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A Study of Subcutaneous RoActemra/Actemra (Tocilizumab) as Monotherapy or in Combination With Methotrexate or Other Non-Biologic DMARDs in Patients With Active Rheumatoid Arthritis

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ClinicalTrials.gov Identifier: NCT01995201
Recruitment Status : Completed
First Posted : November 26, 2013
Results First Posted : January 26, 2018
Last Update Posted : January 26, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE November 1, 2013
First Posted Date  ICMJE November 26, 2013
Results First Submitted Date  ICMJE March 8, 2017
Results First Posted Date  ICMJE January 26, 2018
Last Update Posted Date January 26, 2018
Study Start Date  ICMJE September 2013
Actual Primary Completion Date July 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 20, 2017)
Percentage of Participants Achieving Sustained Clinical Remission, Disease Activity Scale 28 - Erythrocyte Sedimentation Rate <26 (DAS28-ESR <2.6) at Week 20 and Week 24 [ Time Frame: Week 20 and Week 24 ]
The DAS 28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP) and general health status. For this study ESR was used to calculate the DAS 28 score.
Original Primary Outcome Measures  ICMJE
 (submitted: November 21, 2013)
Proportion of patients achieving sustained clinical remission (DAS-ESR <2.6) at Weeks 20 and 24 [ Time Frame: 24 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 20, 2017)
  • Mean Change in Disease Activity Score 28 - Erythrocyte Sedimentation Rate(DAS28-ESR) [ Time Frame: From week 24 up to week 48 ]
    The DAS 28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP) and general health status. For this study ESR was used to calculate the DAS 28 score.
  • Percentage of Patients Allocated in Groups A1 and A2 Who Remain With Clinical Remission Activity (DAS 28 ESR <2.6) up to Week 48 [ Time Frame: From week 28 up to week 48 ]
    The DAS28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP), and general health status. For this study ESR will be used to calculate the DAS28 score.
  • Percentage of Patients Reporting Change in DAS 28 ESR >1.2 Until Week 48 [ Time Frame: From week 28 up to week 48 ]
    The DAS28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP), and general health status. For this study ESR will be used to calculate the DAS28 score.
  • Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24 [ Time Frame: From week 2 until week 24 ]
    The definition of improvement of ACR core set of outcome measures includes an improvement equal or higher to the 20%, 50%, 70%, 90% compared to Baseline in both Swollen Joint Count (SJC) and Tender Joint Count (TJC) as well as in three out of five additional parameters: Physician's Global Assessment of disease activity VAS, patient's Global Assessment of disease activity VAS, patient's assessment of pain VAS, HAQ-DI, and acute phase reactant (either CRP or erythrocyte sedimentation rate [ESR]).
  • Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48 [ Time Frame: From week 28 until week 48 ]
    The definition of improvement of ACR core set of outcome measures includes an improvement equal or higher to the 20%, 50%, 70%, 90% compared to Baseline in both Swollen Joint Count (SJC) and Tender Joint Count (TJC) as well as in three out of five additional parameters: Physician's Global Assessment of disease activity VAS, patient's Global Assessment of disease activity VAS, patient's assessment of pain VAS, HAQ-DI, and acute phase reactant (either CRP or erythrocyte sedimentation rate [ESR]).
  • Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24 [ Time Frame: From week 2 until week 24 ]
    DAS28-based EULAR response criteria were used to measure individual response as good or moderate depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline >1.2 with DAS28 ≤3.2; moderate responders: change from baseline >1.2 with DAS28 >3.2 to ≤5.1 or change from baseline >0.6 to =<1.2 with DAS28 ≤5.1.
  • Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48 [ Time Frame: From week 28 until week 48 ]
    DAS28-based EULAR response criteria were used to measure individual response as good or moderate depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline >1.2 with DAS28 ≤3.2; moderate responders: change from baseline >1.2 with DAS28 >3.2 to ≤5.1 or change from baseline >0.6 to =<1.2 with DAS28 ≤5.1.
