AzTrials
AzTrials

Rheumatoid ArthritisPhase 3NCT01995201

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

A Phase 3 study testing DMARD, methotrexate and tocilizumab [RoActemra/Actemra] in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 53 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Rheumatoid Arthritis
What is being tested?
DMARD, methotrexate and tocilizumab [RoActemra/Actemra]
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
401 participants
Where
53 sitesin 3 countries
Study dates
Sep 2013to Mar 2016
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

53 sites in 3 countries.

53 sites in 3 countries

Spain41 sites

  • Study site

    A Coruña, La Coruña, 15006

  • Study site

    Alicante, 03010

  • Study site

    Barcelona, 08025

  • Study site

    Barcelona, 08036

  • Study site

    Bilbao, Vizcaya, 48013

  • Study site

    Burgos, 06006

  • Study site

    Cartagena, Murcia, 30203

  • Study site

    Córdoba, 14004

  • Study site

    Donostia / San Sebastian, Guipuzcoa, 20080

  • Study site

    El Palmar, Murcia, 30120

  • Study site

    Elche, Alicante, 03203

  • Study site

    Fuenlabrada, Madrid, 28942

  • Study site

    Granada, 18014

  • Study site

    Guadalajara, 19002

  • Study site

    Jerez de la Frontera, Cadiz, 11407

  • Study site

    Las Palmas de Gran Canaria, Las Palmas, 35016

  • Study site

    Madrid, 28006

  • Study site

    Madrid, 28007

  • Study site

    Madrid, 28034

  • Study site

    Madrid, 28041

  • Study site

    Madrid, 28046

  • Study site

    Madrid, 28222

  • Study site

    Madrid, 28905

  • Study site

    Málaga, 29009

  • Study site

    Mérida, Badajoz, 06800

  • Study site

    Palma de Mallorca, Balearic Islands, 07198

  • Study site

    Sabadell, Barcelona, 08208

  • Study site

    Salamanca, 37007

  • Study site

    Sant Joan Despí, Barcelona, 08970

  • Study site

    Santa Cruz de Tenerife, Tenerife, 38010

  • Study site

    Santiago de Compostela, La Coruña, 15706

  • Study site

    Seville, 41009

  • Study site

    Seville, 41010

  • Study site

    Seville, 41013

  • Study site

    Tarragona, 43700

  • Study site

    Terrassa, Barcelona, 08221

  • Study site

    Toledo, 45004

  • Study site

    Torrelavega, Cantabria, 39300

  • Study site

    Valencia, 46010

  • Study site

    Valenica, Valencia, 46009

  • Study site

    Zaragoza, 50009

Other trials in Spain

Ireland6 sites

  • Study site

    Co Leitrim

  • Study site

    Cork

  • Study site

    Dublin, 24

  • Study site

    Dublin, 4

  • Study site

    Limerick, 0

  • Study site

    Waterford

Other trials in Ireland

Portugal6 sites

  • Study site

    Almada, 2801-951

  • Study site

    Amadora, 3814-501

  • Study site

    Lisbon, 1050-34

  • Study site

    Lisbon, 1649-035

  • Study site

    Porto, 4099-001

  • Study site

    Porto, 4200-319

Other trials in Portugal

About this study

Official title: 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

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.

Being tested
DMARD, methotrexate, tocilizumab [RoActemra/Actemra]
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DMARDDrug

    non-biological disease-modifying antirheumatic drugs at stable dose

  • methotrexateDrug

    stable dose

  • tocilizumab [RoActemra/Actemra]Drug

    162 mg subcutaneously (SC) qw, Weeks 1-24

  • tocilizumab [RoActemra/Actemra]Drug

    162 mg SC qw or q2w, Weeks 24-48

  • tocilizumab [RoActemra/Actemra]Drug

    162 mg SC qw, Weeks 24-48

Study groups in NCT01995201
Study groupRoleWhat they receive
Part 1: All patientsExperimentalNot described
Receives: Drug: DMARD; Drug: methotrexate; Drug: tocilizumab [RoActemra/Actemra]
Part 2 A: Sustained clinical remissionExperimentalNot described
Receives: Drug: DMARD; Drug: methotrexate; Drug: tocilizumab [RoActemra/Actemra]
Part 2 B: Low disease activityExperimentalNot described
Receives: Drug: DMARD; Drug: methotrexate; Drug: tocilizumab [RoActemra/Actemra]

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    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.

    Measured: Week 20 and Week 24

Secondary outcomes (42)

  1. Mean Change in Disease Activity Score 28 - Erythrocyte Sedimentation Rate(DAS28-ESR)

    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.

    Measured: From week 24 up to week 48

  2. Percentage of Patients Allocated in Groups A1 and A2 Who Remain With Clinical Remission Activity (DAS 28 ESR <2.6) 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.

    Measured: From week 28 up to week 48

  3. Percentage of Patients Reporting Change in DAS 28 ESR >1.2 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 will be used to calculate the DAS28 score.

    Measured: From week 28 up to week 48

  4. Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores 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]).

    Measured: From week 2 until week 24

  5. Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores 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]).

    Measured: From week 28 until week 48

  6. Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to 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.

    Measured: From week 2 until week 24

  7. Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to 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.

    Measured: From week 28 until week 48

  8. Mean Change in Clinical Disease Activity Index (CDAI) From Baseline up 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.

    Measured: From baseline to Week 24

  9. Mean Change From Baseline in Clinical Disease Activity Index (CDAI) up to 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.

