Rheumatoid ArthritisPhase 3NCT00503425
A Study of MabThera (Rituximab) in Participants With Rheumatoid Arthritis Who Have Had an Inadequate Response to Disease-Modifying Antirheumatic Drugs (DMARD) and/or Anti-Tumor Necrosis Factor (Anti-TNF) Therapy.
A Phase 3 study testing Rituximab [MabThera/Rituxan] in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 16 sites in Israel.
Trial summary
This single arm study will evaluate the safety and efficacy of MabThera in participants with active rheumatoid arthritis who have had an inadequate response to prior treatment with DMARDs and/or anti-TNF alpha agent. Participants will be treated with MabThera 1000 milligrams (mg) intravenously (IV) on days 1 and 15. 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?
- Rituximab [MabThera/Rituxan]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 215 participants
- Where
- 16 sitesIsrael
- Study dates
- 30 Jun 2005to 26 May 2013
- 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
- During study entry
- Able and willing to give written informed consent and comply with the requirements of the study protocol;
- Participants with Rheumatoid Arthritis (RA) for at least 6 months, diagnosed according to the revised 1987 American College of Rheumatology (ACR) criteria for the classification of RA;
- Receiving treatment on an outpatient basis;
- Experienced an inadequate response to previous or current treatment with DMARDs because of toxicity or inadequate efficacy;
- Disease activity score (DAS28) greater than or equal to (>=) 3.2 at screening and baseline visit.
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- Age >= 18 years;
- Participants of reproductive potential (males and females) using a reliable means of contraception (for example [e.g.] contraceptive pill, intrauterine device, physical barrier);
- Female participants with childbearing potential - a negative urine pregnancy test within two weeks prior to first rituximab treatment.
- During Re-Treatment
- Achieved moderate or good response according to the EULAR response criteria during any visit including visits in the post-treatment period;
- DAS28 >=3.2;
- The participants has not been withdrawn into the safety follow-up at any time pre or post Week 24;
- 36 weeks or more have passed since the participant's first rituximab infusion;
- No evidence of any new medical condition or laboratory test results;
- In participants who were known to be positive to hepatitis B core antibody (HBcAb) - documented negative hepatitis B viral DNA (HBV-DNA) test and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than or equal to (<=) 2.5x upper limit of normal (ULN) within the last 12 weeks;
- Female participants with childbearing potential - a negative urine pregnancy test immediately prior to treatment initiation.
Who cannot join
- Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis or Felty's syndrome). Sjogren's syndrome with RA was permitted;
- Functional class IV as defined by the ACR Classification of Functional Status in RA;
- History of, or current, inflammatory joint disease other than RA (e.g., gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease) or other systemic rheumatic disorder disorder (e.g., inflammatory bowel disease, scleroderma, inflammatory myopathy);
- Excluded Previous/Concomitant Medications
- Previous or concurrent treatment with any anti TNF-alpha therapy;
- Treatment with any investigational agent within 4 weeks of screening;
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- Previous treatment with any cell depleting therapies excluding rituximab, including investigational agents;
- Immunization with a live vaccine within 4 weeks prior to the baseline visit.
- Exclusions for General Safety
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies;
- Significant cardiac or pulmonary disease (including obstructive pulmonary disease).
- Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders.
- Known active bacterial, viral, fungal, mycobacterial or other infection (including tuberculosis, or atypical mycobacterial disease, but excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening;
- History of recurrent significant infection or history of recurrent bacterial infections;
- Primary or secondary immunodeficiency (history of, or currently active);
- Active cancer, including solid tumors and hematologic malignancies (except basal cell or squamous cell carcinoma of the skin that have been excised and cured);
- Pregnant women or nursing (breast feeding) mothers;
- Participants with lack of peripheral venous access;
- Laboratory Exclusion Criteria (at Screening)
- Positive tests for hepatitis B surface antigen (HBsAg) and/or positive tests for HBcAb associated with detectable HBV-DNA or hepatitis C antibody (HCAb) and hepatitis C viral RNA (HCV-RNA).
