Rheumatoid ArthritisPhase 2NCT02093026
Extension Study to Assess the Efficacy and Safety of Repeat Treatment With Rituximab (MabThera) in Participants With Active Rheumatoid Arthritis (RA)
A Phase 2 study testing Rituximab, Methotrexate and Methylprednisolone in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 92 sites in 16 countries.
Trial summary
This study will assess the long-term safety and efficacy of repeat treatment courses of rituximab, in combination with methotrexate in a disease-modifying anti-rheumatic drug (DMARD) inadequate responder population of participants who were previously randomized into studies WA16291 (NCT02693210) or WA17043/U2644g… Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Rituximab, Methotrexate and Methylprednisolone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 465 participants
- Where
- 92 sitesin 16 countries
- Study dates
- Aug 2002to Dec 2012
- 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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- participants with active RA
- completed 24 weeks of treatment in WA16291 or WA17043
- eligible for re-treatment, based on clinical symptoms (Disease Activity Score in 28 joints >=2.6)
- females of childbearing potential using reliable contraception
Who cannot join
- participants who participated in rituximab studies WA16291 or WA17043 but withdrew into the safety follow-up phases of these trials
- previous rituximab non-responders
- current treatment with any other disease-modifying drug (apart from methotrexate), or any anti-tumor necrosis factor alfa, anti-interleukin-1, or other biologic therapies
- participants with known active infection of any kind
- evidence of any new or uncontrolled concomitant disease or development of any new contraindications which would preclude repeat treatment with rituximab
- history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
- female participants who are pregnant or breastfeeding
Trial locations and contacts
92 sites in 16 countries.
92 sites in 16 countries
United States42 sites
Study site
Aventura, Florida, 33180
Study site
Beachwood, Ohio, 44122
Study site
Birmingham, Alabama, 35294
Study site
Boca Raton, Florida, 33486
Study site
Boise, Idaho, 83702
Study site
Boston, Massachusetts, 02215
Study site
Chicago, Illinois, 60611
Study site
Chicago, Illinois, 60637
Study site
Colorado Springs, Colorado, 80920
Study site
Dallas, Texas, 75231
Study site
Dayton, Ohio, 45402
Study site
Duncansville, Pennsylvania, 16635
Study site
Fort Lauderdale, Florida, 33334
Study site
Glendale, Wisconsin, 53217
Study site
Great Neck, New York, 11021
Study site
Greenville, North Carolina, 27834
Study site
Houston, Texas, 77074
Study site
Indianapolis, Indiana, 46202-5149
Study site
Indianapolis, Indiana, 46260
Study site
La Jolla, California, 92037
Study site
Largo, Florida, 33773
Study site
Lebanon, New Hampshire, 03756
Study site
Little Rock, Arkansas, 72205
Study site
Long Beach, California, 92813
Study site
Mayfield, Ohio, 44143
Study site
Minneapolis, Minnesota, 55416
Study site
Peoria, Arizona, 85381
Study site
Plainview, New York, 11803
Study site
Portland, Oregon, 97239
Study site
Rancho Mirage, California, 92270
Study site
Rochester, New York, 14618
Study site
Salt Lake City, Utah, 84132
Study site
San Diego, California, 92108
Study site
Seattle, Washington, 98104
Study site
Smithtown, New York, 11787
Study site
South Miami, Florida, 33143
Study site
St Louis, Missouri, 63141
Study site
Tulsa, Oklahoma, 74104
Study site
Tulsa, Oklahoma, 74135
Study site
Voorhees Township, New Jersey, 08043
Study site
Wausau, Wisconsin, 54401
Study site
Winston-Salem, North Carolina, 27157
Spain7 sites
Study site
Madrid, Madrid, 28006
Study site
Madrid, Madrid, 28007
Study site
Madrid, Madrid, 28046
Study site
Mérida, Badajoz, 06800
Study site
San Cristóbal de La Laguna, Tenerife, 38320
Study site
Santiago de Compostela, La Coruña, 15706
Study site
Seville, Sevilla, 41014
Germany5 sites
Study site
Cologne, 50924
Study site
Leipzig, 04103
Study site
Ratingen, 40882
Study site
Regensburg, 93053
Study site
Würzburg, 97080
Poland5 sites
Study site
Bialystok, 15-351
Study site
Lublin, 20-022
Study site
Poznan, 61-545
Study site
Warsaw, 02-637
Study site
Wroclaw, 50-556
United Kingdom5 sites
Study site
Birmingham, B29 6JD
Study site
Cambridge, CB2 2QQ
Study site
Cannock, WS11 5XY
Study site
Leeds, LS7 4SA
Study site
Stoke-on-Trent, ST6 7AG
Canada4 sites
Study site
Calgary, Alberta, T2N 4Z6
Study site
London, Ontario, N6A 4V2
Study site
St. John's, Newfoundland and Labrador, A1A 5E8
Study site
Vancouver, British Columbia, V5Z 1L7
Italy4 sites
Study site
Genoa, Liguria, 16132
Study site
Milan, Lombardy, 20157
Study site
Modena, Emilia-Romagna, 41100
Study site
Udine, Friuli Venezia Giulia, 33100
Mexico4 sites
Study site
México, 44620
Study site
Mexico City, 06726
Study site
Mexico City, 10700
Study site
