate worsening. DAS28 <2.6 equals (=) remission.
Time Frame
Week 28
Title
Percentage of Participants With Clinical Disease Activity Index (CDAI) <2.8 at Week 28
Description
CDAI is the sum of tender and swollen joint count based on 28 joints and the participant and physician global disease assessment (VAS 0-10 centimeters [cm]). CDAI total score 0-76; higher scores = greater affect due to disease activity. CDAI <2.8 = clinical remission.
Time Frame
Week 28
Title
Percentage of Participants With Simplified Disease Activity Index (SDAI) <3.3 at Week 28
Description
SDAI is calculated by a simple numerical sum of tender and swollen joint count (based on a 28-joint assessment), participant and physician global assessment of disease activity (VAS 0-10 cm), and level of C-reactive protein in milligram per deciliter (mg/dL). SDAI total score 0-86; higher scores = greater affect due to disease activity. SDAI <3.3 = clinical remission.
Time Frame
28 weeks
Title
Change in the Health Assessment Questionnaire Disability Index (HAQ-DI) From Week 16 to Week 28
Description
HAQ-DI: 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
Week 16 and Week 28
Title
Change in the Quality of Life Questionnaire (Short Form-12 [SF-12]) From Week 16 to Week 28 in Mental Health
Description
Quality of life questionnaire (SF-12) scores were computed using the scores of 12 questions and ranged from 0 to 100, where a 0 score indicated the lowest level of health measured by the scales and 100 indicated the highest level of health. A negative change from baseline indicated decline in health and higher scores indicated improvement in health.
Time Frame
Week 16 and Week 28
Title
Change in the Quality of Life Questionnaire (SF-12) From Week 16 to Week 28 in Physical Health
Description
Quality of life questionnaire (SF-12) scores were computed using the scores of 12 questions and ranged from 0 to 100, where a 0 score indicated the lowest level of health measured by the scales and 100 indicated the highest level of health. A negative change from baseline indicated a worsening of quality of life.
Time Frame
Week 16 and Week 28
Title
Change From Week 16 to Week 28 in Global Assessment of Disease Activity as Assessed With the Visual Analogue Scale (VAS) Performed by Participant
Description
Participants were asked to rate their global assessment of disease activity on a scale ranging from 0=very good to 100=very bad. The scale was represented by a line with 0 at the left edge and 100 at the right edge. The participant was asked to mark the line corresponding to the assessment of their disease activity. The distance from the left edge was measured in mm.
Time Frame
Week 16 and Week 28
Title
Change From Week 16 to Week 28 in Global Assessment of Disease Activity Assessed Using the VAS Performed by the Investigator
Description
Participants were asked to rate their global assessment of disease activity on a scale ranging from 0=very good to 100=very bad. The scale was represented by a line with 0 at the left edge and 100 at the right edge. The participant was asked to mark the line corresponding to the assessment of their disease activity. The distance from the left edge was measured in mm.
Time Frame
Week 16 and Week 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult patients, >/= 18 years of age
Active moderate to severe rheumatoid arthritis (DAS28 >/= 3.2) at baseline
Currently receiving methotrexate for at least 12 weeks, at a stable oral dose of at least 15 mg/week for at least 6 weeks prior to treatment (Day 1)
Body weight < 150 kg
Oral corticoids must have been at stable dose for at least 25 out of 28 days prior to baseline; maximum dose 10 mg/day
Exclusion Criteria:
Pregnant or nursing women
Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months after baseline
Rheumatic autoimmune disease other than RA
Functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in Rheumatoid Arthritis
Prior history of or current inflammatory joint disease other than RA
Treatment with a biologic agent at any time prior to baseline
Treatment with traditional DMARDs other than methotrexate within 1 month (for leflunomide 3 months) prior to baseline
Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline
Previous treatment with RoActemra/Actemra
History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
Known active current or history of recurrent infection
History of or currently active primary or secondary immunodeficiency
Active tuberculosis requiring treatment within the previous 3 years
Positive for HIV infection
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Orihuela
State/Province
Alicante
ZIP/Postal Code
03314
Country
Spain
City
Torrevieja
State/Province
Alicante
ZIP/Postal Code
03186
Country
Spain
City
Villajoyosa
State/Province
Alicante
ZIP/Postal Code
03570
Country
Spain
City
Merida
State/Province
Badajoz
ZIP/Postal Code
06800
Country
Spain
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08915
Country
Spain
City
Granollers
State/Province
Barcelona
ZIP/Postal Code
08402
Country
Spain
City
Terrassa
State/Province
Barcelona
ZIP/Postal Code
08221
Country
Spain
City
Cádiz
State/Province
Cadiz
ZIP/Postal Code
11009
Country
Spain
City
Torrelavega
State/Province
Cantabria
ZIP/Postal Code
39300
Country
Spain
City
Villarreal
State/Province
Castellon
ZIP/Postal Code
12540
Country
Spain
City
Menorca
State/Province
Islas Baleares
ZIP/Postal Code
07701
Country
Spain
City
A 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
Las Palmas De Gran Canaria
State/Province
Las Palmas
ZIP/Postal Code
35020
Country
Spain
City
Alcala de Henares
State/Province
Madrid
ZIP/Postal Code
28805
Country
Spain
City
Fuenlabrada
State/Province
Madrid
ZIP/Postal Code
28942
Country
Spain
City
Valdemoro
State/Province
Madrid
ZIP/Postal Code
28342
Country
Spain
City
Cartagena
State/Province
Murcia
ZIP/Postal Code
30203
Country
Spain
City
El Palmar
State/Province
Murcia
ZIP/Postal Code
30120
Country
Spain
City
Vigo
State/Province
Pontevedra
ZIP/Postal Code
36214
Country
Spain
City
Manises
State/Province
Valencia
ZIP/Postal Code
46940
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
Galdakao
State/Province
Vizcaya
ZIP/Postal Code
48960
Country
Spain
City
Albacete
ZIP/Postal Code
02006
Country
Spain
City
Badajoz
ZIP/Postal Code
06080
Country
Spain
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
City
Barcelona
ZIP/Postal Code
08907
Country
Spain
City
Caceres
ZIP/Postal Code
10310
Country
Spain
City
Cordoba
ZIP/Postal Code
14004
Country
Spain
City
Granada
ZIP/Postal Code
18003
Country
Spain
City
Granada
ZIP/Postal Code
18014
Country
Spain
City
Guadalajara
ZIP/Postal Code
19002
Country
Spain
City
Leon
ZIP/Postal Code
24071
Country
Spain
City
Lugo
ZIP/Postal Code
27004
Country
Spain
City
Madrid
ZIP/Postal Code
28007
Country
Spain
City
Madrid
ZIP/Postal Code
28031
Country
Spain
City
Madrid
ZIP/Postal Code
28034
Country
Spain
City
Madrid
ZIP/Postal Code
28040
Country
Spain
City
Madrid
ZIP/Postal Code
28041
Country
Spain
City
Madrid
ZIP/Postal Code
28046
Country
Spain
City
Madrid
ZIP/Postal Code
28905
Country
Spain
City
Malaga
ZIP/Postal Code
29009
Country
Spain
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
City
Sevilla
ZIP/Postal Code
41009
Country
Spain
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
City
Tenerife
ZIP/Postal Code
38010
Country
Spain
City
Toledo
ZIP/Postal Code
45004
Country
Spain
City
Valencia
ZIP/Postal Code
46010
Country
Spain
City
Valencia
ZIP/Postal Code
46017
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
A Study of RoActemra/Actemra (Tocilizumab) in Combination With Methotrexate Versus RoActemra/Actemra Monotherapy in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate
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