Rheumatoid ArthritisPhase 2NCT00845832
A Study of Combination Treatment With MabThera (Rituximab) and RoActemra (Tocilizumab) Versus RoActemra in Patients With Rheumatoid Arthritis With an Incomplete Response to Methotrexate
A Phase 2 study testing rituximab [MabThera/Rituxan] and tocilizumab [RoActemra/Actemra] in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 24 sites in 8 countries.
Trial summary
This 2 part study will investigate the safety, tolerability and efficacy of MabT hera in combination with RoActemra in patients with active rheumatoid arthritis despite a stable dose of methotrexate. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- rituximab [MabThera/Rituxan] and tocilizumab [RoActemra/Actemra]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 24 sitesin 8 countries
- Study dates
- Mar 2009to Mar 2013
- Phase
- Phase 2
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- adult patients, 18-65 years of age;
- rheumatoid arthritis, functional status I-III;
- SJC>=4 (28 joint count) and TJC>=4 (28 joint count) at screening and baseline;
- RF and/or anti-CCP positive;
- may have failed up to 1 approved anti-TNF agent (infliximab, etanercept or adalimumab);
- inadequate response to methotrexate, at a dose of 7.5-25mg weekly for at least 12 weeks, at a stable dose for past 4 weeks.
Who cannot join
- rheumatic autoimmune disease other than rheumatoid arthritis, or significant systemic involvement secondary to rheumatoid arthritis;
- history of, or current, inflammatory joint disease other than rheumatoid arthritis;
- diagnosis of juvenile idiopathic arthritis and/or rheumatoid arthritis before age 16;
- significant cardiac or pulmonary disease;
- previous treatment with any biologic agent for rheumatoid arthritis (other than infliximab, etanercept or adalimumab).
Trial locations and contacts
24 sites in 8 countries.
24 sites in 8 countries
Germany5 sites
Study site
Berlin, 10117
Study site
Berlin, 14059
Study site
Cologne, 50924
Study site
Heidelberg, 69120
Study site
Würzburg, 97080
France4 sites
Study site
Le Kremlin-Bicêtre, 94275
Study site
Montpellier, 34295
Study site
Paris, 75679
Study site
Strasbourg, 67098
Spain4 sites
Study site
Madrid, Madrid, 28007
Study site
Santander, Cantabria, 39008
Study site
Santiago de Compostela, La Coruña, 15706
Study site
Seville, Sevilla, 41009
Poland3 sites
Study site
Bytom, 41-902
Study site
Lublin, 20-607
Study site
Poznan, 60-218
Netherlands2 sites
Study site
Amsterdam, 1105 AZ
Study site
Leiden, 2333 ZA
United Kingdom2 sites
Study site
Newcastle upon Tyne, NE1 4LP
Study site
Southampton, SO16 6YD
About this study
Official title: A Randomized, Active Controlled, Double-blind, Study to Compare the Safety and Reduction in Disease Activity With the Combination of Rituximab (MabThera®)and Tocilizumab (RoActemra®) Versus Tocilizumab in Patients With Active Rheumatoid Arthritis With an Incomplete Response to Methotrexate
This 2 part study will investigate the safety, tolerability and efficacy of MabT hera in combination with RoActemra in patients with active rheumatoid arthritis despite a stable dose of methotrexate. In Part 1 of the study, patients will be randomized to receive either MabThera 0.5g iv or placebo on days 1 and 15, follo wed by RoActemra at one of the ascending doses between 2mg/kg and 8mg/kg at week s 4, 8 and 12 (MabThera arm) or 8mg/kg (placebo arm). In Part 2, additional pati ents will be randomized to one of 2 groups to receive MabThera 0.5g on days 1 an d 15 followed by the selected dose (from Part 1)of RoActemra at weeks 4, 8 and 1 2, or placebo on days 1 and 15 followed by RoActemra 8mg/kg at weeks 4,8 and 12.
All patients will then be eligible to receive extension treatment withRoActemra every 4 weeks. The anticipated time on study treatment is 12 months, and the tar get sample size is <100 individuals.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Placebo, rituximab [MabThera/Rituxan], 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.