Monterrey, 64460
Australia3 sites
Study site
Maroochydore, Queensland, 4558
Study site
Melbourne, Victoria, 3168
Study site
Perth, Western Australia, 6979
Brazil3 sites
Study site
Campinas, São Paulo, 13083-888
Study site
Curtiba, Paraná, 80030-110
Study site
São Paulo, São Paulo, 04026-000
About this study
Official title: An Open-label Study of the Efficacy and Safety of Re-treatments With Rituximab (MabThera®/Rituxan®) in Patients With Active Rheumatoid Arthritis
This study will assess the long-term safety and efficacy of repeat treatment courses of rituximab, in combination with methotrexate in a disease-modifying anti-rheumatic drug (DMARD) inadequate responder population of participants who were previously randomized into studies WA16291 (NCT02693210) or WA17043/U2644g (NCT00074438). The study permits multiple re-treatments until the protocol-defined end-of-treatment date (31 December 2011). Participants will then enter a safety follow-up (SFU) period of at least 48 weeks. This will provide at least 7 years follow-up data on all participants initially randomized into WA16291 or WA17043/U2644g. Approximately 600 participants will potentially be eligible to enter this open label extension study from their respective feeder studies.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Rituximab, Methotrexate, Methylprednisolone, Folic Acid
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called MabThera, Rituxan
Participants will receive rituximab 1 gram IV on Days 1 and 15 of each course of retreatment.
MethotrexateDrug
Participants will receive methotrexate 10-25 mg/week orally or parenterally.
Participants will receive methylprednisolone 100 mg IV 30 minutes prior to each rituximab infusion.
Folic AcidDrug
Participants will receive folic acid >= 5 mg/week or equivalent.
| Study group | Role | What they receive |
|---|---|---|
| Rituximab | Experimental | Participants will receive rituximab 1 gram intravenously (IV) on Days 1 and 15 of each course of retreatment. In addition, participants will receive methotrexate 10-25 milligrams per week (mg/week) orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid greater than or equal to (>=) 5 mg/week or equivalent. Participants will receive retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first [Day 1] infusion of the last course of rituximab). Repeat treatment will be based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints >=2.6). Retreatment with rituximab will be continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever is sooner. Receives: Drug: Rituximab; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Folic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With an American College of Rheumatology 20 (ACR20) Response After First Course
A participant had an ACR20 response if there was at least a 20 percent (%) improvement, ie, reduction from Baseline, in tender joint count (TJC) and swollen joint count (SJC) (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [visual analog scale (VAS): 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either C-reactive protein [CRP] or erythrocyte sedimentation rate [ESR]). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Measured: 24 weeks after first course of rituximab (up to approximately 26 weeks)
Percentage of Participants With ACR20 Response After Second Course
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Measured: 24 weeks after second course of rituximab (median duration of 90.9 weeks)
Percentage of Participants With ACR20 Response After Third Course
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Measured: 24 weeks after third course of rituximab (median duration of 162.9 weeks)
Percentage of Participants With ACR20 Response After Fourth Course
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Measured: 24 weeks after fourth course of rituximab (median duration of 232 weeks)
Percentage of Participants With ACR20 Response After Fifth Course
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Measured: 24 weeks after fifth course of rituximab (median duration of 297.3 weeks)
Percentage of Participants With ACR20 Response After Sixth Course
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Measured: 24 weeks after sixth course of rituximab (median duration of 354.4 weeks)
Percentage of Participants With ACR20 Response After Seventh Course
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Measured: 24 weeks after seventh course of rituximab (median duration of 406.7 weeks)
Secondary outcomes (8)
Percentage of Participants With ACR50 and ACR70 Response
A participant had an ACR50 and ACR70 response if there was at least a 50% or 70% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of disease activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (CRP or ESR). The ACR50 and ACR70 responses were compared to Baseline in the precursor studies WA16291 or WA17043.