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
Israel16 sites
Barzilai; Rheumatology
Ashkelon, 78306
Assaf Harofe; Dept of Medicine B
Beer Yaakov, 6093000
Soroka Medical Center; Reumatology
Beersheba, 8410101
Hillel Yaffe MC; Internal C - Rheumatology
Hadera, 38100
Rambam Medical Center; Rheumatology
Haifa, 3109601
Bnei Zion Medical Center; Rheumatology
Haifa, 3339419
Carmel Hospital; Rheumatology Dept
Haifa, 34362
Wolfson Hospital; Rheumatology
Holon, 58100
Hadassah Mount Scopus Hospital; Rheumatology
Jerusalem, 91240
Meir Medical Center; Internal Dept A
Kfar Saba, 44281
Nahariya Hospital; Rheumatology Dept
Nahariya, 22100
Shaare Zedek Medical Center; Rheumatology Dept
Nahariya, 22100
EMMS Nazareth; Internal Department A
Nazareth, 16100
Beilinson Medical Center; Rheumatology
Petah Tikva, 4941492
Kaplan Medical Center; Reumatology
Rehovot, 76100
Sourasky / Ichilov Hospital; Rheumatology
Tel Aviv, 6423906
About this study
Official title: An Open Label Study to Assess the Safety and Effect on Disease Activity of MabThera in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Prior Treatment With DMARDs and/or One Anti-TNF Alpha Agent
This single arm study will evaluate the safety and efficacy of MabThera in participants with active rheumatoid arthritis who have had an inadequate response to prior treatment with DMARDs and/or anti-TNF alpha agent. Participants will be treated with MabThera 1000 milligrams (mg) intravenously (IV) on days 1 and 15. Participants were followed every 8 weeks to complete 24 weeks of follow-up. After completion of the Week 24 visit, the participants were followed every 3 months for up to 18 months for an overall study duration of 24 months (104 weeks). After week 36, eligible participants who achieve moderate or good response according to the European League Against Rheumatism (EULAR) response criteria will receive re-treatment with MabThera. Participants will receive concomitant treatment with DMARDs, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics throughout the study period. The anticipated time on study treatment is 2 years, and the target sample size is 200 participants.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Rituximab [MabThera/Rituxan]
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rituximab [MabThera/Rituxan]Drug
1000 mg IV on days 1 and 15
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: Rituximab [MabThera/Rituxan] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Number of participants with non-serious AEs was exclusive of SAEs.
Measured: Baseline up to study withdrawal or follow-up (Approximately 104 weeks)
Secondary outcomes (4)
Mean Change From Baseline in Disease Activity Score Based on 28 Joints (DAS 28) at Week 24
DAS28 score is a measure of participant's disease activity calculated using tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], participant's global assessment of disease activity (PGH) [visual analog scale (VAS): 0=no disease activity to 100=maximum disease activity] and erythrocyte sedimentation rate (ESR). DAS28 was calculated according to following formula: 0.56 multiplied by (*) square root (√) of TJC] plus (+) [0.28*√SJC]+[0.70*the natural logarithm (ln) ESR]+[0.014*PGH]. Total possible score of 0 to approximately 10, where higher scores represented higher disease activity. Scores below 2.6 indicated clinical remission, score of less than or equals to (</=) 3.2 indicated low disease activity, score of </=5.1 indicated moderate disease activity, scores above 5.1 indicated high or severe disease. Rituximab was administered as needed during episodes of inflammation for up to 5 courses. Change from baseline in DAS28 to Week 24 was reported for all 5 courses.
Measured: Baseline, Week 24
Percentage of Participants Whose DAS28 Improved by Greater Than (>) 1.2 at Week 24
DAS28 score is a measure of participant's disease activity calculated using TJC28, SJC28, PGH [VAS: 0=no disease activity to 100=maximum disease activity] and ESR. DAS28 was calculated according to following formula: [0.56*√TJC] + [0.28*√SJC] + [0.70*ln ESR] + [0.014*PGH]. Total possible score of 0 to approximately 10, where higher scores represented higher disease activity. Scores below 2.6 indicated clinical remission, score of </= 3.2 indicated low disease activity, score of </= 5.1 indicated moderate disease activity, and scores above 5.1 indicated high or severe disease. Rituximab was administered as needed during episodes of inflammation for up to 5 courses. Change from baseline in DAS28 to Week 24 was reported for all 5 courses. Participants whose DAS28 score improved by 1.2 score were reported.
Measured: Week 24
Percentage of Participants With EULAR DAS 28 Response at Week 24
Clinical response was assessed according to EULAR categorical DAS28 response criteria, which defined clinically meaningful improvement at Week 24. EULAR response was based on change from baseline (COB) in DAS28 score and also on actual DAS28 score, at Week 24. DAS28 score= participant's disease activity calculated using TJC28, SJC28, PGH [VAS: 0=no disease activity to 100=maximum disease activity] and ESR. DAS28 was calculated by following formula: 0.56*√TJC+(0.28*√SJC)+(0.70*ln ESR)+(0.014*PGH). Total possible score=0-10, higher scores represented higher disease activity. Scores below 2.6: clinical remission, </=3.2: low disease activity, </=5.1: moderate disease activity, above 5.1: severe disease. EULAR Good response: DAS28</=3.2; COB<-1.2. Moderate response: DAS28</=3.2 or >3.2 to </=5.1 or >5.1; COB <-1.2 or <-0.6 to greater than or equal to (>/=)-1.2. No response: DAS28 </=3.2 or > 3.2 to </=5.1 or >5.1; COB <-0.6 to >/=-1.2 or >/=-0.6. EULAR response was reported for 5 courses.
Measured: Week 24
Change From Baseline in Bone Density Score at Weeks 48 and 104
Bone density or bone mineral density (BMD) is the amount of bone mineral in bone tissue. BMD test results are compared to the ideal or peak BMD of a healthy 30-year-old adult, and results are provided as T-score. A score of 0 means BMD is equal to the norm for a healthy young adult. Differences between observed BMD and that of the healthy young adult norm are measured in units called standard deviations (SDs). The more standard deviations below 0, indicated as negative numbers, lower the BMD higher the risk of fracture. SD + 1 to -1 indicates normal BMD; SD between -1 to -2.5 indicates low bone mass, SD -2.5 or lower indicates osteoporosis. Change in bone density was measured in participants who were not treated with biphosphonates by Dual Energy X-Ray Absorptiometry. Change in bone density was assessed at baseline and at Weeks 48 and 104. Change from baseline in bone density score was reported for all 5 courses.
Measured: Baseline, Weeks 48 and 104 (End of treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2007 (estimated)
- Study start30 Jun 2005
- Primary completion26 May 2013
- Study completion26 May 2013
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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 215 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
- NCT00503425
- Sponsor's protocol ID
- ML18606
- Status last verified
- Jun 2017
- First submitted
- 17 Jul 2007
- Last updated
- 15 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Study to Assess the Safety and Effect on Disease Activity of MabThera in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Prior Treatment With DMARDs and/or One Anti-TNF Alpha Agent
- ClinicalTrials.gov ID
- NCT00503425
- Acronym / sponsor ID
- ML18606
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 215 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 30 Jun 2005 (actual)
- Primary completion
- 26 May 2013 (actual)
- Study completion
- 26 May 2013 (actual)
- First posted
- 18 Jul 2007 (estimated)
- Results
- Posted 23 Jun 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This single arm study will evaluate the safety and efficacy of MabThera in participants with active rheumatoid arthritis who have had an inadequate response to prior treatment with DMARDs and/or anti-TNF alpha agent. Participants will be treated with MabThera 1000 milligrams (mg) intravenously (IV) on days 1 and 15. Participants were followed every 8 weeks to complete 24 weeks of follow-up. After completion of the Week 24 visit, the participants were followed every 3 months for up to 18 months for an overall study duration of 24 months (104 weeks). After week 36, eligible participants who achieve moderate or good response according to the European League Against Rheumatism (EULAR) response criteria will receive re-treatment with MabThera. Participants will receive concomitant treatment with DMARDs, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics throughout the study period. The anticipated time on study treatment is 2 years, and the target sample size is 200 participants.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Rituximab [MabThera/Rituxan] |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- During study entry
- Able and willing to give written informed consent and comply with the requirements of the study protocol;
- Participants with Rheumatoid Arthritis (RA) for at least 6 months, diagnosed according to the revised 1987 American College of Rheumatology (ACR) criteria for the classification of RA;
- Receiving treatment on an outpatient basis;
- Experienced an inadequate response to previous or current treatment with DMARDs because of toxicity or inadequate efficacy;
Key exclusion criteria (20 listed)
- Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis or Felty's syndrome). Sjogren's syndrome with RA was permitted;
- Functional class IV as defined by the ACR Classification of Functional Status in RA;
- History of, or current, inflammatory joint disease other than RA (e.g., gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease) or other systemic rheumatic disorder disorder (e.g., inflammatory bowel disease, scleroderma, inflammatory myopathy);
- Excluded Previous/Concomitant Medications
- Previous or concurrent treatment with any anti TNF-alpha therapy;
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 |
|---|---|---|
| Rituximab [MabThera/Rituxan]1000 mg IV on days 1 and 15 | Drug | 1 |
Primary outcome
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Baseline up to study withdrawal or follow-up (Approximately 104 weeks)
An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Number of participants with non-serious AEs was exclusive of SAEs.
4 secondary outcomes
Mean Change From Baseline in Disease Activity Score Based on 28 Joints (DAS 28) at Week 24
Time frame: Baseline, Week 24
Percentage of Participants Whose DAS28 Improved by Greater Than (>) 1.2 at Week 24
Time frame: Week 24
Percentage of Participants With EULAR DAS 28 Response at Week 24
Time frame: Week 24
Change From Baseline in Bone Density Score at Weeks 48 and 104
Time frame: Baseline, Weeks 48 and 104 (End of treatment)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 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 director
Hoffmann-La Roche
16 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 Rituximab [MabThera/Rituxan] in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 16 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 17 inclusion and 20 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 15 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 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 23 Jun 2016). 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?
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: Baseline up to study withdrawal or follow-up (Approximately 104 weeks)). 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 15 Aug 2017.