  • Mean Change in Clinical Disease Activity Index (CDAI) From Baseline up to Week 24 [ Time Frame: From baseline to Week 24 ]
    Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement.
  • Mean Change From Baseline in Clinical Disease Activity Index (CDAI) up to Week 48 [ Time Frame: From week 24 until week 48 ]
    Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement.
  • Mean Change in Simplified Disease Activity Index (SDAI) From Baseline up to Week 24 [ Time Frame: From baseline to Week 24 ]
    Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =< 3.3 indicates disease remission, > 3.4 to 11 indicates low disease activity, > 11 to 26 indicates moderate disease activity, and > 26 indicates high disease activity.
  • Mean Change in Simplified Disease Activity Index (SDAI) From Week 24 up to Week 48 [ Time Frame: From week 24 until week 48 ]
    Simplified Disease Activity Index (SDAI) which is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =< 3.3 indicates disease remission, > 3.4 to 11 indicates low disease activity, > 11 to 26 indicates moderate disease activity, and > 26 indicates high disease activity.
  • Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 24 [ Time Frame: From baseline to Week 24 ]
    TCJ is a clinical assessment of 68 joints which are classified as tender/not tender by pressure and joint manipulation on physical examination. Joint prosthesis, arthrodesis or fused joints are not be taken into consideration.
  • Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 48 [ Time Frame: From week 24 until week 48 ]
    TCJ is a clinical assessment of 68 joints which are classified as tender/not tender by pressure and joint manipulation on physical examination. Joint prosthesis, arthrodesis or fused joints are not be taken into consideration.
  • Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 24 [ Time Frame: From baseline to Week 24 ]
    SJC is a clinical assessment of 66 joints classified as swollen/not swollen by pressure and joint manipulation on physical examination. Joint prosthesis, arthrodesis or fused joints will not be taken into consideration for swelling.
  • Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 48 [ Time Frame: From week 24 until week 48 ]
    SJC is a clinical assessment of 66 joints classified as swollen/not swollen by pressure and joint manipulation on physical examination. Joint prosthesis, arthrodesis or fused joints will not be taken into consideration for swelling.
  • Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48 [ Time Frame: Week 48 ]
    The DAS 28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP) and general health status. For this study ESR was used to calculate the DAS 28 score.
  • Percentages of Patients With Remission (CDAI<2.8) Until Week 24 [ Time Frame: From baseline to Week 24 ]
    Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement.
  • Percentages of Patients With Remission (CDAI<2.8) Until Week 48 [ Time Frame: From week 28 until week 48 ]
    Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement.
  • Percentages of Patients With Remission (SDAI<3.3) Until Week 24 [ Time Frame: From baseline to Week 24 ]
    Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =< 3.3 indicates disease remission, > 3.4 to 11 indicates low disease activity, > 11 to 26 indicates moderate disease activity, and > 26 indicates high disease activity.
  • Percentages of Patients With Remission (SDAI<3.3) Until Week 48 [ Time Frame: From week 28 until week 48 ]
    Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =< 3.3 indicates disease remission, > 3.4 to 11 indicates low disease activity, > 11 to 26 indicates moderate disease activity, and > 26 indicates high disease activity.
  • Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 24 [ Time Frame: From baseline to Week 24 ]
    The DAS28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP), and general health status. For this study ESR is used to calculate the DAS28 score.
  • Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 48 [ Time Frame: From week 28 until week 48 ]
    The DAS28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP), and general health status. For this study ESR was used to calculate the DAS28 score.
  • Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 24 [ Time Frame: From baseline to Week 24 ]
    Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement.
  • Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 48 [ Time Frame: From week 28 until week 48 ]
    Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement.
  • Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 24 [ Time Frame: From baseline to Week 24 ]
    Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =< 3.3 indicates disease remission, > 3.4 to 11 indicates low disease activity, > 11 to 26 indicates moderate disease activity, and > 26 indicates high disease activity.
  • Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 48 [ Time Frame: From week 28 until week 48 ]
    Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =< 3.3 indicates disease remission, > 3.4 to 11 indicates low disease activity, > 11 to 26 indicates moderate disease activity, and > 26 indicates high disease activity.
  • Safety: Number of Patients Reporting Adverse Events up to Week 24 [ Time Frame: From baseline to Week 24 ]
    Number of patients reporting any treatment emergent adverse event (TEAE), at least one TEAE of special interest, at least one serious TEAE, at least one TEAE leading to dose modification, at least one TEAE leading to discontinuation up to week 24
  • Safety: Number of Patients Reporting Adverse Events up to Week 48 [ Time Frame: From week 24 until week 48 ]
    Number of patients reporting any treatment emergent adverse event (TEAE), at least one TEAE of special interest, at least one serious TEAE, at least one TEAE leading to dose modification, at least one TEAE leading to discontinuation up to week 48
  • Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 24 [ Time Frame: From baseline to Week 24 ]
    Number of patients resulting positive to anti-tocilizumab antibodies test are reported.
  • Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 48 [ Time Frame: From week 24 until week 48 ]
    Number of patients resulting positive to anti-tocilizumab antibodies test are reported.
  • Immunogenicity: TCZ Levels up to Week 24 [ Time Frame: From baseline to Week 24 ]
    Mean concentrations of TCZ in patients' blood are reported.
  • Immunogenicity: TCZ Levels at Week 36 and Early Withdrawal Visit [ Time Frame: week 36 and early withdrawal visit ]
    Mean concentrations of TCZ in patients' blood are reported.
  • Immunogenicity: SIL-6R Levels up to Week 24 [ Time Frame: From baseline to Week 24 ]
    Mean concentration of SIL-6R in patients' blood are reported.
  • Immunogenicity: SIL-6R Levels at Week 36 and Early Withdrawal Visit [ Time Frame: Baseline, Week 36 and Early Withdrawal Visit ]
    Mean concentration of SIL-6R in patients' blood are reported.
  • Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 24 [ Time Frame: From baseline to Week 24 ]
    This patient reported outcome assessment represents the patient's overall assessment of their current disease activity on a 100 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). The line was marked by the participant and the distance from the left edge was recorded and the mean values are reported.
  • Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 48 [ Time Frame: Baseline, from week 28 until week 48 ]
    This patient reported outcome assessment represents the patient's overall assessment of their current disease activity on a 100 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). The line was marked by the participant and the distance from the left edge was recorded and the mean values are reported.
  • Assessment of Pain Reported by the Patient (VAS) Until Week 24 [ Time Frame: From baseline to Week 24 ]
    This patient reported outcome 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".
  • Assessment of Pain Reported by the Patient (VAS) Until Week 48 [ Time Frame: Baseline, from week 28 until week 48 ]
    This patient reported outcome 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".
  • Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 24 [ Time Frame: From baseline to Week 24 ]
    The Stanford HAQ-DI is a patient-oriented outcome assessment questionnaire specific for RA. It consists of 20 questions referring to eight component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3.
  • Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 48 [ Time Frame: Baseline, from week 28 until week 48 ]
    The Stanford HAQ-DI is a patient-oriented outcome assessment questionnaire specific for RA. It consists of 20 questions referring to eight component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3.
  • Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 24 [ Time Frame: From baseline to Week 24 ]
    The symptom-specific measure FACIT-F assesses chronic illness therapy with special emphasis on fatigue in the past 7 days and consists of 5 dimensions: 1) physical well- being, 2) social/family well-being, 3) emotional well-being, 4) functional well-being, and 5) additional concerns. Each of the questions is categorically answered using the scales 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much for a total possible FACIT-F score of 0 to 160. The figures are reversed during score calculations, so that higher score values indicate more favorable conditions.
  • Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 48 [ Time Frame: Baseline, from week 28 until week 48 ]
    The symptom-specific measure FACIT-F assesses chronic illness therapy with special emphasis on fatigue in the past 7 days and consists of 5 dimensions: 1) physical well- being, 2) social/family well-being, 3) emotional well-being, 4) functional well-being, and 5) additional concerns. Each of the questions is categorically answered using the scales 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much for a total possible FACIT-F score of 0 to 160. The figures are reversed during score calculations, so that higher score values indicate more favorable conditions.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 21, 2013)
  • Mean change in DAS28-ESR (Arm A) [ Time Frame: from baseline to Week 48 ]
  • Proportion of patients remaining in clinical remission (Arm A) [ Time Frame: Week 48 ]
  • Rates of flare (defined as change in DAS28-ESR >1.2) (Arm A) [ Time Frame: 48 weeks ]
  • American College of Rheumatology (ACR) response scores [ Time Frame: 48 weeks ]
  • Response according to European League Against Rheumatism (EULAR) response scores [ Time Frame: 48 weeks ]
  • Change in Simplified Disease Activity Index (SDAI)/Clinical Disease Activity Index (CDAI) [ Time Frame: from baseline to Week 48 ]
  • Change in total/swollen joint counts (TJC/SJC) [ Time Frame: from baseline to Week 48 ]
  • Proportion of patients who achieve DAS28-ESR remission (DAS28-ESR <2.6) [ Time Frame: Week 48 ]
  • Proportion of patients who achieve CDAI/SDAI) remission (CDAI <2.8/SDAI <3.3) [ Time Frame: Week 48 ]
  • Proportion of patients who achieve low disease activity based on DAS28-ESR criteria (DAS28-ESR </=3.2) [ Time Frame: Week 48 ]
  • Proportion of patients who achieve low disease activity based on CDAI/SDAI scores (CDAI <10/SDAI <11) [ Time Frame: Week 48 ]
  • Safety: Incidence of adverse events [ Time Frame: 56 weeks ]
  • Immunogenicity: Incidence of anti-tocilizumab antibodies [ Time Frame: 56 weeks ]
  • Patient reported outcomes: Health assessment questionnaires/VAS scales [ Time Frame: 48 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Subcutaneous RoActemra/Actemra (Tocilizumab) as Monotherapy or in Combination With Methotrexate or Other Non-Biologic DMARDs in Patients With Active Rheumatoid Arthritis
Official Title  ICMJE A Phase IIIb Study to Evaluate the Efficacy, Safety and Tolerability of Subcutaneous (SC) Tocilizumab (TCZ) Given as Monotherapy or in Combination With Methotrexate (MTX) or Other Non Biologics DMARDs in Subjects With Rheumatoid Arthritis
Brief Summary This multicenter, open-label study will evaluate the efficacy and safety of subcutaneously administered RoActemra/Actemra (tocilizumab) as monotherapy or in combination with methotrexate or other non-biologic DMARDs in patients with active rheumatoid arthritis and an inadequate response to non-biologic DMARDs or to one anti-TNF. In Phase 1, all patients will receive RoActemra/Actemra 162 mg subcutaneously (sc) weekly for Weeks 1 to 24, with or without methotrexate or other non-biologic DMARDs. For Part 2, patients who achieve sustained clinical DAS28-ESR remission at Weeks 20 and 24 will be randomized to receive RoActemra/Actemra 162 mg sc either weekly or every 2 weeks for Weeks 24 to 48, with or without methotrexate or other non-biologic DMARDs. Patients who do not achieve sustained clinical remission but achieve low disease activity (DAS-ESR </= 3.2) will continue the initial treatment of RoActemra/Actemra 162 mg sc weekly for Weeks 24 to 48, with or without methotrexate or other non-biologic DMARDs.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE
  • Drug: DMARD
    non-biological disease-modifying antirheumatic drugs at stable dose
  • Drug: methotrexate
    stable dose
  • Drug: tocilizumab [RoActemra/Actemra]
    162 mg subcutaneously (SC) qw, Weeks 1-24
  • Drug: tocilizumab [RoActemra/Actemra]
    162 mg SC qw or q2w, Weeks 24-48
  • Drug: tocilizumab [RoActemra/Actemra]
    162 mg SC qw, Weeks 24-48