PlaceboDrug
iv on days 1 and 15 (Parts 1 and 2)
rituximab [MabThera/Rituxan]Drug
0.5g iv on days 1 and 15 (Parts 1 and 2)
tocilizumab [RoActemra/Actemra]Drug
2mg/kg-8mg/kg iv in Part 1 and selected dose in Part 2, on weeks 4, 8 and 12---Arm 1\n8mg/kg iv on weeks 4,8 and 12 (Parts 1 and 2)--- Arm 2
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: rituximab [MabThera/Rituxan]; Drug: tocilizumab [RoActemra/Actemra] |
| 2 | Active comparator | Not described Receives: Drug: Placebo; Drug: tocilizumab [RoActemra/Actemra] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Achieving Low Disease Activity (LDA) at Week 16 Assessed Using Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR)
The Disease Activity Score based on 28 joint count (DAS28) and Erythrocyte Sedimentation Rate (ESR), is a measure of the participant's disease activity. It is based on the Tender Joint Count (TJC [28 joints]), Swollen Joint Count (SJC [28 joints]), participant's global assessment of disease activity (PtGA) Visual Analog Scale (VAS) in millimeters (mm), and ESR in millimeters per hour (mm/hour). DAS28-ESR scores range from 0 - 10. Definition of LDA was based on DAS28-ESR scores. To achieve LDA the DAS28-ESR had to be (less than or equal to) ≤ 3.2.
DAS28-ESR equals (=) (0.56 times (*) (square root)√ TJC plus (+) (0.28 * √ SJC + (0.70 * ln(ESR))+(0.014 * (Global Health) GH)
Where:
TJC = based on 28 joints SJC = based on 28 joints ESR = erythrocyte sedimentation rate in mm/hour GH = participant's global assessment of disease activity ln = natural log
Measured: Week 16
Secondary outcomes (12)
Percentage of Participants Achieving Remission at Week 16 Assessed Using DAS28-ESR
The DAS28-ESR score is a measure of the participant's disease activity. It is based on the TJC (28 joints), SJC (28 joints), participant's global assessment of disease activity (mm), and ESR (mm/hour). DAS28-ESR is expressed on a unit on a scale with the minimum score=0 (best) to maximum score=10 (worst). Remission was defined as DAS28-ESR less than (<) 2.6
Measured: Week 16
Percentage of Participants by European League Against Rheumatism (EULAR) Response Category at Week 16
DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline (greater than) >1.2 with DAS28 ≤3.2; moderate responders: change from baseline >1.2 with DAS28 >3.2 to ≤5.1 or DAS28-ESR >5.1 or change from baseline >0.6 to ≤1.2 with DAS28 ≤5.1; nonresponders: change from baseline ≤0.6 or change from baseline >0.6 and ≤1.2 with DAS28 >5.1.
Measured: Week 16
Change From Baseline in DAS28-ESR
The DAS28-ESR score is a measure of the participant's disease activity. It is based on the TJC (28 joints), SJC (28 joints), participant's global assessment of disease activity (mm), and ESR (mm/hour). DAS28-ESR is expressed as a score on a scale with the minimum score=0 (best) to maximum score=10 (worst).
DAS28-ESR scores were calculated as follows: DAS28-ESR = (0.56 * √TJC)+(0.28 * √SJC)+(0.70 * ln(ESR))+(0.014 * GH).
No imputation used for tender and swollen joint counts, ESR, and patient's global assessment of disease activity VAS.
Measured: Weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48
Clinical Disease Activity Index Scores
The Clinical Disease Activity Index (CDAI) score was calculated according to the following formula: CDAI = SJC + TJC + GH/10 + EGA/10
Where:
SJC = swollen joint count based on 28 joints; TJC = tender joint count based on 28 joints; GH = Participant's global assessment of disease activity; EGA = evaluator's (physician's) global assessment of disease activity. CDAI scores range from 0-76 and the following cut-off points for different disease activity states have been used: high disease activity >22; moderate disease activity >10 and ≤22; LDA >2.8 and ≤10; and remission ≤ 2.8. No imputation used for TJC, SJC, Patient's Global Assessment of Disease Activity VAS and Physicians global assessment of disease activity VAS.
Measured: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48
Simplified Disease Activity Index (SDAI) Scores
The SDAI is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), Participant and Physician assessed global disease activity (assessed on 0-100 mm VAS; higher scores = greater affection due to disease activity), and ESR (mm/hour). SDAI total score ranged from 0 to 86. Higher scores indicated greater disease activity.
