Rheumatoid ArthritisPhase 3NCT01988012
A Study of the Efficacy and Safety of Tocilizumab in Adults With Rheumatoid Arthritis.
A Phase 3 study testing tocilizumab in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 13 sites in Israel.
Trial summary
A multi-center, open-label single-arm study to evaluate the efficacy and safety of tocilizumab administered as a single, weekly injection in adults with rheumatoid arthritis. Combination therapy with methotrexate or other non-biologic disease modifying anti-rheumatic drugs (DMARDs) was permitted. 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?
- tocilizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 13 sitesIsrael
- Study dates
- Jan 2014to Jul 2015
- 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
- Adults >/= 18 years of age
- Diagnosis of active rheumatoid arthritis (RA) according to the revised (1987) American College of Rheumatology (ACR) criteria or European League Against Rheumatism (EULAR)/ACR (2010) criteria
- Previously treated with the following: three non-biologic DMARDs, and not treated with any biologic agent OR one biologic agent (alone or in combination with non-biologic DMARDs), and discontinued that agent for a reason
- Oral corticosteroids (</= 10 mg/day prednisone or equivalent), non-steroidal anti-inflammatory drug (NSAIDs) and non-biologic DMARDs are permitted if on a stable dose regimen for >/= 4 weeks prior to Baseline
- Use of effective contraception throughout the study as defined by protocol; female patients of childbearing potential must not be pregnant
Who cannot join
- Presence of serious, uncontrolled, clinically significant medical conditions
- History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower gastrointestinal (GI) disease that might predispose to perforation
- Current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections
- Any infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 4 weeks of Screening or oral antibiotics within 2 weeks of Screening
- Clinically significant findings on lab tests and/or hepatitis B or C, or human immunodeficiency virus (HIV) screenings
- Active tuberculosis (TB) requiring treatments within the previous 3 years
Show all 19Show fewer
- Evidence of active malignant disease, malignancies diagnosed within the previous 10 years, or breast cancer diagnosed within the previous 20 years
- History of alcohol, drug, or chemical abuse within 1 year prior to Screening
- Neuropathies or other conditions that might interfere with pain evaluation
- 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, including systemic lupus erythematosus, mixed connective tissue disorder, scleroderma, polymyositis, or significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis or Felty's syndrome). 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 IV or subcutaneous administration) at any time prior to Baseline
- Treatment with any investigational agent within 4 weeks (or five half-lives of the investigational drug, whichever is longer) of Screening
- Previous treatment with any cell-depleting therapies, including investigational agents approved therapies, with alkylating agents such as chlorambucil, or with total lymphoid irradiation
- Treatment with IV gamma globulin, plasmapheresis within 6 months of Baseline
- Immunization with a live/attenuated vaccine within 4 weeks prior to Baseline
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
Israel13 sites
Study site
Beer Yaacov, 6093000
Study site
Beersheba, 8410101
Study site
Haifa, 3109601
Study site
Haifa, 3339419
Study site
Haifa, 34362
Study site
Jerusalem, 9112001
Study site
Jerusalem, 91240
Study site
Kfar Saba, 44281
Study site
Petah Tikva, 4937211
Study site
Petah Tikva, 4941492
Study site
Ramat Gan, 5262000
Study site
Ramat Gan, 5262100
Study site
Tel Aviv, 6423906
About this study
Official title: An Open-label, Multicenter Study to Evaluate Disease Activity and Safety of Treatment With Actemra (Tocilizumab) Administered as Subcutaneous Injection in Adult RA Patients.
A multi-center, open-label single-arm study to evaluate the efficacy and safety of tocilizumab administered as a single, weekly injection in adults with rheumatoid arthritis. Combination therapy with methotrexate or other non-biologic disease modifying anti-rheumatic drugs (DMARDs) was permitted.
- Conditions
- Rheumatoid Arthritis
- Being tested
- tocilizumab
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tocilizumabBiological
Also called RoActemra/Actemra
162 milligram (mg) administered subcutaneously once weekly for 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| Tocilizumab | Experimental | Adults with rheumatoid arthritis will be treated with tocilizumab for 24 weeks followed by an 8 week follow-up period without treatment. Receives: Biological: tocilizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission and CDAI Low Disease Activity
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. Remission is defined as CDAI ≤2.8 and Low Disease Activity (LDA) is defined as 2.8< CDAI ≤10.