Measured: 24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)
American College of Rheumatology Index of Improvement (ACRn) Response
The ACRn is calculated for each participant by taking the lowest percentage improvement in (1) SJC or (2) TJC or (3) the median of the remaining 5 components of the ACR response (patient's assessment of disease activity; patient's global assessment of pain; physician's assessment of disease activity; participant's assessment of physical function; an acute phase reactant value [either CRP or ESR]). The index of improvement in RA, where 0 indicates no improvement and 100 indicates a 100% improvement across all signs and symptoms of RA. ACRn scores were calculated considering the original baseline in the precursor studies WA16291 or WA17043.
Measured: 24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)
Percentage of Participants With Low Disease Activity and Clinical Remission Based on DAS28-ESR
DAS28-ESR was calculated from SJC and TJC using 28 joints count, ESR (millimeters per hour [mm/hour]), and Patient's Global Assessment of Disease Activity (VAS: 0=no disease activity to 100=maximum disease activity). DAS28-ESR = 0.56*square root (sqrt)(TJC28) + 0.28*sqrt(SJC28) + 0.70*natural logarithm (ln) (ESR) + 0.014*Patient's Global Assessment of Disease Activity. Total score range: 0-10, higher score=more disease activity. DAS28-ESR <= 3.2 implied low disease activity (LDA) and DAS28-ESR <2.6 = clinical remission.
Measured: 24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)
Percentage of Participants With European League Against Rheumatism (EULAR) Response of 'Good' or 'Moderate'
DAS28-ESR was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and Physician's Global Assessment of Disease Activity (VAS: 0=no disease activity to 100=maximum disease activity). DAS28-ESR = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.70*ln(ESR) + 0.014*Patient's Global Assessment of Disease Activity. The 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 had a change from baseline greater than (>) 1.2 with a DAS28 score less than or equal to (≤) 3.2; moderate responders had a change from baseline >1.2 with a DAS28 score >3.2 to less than or equal to (≤) 5.1 or a change from baseline >0.6 to ≤1.2 with a DAS28 score ≤5.1.
Measured: 24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)
Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at 24 Weeks Following Each Course
The HAQ-DI is a questionnaire specific for rheumatoid arthritis and consists of 20 questions referring to 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Participants completed the questionnaire by answering the 20 questions on a scale of 0 (without difficulty) to 3 (unable to do). The total score ranges from 0 (no disability) to 3 (completely disabled). A negative change score indicates improvement.
Measured: 24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)
Change From Baseline in Total Rheumatoid Factors (RF) at 24 Weeks Following Each Course
Measured: 24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)
Percentage of Participants Who Discontinued Treatment Due to Insufficient Response
Measured: First, second, third, fourth, fifth, sixth, and seventh course of rituximab (up to a median of approximately 2, 62, 124, 186, 248, 310, and 372 weeks, respectively)
Time Since Last Treatment Course
Time since last treatment course = The last day of the last dose of rituximab to date of last contact. Date of last contact is the last available date of efficacy, complete medication start date, laboratory, adverse event assessments, early withdrawal visit, date of last contact, or date of death.
Measured: Baseline up to 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2014 (estimated)
- Study startAug 2002
- Primary completionDec 2012
- Study completionDec 2012
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 465 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study chair, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02093026
- Sponsor's protocol ID
- WA16855
- Other IDs
- U2653g
- Status last verified
- Jan 2017
- First submitted
- 19 Mar 2014
- Last updated
- 13 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Study of the Efficacy and Safety of Re-treatments With Rituximab (MabThera®/Rituxan®) in Patients With Active Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT02093026
- Acronym / sponsor ID
- WA16855
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 465 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Collaborators
- Genentech, Inc.