    Measured: From week 24 until week 48

  10. Mean Change in Simplified Disease Activity Index (SDAI) From Baseline up 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.

    Measured: From baseline to Week 24

  11. Mean Change in Simplified Disease Activity Index (SDAI) From Week 24 up to 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.

    Measured: From week 24 until week 48

  12. Mean Change From Baseline in Total Tender Joint Counts (TJC) Until 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.

    Measured: From baseline to Week 24

  13. Mean Change From Baseline in Total Tender Joint Counts (TJC) 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.

    Measured: From week 24 until week 48

  14. Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until 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.

    Measured: From baseline to Week 24

  15. Mean Change in Total Swollen Joint Counts (SJC) From Baseline 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.

    Measured: From week 24 until week 48

  16. Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) 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.

    Measured: Week 48

  17. Percentages of Patients With Remission (CDAI<2.8) Until 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.

    Measured: From baseline to Week 24

  18. Percentages of Patients With Remission (CDAI<2.8) 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.

    Measured: From week 28 until week 48

  19. Percentages of Patients With Remission (SDAI<3.3) Until 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.

    Measured: From baseline to Week 24

  20. Percentages of Patients With Remission (SDAI<3.3) 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.

    Measured: From week 28 until week 48

  21. Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up 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.

    Measured: From baseline to Week 24

  22. Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) 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 was used to calculate the DAS28 score.

    Measured: From week 28 until week 48

  23. Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until 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.

    Measured: From baseline to Week 24

  24. Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) 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.

    Measured: From week 28 until week 48

  25. Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until 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.

    Measured: From baseline to Week 24

  26. Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) 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.

    Measured: From week 28 until week 48

  27. Safety: Number of Patients Reporting Adverse Events up 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

    Measured: From baseline to Week 24

  28. Safety: Number of Patients Reporting Adverse Events up to 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

    Measured: From week 24 until week 48

  29. Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 24

    Number of patients resulting positive to anti-tocilizumab antibodies test are reported.

    Measured: From baseline to Week 24

  30. Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 48

    Number of patients resulting positive to anti-tocilizumab antibodies test are reported.

    Measured: From week 24 until week 48

  31. Immunogenicity: TCZ Levels up to Week 24

    Mean concentrations of TCZ in patients' blood are reported.

    Measured: From baseline to Week 24

  32. Immunogenicity: TCZ Levels at Week 36 and Early Withdrawal Visit

    Mean concentrations of TCZ in patients' blood are reported.

    Measured: week 36 and early withdrawal visit

  33. Immunogenicity: SIL-6R Levels up to Week 24

    Mean concentration of SIL-6R in patients' blood are reported.

    Measured: From baseline to Week 24

  34. Immunogenicity: SIL-6R Levels at Week 36 and Early Withdrawal Visit

    Mean concentration of SIL-6R in patients' blood are reported.

    Measured: Baseline, Week 36 and Early Withdrawal Visit

  35. Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up 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.

    Measured: From baseline to Week 24

  36. Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to 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.

    Measured: Baseline, from week 28 until week 48

  37. Assessment of Pain Reported by the Patient (VAS) Until 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".

    Measured: From baseline to Week 24

  38. Assessment of Pain Reported by the Patient (VAS) 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".

    Measured: Baseline, from week 28 until week 48

  39. Health Assessment Questionnaire-Disability Index (HAQ-DI) up 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.

    Measured: From baseline to Week 24

  40. Health Assessment Questionnaire-Disability Index (HAQ-DI) up to 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.

    Measured: Baseline, from week 28 until week 48

  41. Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up 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.

    Measured: From baseline to Week 24

  42. Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to 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.

    Measured: Baseline, from week 28 until week 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Nov 2013 (estimated)
  2. Study startSep 2013
  3. Primary completionJul 2015
  4. Study completionMar 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
401 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01995201
Sponsor's protocol ID
ML28709
Other IDs
2013-002429-52
Status last verified
Jun 2017
First submitted
1 Nov 2013
Last updated
26 Jan 2018

Publications

  • Sanmarti R, Veale DJ, Martin-Mola E, Escudero-Contreras A, Gonzalez C, Ercole L, Alonso R, Fonseca JE; ToSpace Study Group. Reducing or Maintaining the Dose of Subcutaneous Tocilizumab in Patients With Rheumatoid Arthritis in Clinical Remission: A Randomized, Open-Label Trial. Arthritis Rheumatol. 2019 Oct;71(10):1616-1625. doi: 10.1002/art.40905. Epub 2019 Sep 24.

    PubMed 31087542

  • Choy E, Caporali R, Xavier R, Fautrel B, Sanmarti R, Bao M, Devenport J, Petho-Schramm A. Effects of concomitant glucocorticoids in TOZURA, a common-framework study programme of subcutaneous tocilizumab in rheumatoid arthritis. Rheumatology (Oxford). 2019 Jun 1;58(6):1056-1064. doi: 10.1093/rheumatology/key393.

    PubMed 30649524

  • Choy E, Caporali R, Xavier R, Fautrel B, Sanmarti R, Bao M, Bernasconi C, Petho-Schramm A. Subcutaneous tocilizumab in rheumatoid arthritis: findings from the common-framework phase 4 study programme TOZURA conducted in 22 countries. Rheumatology (Oxford). 2018 Mar 1;57(3):499-507. doi: 10.1093/rheumatology/kex443.

    PubMed 29244149

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing DMARD, methotrexate and tocilizumab [RoActemra/Actemra] in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 53 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 53 sites in Spain, Ireland, Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01995201, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2018.

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