Measured: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40, and 48
Change From Baseline to Week 48 in SJC and TJC
An assessment of 28 joints for swelling and tenderness will be made. Joints will be assessed and classified as swollen (1)/not swollen (0) and tender(1)/not tender (0) by pressure and joint manipulation on physical examination. Joint prosthesis, arthrodesis or fused joints were not taken into consideration for swelling or tenderness. The 28 joints assessed comprise shoulders (2 joints), elbows (2 joints), wrists (2 joints), metacarpophalangeal joints on digits 1-5 (10 joints), interphalangeal on digit 1 (2 joints), proximal interphalangeal joints on digits 2-5 (8 joints), and knees (2 joints).
Measured: Baseline and Week 48
Change From Baseline to Week 48 in Health Assessment Questionnaire (HAQ)
The Stanford Health Assessment Questionnaire disability index specific for rheumatoid arthritis was completed by the participants for efficacy assessments.
Measured: Baseline and Week 48
Change From Baseline to Week 48 in C-Reactive Protein (CRP)
CRP is an acute phase reactant and is a measure of inflammation.
Measured: Baseline and Week 48
Change From Baseline to Week 48 in ESR
ESR is an acute phase reactant and is a measure of inflammation.
Measured: Baseline and Week 48
Change From Baseline to Week 48 in Physician's Global Assessment of Disease Activity
Physician Global Assessment of Disease Activity was measured on a 0 to 100 mm VAS, with 0 mm = no disease activity and 100 mm= maximum disease activity. The physician marked the line according to their assessment and the distance from the left edge was measured.
Measured: Baseline and Week 48
Change From Baseline to Week 48 in Participant's Global Assessment of Disease Activity
Participant's Global Assessment of Disease Activity was measured on a 0 to 100 mm VAS, with 0 mm = no disease activity and 100 mm = maximum disease activity. The participant marked the line according to their assessment and the distance from the left edge was measured.
Measured: Baseline and Week 48
Change From Baseline to Week 48 in Participant's Assessment of Pain
Participant's Global Assessment of Disease Activity was measured on a 0 to 100 mm VAS, with 0 mm = no pain and 100 mm = maximum pain. The participant marked the line according to their assessment and the distance from the left edge was measured.
Measured: Baseline and Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2009 (estimated)
- Study startMar 2009
- Primary completionMar 2013
- Study completionMar 2013
Why it stopped: The study was terminated early because of a related decision to stop the development of ocrelizumab in rheumatoid arthritis.
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.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 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
- NCT00845832
- Sponsor's protocol ID
- WX21956
- Other IDs
- 2008-005525-11, 2008
- Status last verified
- Dec 2014
- First submitted
- 17 Feb 2009
- Last updated
- 24 Dec 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Active Controlled, Double-blind, Study to Compare the Safety and Reduction in Disease Activity With the Combination of Rituximab (MabThera®)and Tocilizumab (RoActemra®) Versus Tocilizumab in Patients With Active Rheumatoid Arthritis With an Incomplete Response to Methotrexate
- ClinicalTrials.gov ID
- NCT00845832
- Acronym / sponsor ID
- WX21956
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated early because of a related decision to stop the development of ocrelizumab in rheumatoid arthritis.
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- Mar 2009
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 18 Feb 2009 (estimated)
- Results
- Posted 24 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This 2 part study will investigate the safety, tolerability and efficacy of MabT hera in combination with RoActemra in patients with active rheumatoid arthritis despite a stable dose of methotrexate. In Part 1 of the study, patients will be randomized to receive either MabThera 0.5g iv or placebo on days 1 and 15, follo wed by RoActemra at one of the ascending doses between 2mg/kg and 8mg/kg at week s 4, 8 and 12 (MabThera arm) or 8mg/kg (placebo arm). In Part 2, additional pati ents will be randomized to one of 2 groups to receive MabThera 0.5g on days 1 an d 15 followed by the selected dose (from Part 1)of RoActemra at weeks 4, 8 and 1 2, or placebo on days 1 and 15 followed by RoActemra 8mg/kg at weeks 4,8 and 12.