- Study start
- Aug 2002
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 20 Mar 2014 (estimated)
- Results
- Posted 13 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess the long-term safety and efficacy of repeat treatment courses of rituximab, in combination with methotrexate in a disease-modifying anti-rheumatic drug (DMARD) inadequate responder population of participants who were previously randomized into studies WA16291 (NCT02693210) or WA17043/U2644g (NCT00074438). The study permits multiple re-treatments until the protocol-defined end-of-treatment date (31 December 2011). Participants will then enter a safety follow-up (SFU) period of at least 48 weeks. This will provide at least 7 years follow-up data on all participants initially randomized into WA16291 or WA17043/U2644g. Approximately 600 participants will potentially be eligible to enter this open label extension study from their respective feeder studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rituximab | Experimental | Drug: Rituximab, Drug: Methotrexate, Drug: Methylprednisolone, Drug: Folic AcidParticipants will receive rituximab 1 gram intravenously (IV) on Days 1 and 15 of each course of retreatment. In addition, participants will receive methotrexate 10-25 milligrams per week (mg/week) orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid greater than or equal to (>=) 5 mg/week or equivalent. Participants will receive retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first [Day 1] infusion of the last course of rituximab). Repeat treatment will be based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints >=2.6). Retreatment with rituximab will be continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever is sooner. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- participants with active RA
- completed 24 weeks of treatment in WA16291 or WA17043
- eligible for re-treatment, based on clinical symptoms (Disease Activity Score in 28 joints >=2.6)
- females of childbearing potential using reliable contraception
Key exclusion criteria (7 listed)
- participants who participated in rituximab studies WA16291 or WA17043 but withdrew into the safety follow-up phases of these trials
- previous rituximab non-responders
- current treatment with any other disease-modifying drug (apart from methotrexate), or any anti-tumor necrosis factor alfa, anti-interleukin-1, or other biologic therapies
- participants with known active infection of any kind
- evidence of any new or uncontrolled concomitant disease or development of any new contraindications which would preclude repeat treatment with rituximab
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 |
|---|---|---|
| RituximabAlso: MabThera, RituxanParticipants will receive rituximab 1 gram IV on Days 1 and 15 of each course of retreatment. | Drug | Rituximab |
| MethotrexateParticipants will receive methotrexate 10-25 mg/week orally or parenterally. | Drug | Rituximab |
| MethylprednisoloneParticipants will receive methylprednisolone 100 mg IV 30 minutes prior to each rituximab infusion. | Drug | Rituximab |
| Folic AcidParticipants will receive folic acid >= 5 mg/week or equivalent. | Drug | Rituximab |
Primary outcome
Percentage of Participants With an American College of Rheumatology 20 (ACR20) Response After First Course
Time frame: 24 weeks after first course of rituximab (up to approximately 26 weeks)
A participant had an ACR20 response if there was at least a 20 percent (%) improvement, ie, reduction from Baseline, in tender joint count (TJC) and swollen joint count (SJC) (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [visual analog scale (VAS): 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either C-reactive protein [CRP] or erythrocyte sedimentation rate [ESR]). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Percentage of Participants With ACR20 Response After Second Course
Time frame: 24 weeks after second course of rituximab (median duration of 90.9 weeks)
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Percentage of Participants With ACR20 Response After Third Course
Time frame: 24 weeks after third course of rituximab (median duration of 162.9 weeks)
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Percentage of Participants With ACR20 Response After Fourth Course
Time frame: 24 weeks after fourth course of rituximab (median duration of 232 weeks)
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Percentage of Participants With ACR20 Response After Fifth Course
Time frame: 24 weeks after fifth course of rituximab (median duration of 297.3 weeks)
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Percentage of Participants With ACR20 Response After Sixth Course
Time frame: 24 weeks after sixth course of rituximab (median duration of 354.4 weeks)
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
Percentage of Participants With ACR20 Response After Seventh Course
Time frame: 24 weeks after seventh course of rituximab (median duration of 406.7 weeks)
A participant had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0=no disease activity to 100=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0=no pain to 100=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR). The ACR20 response was compared to Baseline in the precursor studies WA16291 or WA17043.
8 secondary outcomes
Percentage of Participants With ACR50 and ACR70 Response
Time frame: 24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)
American College of Rheumatology Index of Improvement (ACRn) Response
Time frame: 24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)
Percentage of Participants With Low Disease Activity and Clinical Remission Based on DAS28-ESR
Time frame: 24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)
Percentage of Participants With European League Against Rheumatism (EULAR) Response of 'Good' or 'Moderate'
Time frame: 24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)
Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at 24 Weeks Following Each Course
Time frame: 24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)
Change From Baseline in Total Rheumatoid Factors (RF) at 24 Weeks Following Each Course
Time frame: 24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)
Percentage of Participants Who Discontinued Treatment Due to Insufficient Response
Time frame: First, second, third, fourth, fifth, sixth, and seventh course of rituximab (up to a median of approximately 2, 62, 124, 186, 248, 310, and 372 weeks, respectively)
Time Since Last Treatment Course
Time frame: Baseline up to 10 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2017.
- 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 chair
Hoffmann-La Roche
92 sites in 16 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab, Methotrexate and Methylprednisolone in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 92 sites in 16 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 4 inclusion and 7 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 13 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 92 sites in United States, Spain, Germany, Poland, United Kingdom and 11 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 13 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 an American College of Rheumatology 20 (ACR20) Response After First Course (time frame: 24 weeks after first course of rituximab (up to approximately 26 weeks)). The study lists 7 primary outcomes in all. 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 13 Mar 2017.