Measured: Week 24
Change From Baseline in CDAI
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: Baseline, Week 24
Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission and SDAI Low Disease Activity
Simplified Disease Activity Index (SDAI) was an index for measuring disease activity in RA and had a good correlation with the DAS28. The index was calculated using the following formula: SDAI: SJC28 + TJC28 + PGA (10 cm VAS) + PhGA (10 cm VAS + C-Reactive Protein (CRP) in milligram/liter (mg/L). VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. An SDAI score of ≤ 3.3 represents clinical remission, a score of ≤ 11.0 represents low disease activity.
Measured: Week 24
Change From Baseline in SDAI
Simplified Disease Activity Index (SDAI) was an index for measuring disease activity in RA and had a good correlation with the DAS28. The index was calculated using the following formula: SDAI: SJC28 + TJC28 + PGA (10 cm VAS) + PhGA (10 cm VAS + C-Reactive Protein (CRP) in mg/L. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. A negative change from baseline indicates an improvement.
Measured: Baseline, Week 24
Change From Baseline in Disease Activity Score 28-Erythrocyte-Sedimentation Rate (DAS28-ESR)
The DAS28-ESR score is a measure of the patient's disease activity calculated using the tender joint count on 28 joints (TJC28), swollen joint count on 28 joints (SJC28), patient's global assessment (PGA) of disease activity based on visual analog scale (VAS) and the erythrocyte sedimentation rate (ESR) in millimeter/hour (mm/hr). VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total possible score ranged from 0 to 10. Higher scores represent higher disease activity. A negative change from baseline indicates an improvement.
Measured: Baseline, Week 24
Percentage of Participants Achieving 20%, 50% and 70% Improvement in American College of Rheumatology (ACR) Response Scores (ACR20, ACR50 and ACR70)
An ACR20 response requires at least 20% improvement compared to baseline in SJC (based on 66 joints) and TJC (based on 68 joints) as well as at least 20% improvement in 3 of the following 5 assessments: 1) PGA pain VAS, 2) PGA VAS; 3) physician's global assessment of disease activity VAS, 4) Health Assessment Questionnaire-Disability Index (HAQ-DI) with 20 questions consisting of 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do; and 5) CRP in mg/L or ESR in mm/hr. ACR50 and ACR70 responses are defined in a similar way except that they required a 50% and 70% improvement from baseline, respectively. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity).
Measured: Week 24
Percentage of Participants With Good to Moderate European League Against Rheumatism (EULAR) Response
Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from the reference visit. Participants with a score lesser than or equal to (</=) 3.2 and reduction of greater than (>) 1.2 points were assessed as having a 'good' response. Participants with a score >3.2 with reduction of >1.2 points, or a score <=5.1 with reduction of >0.6 to <=1.2 points, were assessed as having a 'moderate' response. Participants with a score >5.1 with reduction of >0.6 to <=1.2 points, or any score with reduction <=0.6 points, were assessed as non-responders with response recorded as 'none.'
Measured: Week 24
Change From Baseline in TJC and SJC
The number of tender joints (based on 68 joints) and swollen joints (based on 66 joints) were counted at each visit. TJC was determined by identifying the joints that were painful under pressure or to passive motion; no tenderness =0, tenderness =1. SJC was determined by identifying swelling; no swelling =0, swelling =1. A negative change from baseline indicates an improvement.
Measured: Baseline, Week 24
Change From Baseline in Percentage of Participants on Tocilizumab Monotherapy
Participants were either on tocilizumab monotherapy or tocilizumab plus non-biologic disease modifying anti-rheumatic drugs (DMARDs). Reported here is the percentage of participants on tocilizumab monotherapy at baseline and the change from baseline at Week 24. A positive change from baseline at Week 24 indicates the percentage of participants, who discontinued DMARDs during the study.
Measured: Baseline, Week 24
Change From Baseline in Patient Global Assessment of Disease Activity Visual Analog Scale (PGA VAS)
PGA VAS represents the participant's overall assessment of their current disease activity on a 100 millimeter (mm) horizontal VAS scale from 0 (no disease activity) to 100 (maximum disease activity). A negative change from baseline indicates an improvement.
Measured: Baseline, Week 24
Change From Baseline in Patient Pain VAS
Patient Pain VAS represents the participant's assessment of his/her current level of pain on a 100 mm horizontal VAS scale from 0 (no disease activity) to 100 (maximum disease activity). A negative change from baseline indicates an improvement.
Measured: Baseline, Week 24
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI)
The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities and 20 questions. Each category contains multiple questions, which were answered using a 4-point scale from 0 (without any difficulty) to 3 (unable to do). The overall index score was an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. A negative change from baseline indicates an improvement.
Measured: Baseline, Week 24
Change From Baseline in Patient Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
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 52. The figures are reversed during score calculations, so that higher score values indicate more favorable conditions. A positive change from baseline indicates an improvement.
Measured: Baseline, Week 24
Total Scores on Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Scale (HAS)
The HDRS is a clinician-administered depression assessment and consists of 17 items with a total score range from 0 to 54. A higher score indicates a worse outcome. HAS is a clinician-administered assessment to measure the severity of anxiety symptoms and consists of 14 items with a total score range from 0 to 56. A higher score indicates a worse outcome.
Measured: Baseline, Week 24
Secondary outcomes (5)
Percentage of Participants With Adverse Events (AEs) and AEs of Special Interest (AESIs)
An AE is any untoward medical occurrence in a participant administered a drug and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug, whether or not considered related to the drug. Preexisting conditions which worsen during a study are also considered as AEs. AESIs are AEs that occur in categories of special interest with regard to the benefit-risk profile and overall safety of a drug. The following nine categories of AESIs were identified for tocilizumab: 1) serious and/or medically significant infections, 2) myocardial infarction/acute coronary syndrome, 3) gastrointestinal perforations, 4) malignancies, 5) anaphylaxis/hypersensitivity reactions, 6) demyelinating disorders, 7) stroke, 8) serious and/or medically significant bleeding events, and 9) serious and/or medically significant hepatic events.
Measured: Up to Follow-up Week 32
Percentage of Participants Who Required Dose Modifications or Discontinued Study Due to AEs
Measured: Up to Week 24
Immunogenicity: Percentage of Participants With Anti-tocilizumab Antibodies
Reported is the percentage of participants positive for anti-tocilizumab antibodies in the confirmatory anti-tocilizumab antibody assay, which followed an initial anti-tocilizumab screen. Participants, who withdrew from the study
Measured: Baseline, Week 24, Follow-up Week 32 and Early Withdrawal
Immunogenicity: Tocilizumab Levels
Measured: Week 12, Week 24, Follow-up Week 32 and Early Withdrawal
Immunogenicity: Change From Week 1 in Soluble Interleukin-6 Receptor (sIL-6R) Levels
A positive change from Week 1 indicates an increase in sIL-6R levels.
Measured: Week 1, Week 12, Week 24, Follow-up Week 32 and Early Withdrawal
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2013 (estimated)
- Study startJan 2014
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01988012
- Sponsor's protocol ID
- ML28698
- Status last verified
- Jan 2017
- First submitted
- 31 Oct 2013
- Last updated
- 6 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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 30649524Choy 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
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multicenter Study to Evaluate Disease Activity and Safety of Treatment With Actemra (Tocilizumab) Administered as Subcutaneous Injection in Adult RA Patients.
- ClinicalTrials.gov ID
- NCT01988012
- Acronym / sponsor ID
- ML28698
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- Jan 2014
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 20 Nov 2013 (estimated)
- Results
- Posted 6 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A multi-center, open-label single-arm study to evaluate the efficacy and safety of tocilizumab administered as a single, weekly injection in adults with rheumatoid arthritis. Combination therapy with methotrexate or other non-biologic disease modifying anti-rheumatic drugs (DMARDs) was permitted.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tocilizumab | Experimental | Biological: tocilizumabAdults with rheumatoid arthritis will be treated with tocilizumab for 24 weeks followed by an 8 week follow-up period without treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adults >/= 18 years of age
- Diagnosis of active rheumatoid arthritis (RA) according to the revised (1987) American College of Rheumatology (ACR) criteria or European League Against Rheumatism (EULAR)/ACR (2010) criteria
- Previously treated with the following: three non-biologic DMARDs, and not treated with any biologic agent OR one biologic agent (alone or in combination with non-biologic DMARDs), and discontinued that agent for a reason
- Oral corticosteroids (</= 10 mg/day prednisone or equivalent), non-steroidal anti-inflammatory drug (NSAIDs) and non-biologic DMARDs are permitted if on a stable dose regimen for >/= 4 weeks prior to Baseline
- Use of effective contraception throughout the study as defined by protocol; female patients of childbearing potential must not be pregnant
Key exclusion criteria (19 listed)
- Presence of serious, uncontrolled, clinically significant medical conditions
- History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower gastrointestinal (GI) disease that might predispose to perforation
- Current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections
- Any infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 4 weeks of Screening or oral antibiotics within 2 weeks of Screening
- Clinically significant findings on lab tests and/or hepatitis B or C, or human immunodeficiency virus (HIV) screenings
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| tocilizumabAlso: RoActemra/Actemra162 milligram (mg) administered subcutaneously once weekly for 24 weeks | Biological | Tocilizumab |
Primary outcome
Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission and CDAI Low Disease Activity
Time frame: 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. Remission is defined as CDAI ≤2.8 and Low Disease Activity (LDA) is defined as 2.8< CDAI ≤10.
Change From Baseline in CDAI
Time frame: Baseline, 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 Participants With Simplified Disease Activity Index (SDAI) Remission and SDAI Low Disease Activity
Time frame: Week 24
Simplified Disease Activity Index (SDAI) was an index for measuring disease activity in RA and had a good correlation with the DAS28. The index was calculated using the following formula: SDAI: SJC28 + TJC28 + PGA (10 cm VAS) + PhGA (10 cm VAS + C-Reactive Protein (CRP) in milligram/liter (mg/L). VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. An SDAI score of ≤ 3.3 represents clinical remission, a score of ≤ 11.0 represents low disease activity.
Change From Baseline in SDAI
Time frame: Baseline, Week 24
Simplified Disease Activity Index (SDAI) was an index for measuring disease activity in RA and had a good correlation with the DAS28. The index was calculated using the following formula: SDAI: SJC28 + TJC28 + PGA (10 cm VAS) + PhGA (10 cm VAS + C-Reactive Protein (CRP) in mg/L. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. A negative change from baseline indicates an improvement.
Change From Baseline in Disease Activity Score 28-Erythrocyte-Sedimentation Rate (DAS28-ESR)
Time frame: Baseline, Week 24
The DAS28-ESR score is a measure of the patient's disease activity calculated using the tender joint count on 28 joints (TJC28), swollen joint count on 28 joints (SJC28), patient's global assessment (PGA) of disease activity based on visual analog scale (VAS) and the erythrocyte sedimentation rate (ESR) in millimeter/hour (mm/hr). VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total possible score ranged from 0 to 10. Higher scores represent higher disease activity. A negative change from baseline indicates an improvement.
Percentage of Participants Achieving 20%, 50% and 70% Improvement in American College of Rheumatology (ACR) Response Scores (ACR20, ACR50 and ACR70)
Time frame: Week 24
An ACR20 response requires at least 20% improvement compared to baseline in SJC (based on 66 joints) and TJC (based on 68 joints) as well as at least 20% improvement in 3 of the following 5 assessments: 1) PGA pain VAS, 2) PGA VAS; 3) physician's global assessment of disease activity VAS, 4) Health Assessment Questionnaire-Disability Index (HAQ-DI) with 20 questions consisting of 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do; and 5) CRP in mg/L or ESR in mm/hr. ACR50 and ACR70 responses are defined in a similar way except that they required a 50% and 70% improvement from baseline, respectively. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity).
Percentage of Participants With Good to Moderate European League Against Rheumatism (EULAR) Response
Time frame: Week 24
Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from the reference visit. Participants with a score lesser than or equal to (</=) 3.2 and reduction of greater than (>) 1.2 points were assessed as having a 'good' response. Participants with a score >3.2 with reduction of >1.2 points, or a score <=5.1 with reduction of >0.6 to <=1.2 points, were assessed as having a 'moderate' response. Participants with a score >5.1 with reduction of >0.6 to <=1.2 points, or any score with reduction <=0.6 points, were assessed as non-responders with response recorded as 'none.'
Change From Baseline in TJC and SJC
Time frame: Baseline, Week 24
The number of tender joints (based on 68 joints) and swollen joints (based on 66 joints) were counted at each visit. TJC was determined by identifying the joints that were painful under pressure or to passive motion; no tenderness =0, tenderness =1. SJC was determined by identifying swelling; no swelling =0, swelling =1. A negative change from baseline indicates an improvement.
Change From Baseline in Percentage of Participants on Tocilizumab Monotherapy
Time frame: Baseline, Week 24
Participants were either on tocilizumab monotherapy or tocilizumab plus non-biologic disease modifying anti-rheumatic drugs (DMARDs). Reported here is the percentage of participants on tocilizumab monotherapy at baseline and the change from baseline at Week 24. A positive change from baseline at Week 24 indicates the percentage of participants, who discontinued DMARDs during the study.
Change From Baseline in Patient Global Assessment of Disease Activity Visual Analog Scale (PGA VAS)
Time frame: Baseline, Week 24
PGA VAS represents the participant's overall assessment of their current disease activity on a 100 millimeter (mm) horizontal VAS scale from 0 (no disease activity) to 100 (maximum disease activity). A negative change from baseline indicates an improvement.
Change From Baseline in Patient Pain VAS
Time frame: Baseline, Week 24
Patient Pain VAS represents the participant's assessment of his/her current level of pain on a 100 mm horizontal VAS scale from 0 (no disease activity) to 100 (maximum disease activity). A negative change from baseline indicates an improvement.
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI)
Time frame: Baseline, Week 24
The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities and 20 questions. Each category contains multiple questions, which were answered using a 4-point scale from 0 (without any difficulty) to 3 (unable to do). The overall index score was an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. A negative change from baseline indicates an improvement.
Change From Baseline in Patient Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
Time frame: Baseline, 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 52. The figures are reversed during score calculations, so that higher score values indicate more favorable conditions. A positive change from baseline indicates an improvement.
Total Scores on Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Scale (HAS)
Time frame: Baseline, Week 24
The HDRS is a clinician-administered depression assessment and consists of 17 items with a total score range from 0 to 54. A higher score indicates a worse outcome. HAS is a clinician-administered assessment to measure the severity of anxiety symptoms and consists of 14 items with a total score range from 0 to 56. A higher score indicates a worse outcome.
5 secondary outcomes
Percentage of Participants With Adverse Events (AEs) and AEs of Special Interest (AESIs)
Time frame: Up to Follow-up Week 32
Percentage of Participants Who Required Dose Modifications or Discontinued Study Due to AEs
Time frame: Up to Week 24
Immunogenicity: Percentage of Participants With Anti-tocilizumab Antibodies
Time frame: Baseline, Week 24, Follow-up Week 32 and Early Withdrawal
Immunogenicity: Tocilizumab Levels
Time frame: Week 12, Week 24, Follow-up Week 32 and Early Withdrawal
Immunogenicity: Change From Week 1 in Soluble Interleukin-6 Receptor (sIL-6R) Levels
Time frame: Week 1, Week 12, Week 24, Follow-up Week 32 and Early Withdrawal
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30649524Choy 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.
- Derived from this study: PubMed 29244149Choy 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing tocilizumab in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 13 sites in Israel.
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 5 inclusion and 19 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 6 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Israel. 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 6 Mar 2017). 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 With Clinical Disease Activity Index (CDAI) Remission and CDAI Low Disease Activity (time frame: Week 24). The study lists 14 primary outcomes in all. 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 NCT01988012, which also lists 2 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 6 Mar 2017.