All patients will then be eligible to receive extension treatment withRoActemra every 4 weeks. The anticipated time on study treatment is 12 months, and the tar get sample size is <100 individuals.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: rituximab [MabThera/Rituxan], Drug: tocilizumab [RoActemra/Actemra] |
| 2 | Active comparator | Drug: Placebo, Drug: tocilizumab [RoActemra/Actemra] |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- adult patients, 18-65 years of age;
- rheumatoid arthritis, functional status I-III;
- SJC>=4 (28 joint count) and TJC>=4 (28 joint count) at screening and baseline;
- RF and/or anti-CCP positive;
- may have failed up to 1 approved anti-TNF agent (infliximab, etanercept or adalimumab);
Key exclusion criteria (5 listed)
- rheumatic autoimmune disease other than rheumatoid arthritis, or significant systemic involvement secondary to rheumatoid arthritis;
- history of, or current, inflammatory joint disease other than rheumatoid arthritis;
- diagnosis of juvenile idiopathic arthritis and/or rheumatoid arthritis before age 16;
- significant cardiac or pulmonary disease;
- previous treatment with any biologic agent for rheumatoid arthritis (other than infliximab, etanercept or adalimumab).
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 |
|---|---|---|
| Placeboiv on days 1 and 15 (Parts 1 and 2) | Drug | 2 |
| rituximab [MabThera/Rituxan]0.5g iv on days 1 and 15 (Parts 1 and 2) | Drug | 1 |
| tocilizumab [RoActemra/Actemra]2mg/kg-8mg/kg iv in Part 1 and selected dose in Part 2, on weeks 4, 8 and 12---Arm 1\n8mg/kg iv on weeks 4,8 and 12 (Parts 1 and 2)--- Arm 2 | Drug | 1, 2 |
Primary outcome
Percentage of Participants Achieving Low Disease Activity (LDA) at Week 16 Assessed Using Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR)
Time frame: Week 16
The Disease Activity Score based on 28 joint count (DAS28) and Erythrocyte Sedimentation Rate (ESR), is a measure of the participant's disease activity. It is based on the Tender Joint Count (TJC [28 joints]), Swollen Joint Count (SJC [28 joints]), participant's global assessment of disease activity (PtGA) Visual Analog Scale (VAS) in millimeters (mm), and ESR in millimeters per hour (mm/hour). DAS28-ESR scores range from 0 - 10. Definition of LDA was based on DAS28-ESR scores. To achieve LDA the DAS28-ESR had to be (less than or equal to) ≤ 3.2. DAS28-ESR equals (=) (0.56 times (*) (square root)√ TJC plus (+) (0.28 * √ SJC + (0.70 * ln(ESR))+(0.014 * (Global Health) GH) Where: TJC = based on 28 joints SJC = based on 28 joints ESR = erythrocyte sedimentation rate in mm/hour GH = participant's global assessment of disease activity ln = natural log
12 secondary outcomes
Percentage of Participants Achieving Remission at Week 16 Assessed Using DAS28-ESR
Time frame: Week 16
Percentage of Participants by European League Against Rheumatism (EULAR) Response Category at Week 16
Time frame: Week 16
Change From Baseline in DAS28-ESR
Time frame: Weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48
Clinical Disease Activity Index Scores
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48
Simplified Disease Activity Index (SDAI) Scores
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40, and 48
Change From Baseline to Week 48 in SJC and TJC
Time frame: Baseline and Week 48
Change From Baseline to Week 48 in Health Assessment Questionnaire (HAQ)
Time frame: Baseline and Week 48
Change From Baseline to Week 48 in C-Reactive Protein (CRP)
Time frame: Baseline and Week 48
Change From Baseline to Week 48 in ESR
Time frame: Baseline and Week 48
Change From Baseline to Week 48 in Physician's Global Assessment of Disease Activity
Time frame: Baseline and Week 48
Change From Baseline to Week 48 in Participant's Global Assessment of Disease Activity
Time frame: Baseline and Week 48
Change From Baseline to Week 48 in Participant's Assessment of Pain
Time frame: Baseline and Week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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
24 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing rituximab [MabThera/Rituxan] and tocilizumab [RoActemra/Actemra] in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 24 sites in 8 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 6 inclusion and 5 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: stopped early, as of the sponsor's last update on 24 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in Germany, France, Spain, Poland, Greece and 3 more countries. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 24 Dec 2014). 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 Low Disease Activity (LDA) at Week 16 Assessed Using Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) (time frame: Week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Dec 2014.