Study Arms  ICMJE
  • Experimental: Part 1: All patients
    Interventions:
    • Drug: DMARD
    • Drug: methotrexate
    • Drug: tocilizumab [RoActemra/Actemra]
  • Experimental: Part 2 A: Sustained clinical remission
    Interventions:
    • Drug: DMARD
    • Drug: methotrexate
    • Drug: tocilizumab [RoActemra/Actemra]
  • Experimental: Part 2 B: Low disease activity
    Interventions:
    • Drug: DMARD
    • Drug: methotrexate
    • Drug: tocilizumab [RoActemra/Actemra]
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 11, 2015)
401
Original Estimated Enrollment  ICMJE
 (submitted: November 21, 2013)
420
Actual Study Completion Date  ICMJE March 2016
Actual Primary Completion Date July 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adult patients, >/= 18 years of age
  • Active rheumatoid arthritis (DAS28-ESR > 3.2), according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria of > 6 months duration
  • Patients with intolerance or inadequate response to methotrexate or other non-biologic DMRADs or inadequate response to a first ant-TNF agent
  • Oral corticosteroids (</= 10 mg/day prednisone or equivalent) 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-biologic DMRAD is allowed if at stable dose for at least 4 weeks prior to baseline
  • Females of childbearing potential and males with female partners of childbearing potential must be using a reliable means of contraception as defined by protocol during the study and for at least 3 months following the last dose of RoActemra/Actemra
  • Patients with intolerance or inadequate response to methotrexate or other non-biologic DMARDs or inadequate response to first anti-TNF agent

Exclusion Criteria:

  • Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following baseline
  • Rheumatic autoimmune disease other than RA or significant systemic involvement secondary to RA; secondary Sjögren's syndrome with RA is permitted
  • Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis
  • Diagnosis of juvenile idiopathic arthritis or juvenile RA and/or RA before the age of 16
  • Prior history of current inflammatory joint disease other than RA
  • Exposure to tocilizumab (either intravenous [IV] or SC) at any time prior to baseline
  • Treatment with any investigational agent with four weeks (or five-half lives of the investigational drug, whichever is longer) of screening
  • Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline
  • Previous treatment with Abatacept
  • History of severe allergic of anaphylactic reactions to human, humanized, or murine monoclonal antibodies
  • Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine, or gastrointestinal (GI) disease
  • History of diverticulitis, diverticulitis requiring antibiotic treatment, or chronic ulcerative lower GI disease such as Crohn's disease, ulcerative colitis, or other symptomatic lower GI conditions that might predispose to perforation
  • Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections (including but not limited to tuberculosis [TB] and atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections or nail beds)
  • Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of screening
  • Active TB requiring treatment within the previous 3 years
  • Positive hepatitis B or hepatitis C
  • Primary or secondary immunodeficiency (history of or currently active)
  • Evidence of active malignant disease, malignancies diagnosed with the previous 10 years (including hematological malignancies and solid tumors, except basal of squamous cell carcinoma of the skin diagnosed within the previous 20 years
  • Pregnant and lactating women
  • History of alcohol, drug, or chemical abuse within 1 year prior to screening
  • Neuropathies or other conditions that might interfere with pain evaluation
  • Inadequate hematological, real of liver function
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Ireland,   Portugal,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01995201
Other Study ID Numbers  ICMJE ML28709
2013-002429-52 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP