Trial Outcomes & Findings for A Pharmacokinetic and Pharmacodynamic Study of MabThera (Rituximab) Plus Methotrexate in Patients With Rheumatoid Arthritis (RA) (NCT NCT00422942)
NCT ID: NCT00422942
Last Updated: 2014-07-16
Results Overview
The change from baseline in absolute B cell (CD19+) counts at each visit calculated as (B cell count at visit minus B cell count at baseline) for synovial tissues.
TERMINATED
PHASE2
3 participants
Weeks 12, 24, and 36
2014-07-16
Participant Flow
Participant milestones
| Measure |
Rituximab + Methotrexate (MTX)
Participants received rituximab 1000 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 and also on Days 169 and 183 (for those meeting retreatment criteria) or as needed (PRN) if retreatment criteria were not met; premedication with methylprednisolone (MP) 100 mg IV was administered at least 30 minutes prior to each rituximab infusion. Participants also received MTX 10-25 mg per week (mg/week; oral or parenteral) for up to 48 weeks and folate (greater than or equal to \[≥\]5 mg/week) given as either a single weekly dose or as divided dose for up to 48 weeks.
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|---|---|
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Overall Study
STARTED
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3
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Overall Study
COMPLETED
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0
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Overall Study
NOT COMPLETED
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3
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Reasons for withdrawal
| Measure |
Rituximab + Methotrexate (MTX)
Participants received rituximab 1000 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 and also on Days 169 and 183 (for those meeting retreatment criteria) or as needed (PRN) if retreatment criteria were not met; premedication with methylprednisolone (MP) 100 mg IV was administered at least 30 minutes prior to each rituximab infusion. Participants also received MTX 10-25 mg per week (mg/week; oral or parenteral) for up to 48 weeks and folate (greater than or equal to \[≥\]5 mg/week) given as either a single weekly dose or as divided dose for up to 48 weeks.
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|---|---|
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Overall Study
Study terminated by Sponsor
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3
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Baseline Characteristics
A Pharmacokinetic and Pharmacodynamic Study of MabThera (Rituximab) Plus Methotrexate in Patients With Rheumatoid Arthritis (RA)
Baseline characteristics by cohort
Baseline data not reported
PRIMARY outcome
Timeframe: Weeks 12, 24, and 36Population: No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered.
The change from baseline in absolute B cell (CD19+) counts at each visit calculated as (B cell count at visit minus B cell count at baseline) for synovial tissues.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Weeks 4, 12, 24, 36, and 48Population: No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered.
The change from baseline in absolute B cell (CD19+) count at each visit calculated as (B cell count at visit minus B cell count at baseline) for peripheral blood.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Weeks 12, 24, and 36Population: No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered.
The change in absolute counts of cells expressing the key B cell markers (CD20+ and CD22+) in absolute B cell (CD19+) counts in synovial tissues at Weeks 12, 24, and 36, relative to baseline.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Weeks 4,12, 24, 36, and 48Population: No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered.
The change in absolute counts of cells expressing the key B cell markers (CD20+ and CD22+) in absolute B cell (CD19+) counts in peripheral blood at Weeks 4,12, 24, 36, and 48, relative to baseline.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Days 15 and 183 and Weeks 4, 12, 24, 36, and 48Population: No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered.
The change in levels of key cytokines (IL-1β, TNF-α, IL-4, IL-6, IL-10, and IL-13) in blood (serum) on Days 15 and 183 and at Weeks 4, 12, 24, 36, and 48, relative to baseline.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Weeks 12, 24, and 36Population: No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered.
The change in levels of key cytokines in (IL-1β, TNF-α, IL-6, and IL-10) in synovial tissues at Weeks 12, 24, and 36, relative to baseline.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Days 15 and 183Population: No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered.
The change in ribonucleic acid (RNA) expression of markers of apoptosis (C-myc and BAX) in peripheral blood at Days 15 and 183, relative to baseline.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Week 48Population: No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered.
ACR20/50/70 response is greater than or equal to (≥) 20%, 50%, or 70% improvement, respectively, in tender joint count (TJC) and swollen joint count (SJC); and improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Weeks 12, 24, 36, and 48Population: No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered.
The change in DAS28-ESR at Weeks 12, 24, 36, and 48, relative to baseline. DAS28-ESR was calculated from SJC and TJC using 28-joint count, ESR (millimeters per hour \[mm/hour\]) and patient global assessment of disease activity (participant-rated arthritis activity assessment). Total score range: 0-9.4, higher score equals (=) more disease activity. DAS28-ESR less than or equal to (≤) 3.2 implied low disease activity and greater than (\>)3.2 to 5.1 implied moderate to high disease activity, and DAS28-ESR \<2.6 = remission.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Weeks 24, 36, and 48Population: No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered.
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: change from baseline \>1.2 with DAS28 ≤ 3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to ≤ 5.1 or change from baseline \>0.6 to ≤ 1.2 with DAS28 ≤ 5.1; non-responders: change from baseline ≤ 0.6 or change from baseline \>0.6 and ≤ 1.2 with DAS28 \>5.1.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Week 48Population: No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered.
The changes from baseline in the ACR core set parameters at Week 48. Change from baseline to Week 48 over time in ACR core set: SJC, TJC, physician's global assessment of disease activity, patient's global assessment of disease activity, patient's assessment of pain, HAQ, ESR, and CRP. ACR20/50/70 response: ≥20%/50%/70% improvement in SJC; ≥20%/50%/70% improvement in TJC; and ≥20%/50%/70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; physician's global assessment of disease activity, participant's assessment of disease activity, participant assessment of functional disability via a HAQ, and CRP at each visit.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Weeks 24 and 48Population: No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered.
mTSS = sum of erosion and Joint Space Narrowing (JSN) scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change: scores at observation minus score at baseline. An increase in mTSS from baseline. An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Weeks 24 and 48Population: No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered.
Changes from baseline in modified Sharp radiographic erosion score from baseline to Weeks 24 and 48. The change in score at week X (where X=Week 24 or Week 48, as appropriate) calculated as: Change = week X score minus screening score.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Weeks 24 and 48Population: No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered.
Changes from baseline in modified Sharp radiographic JSN score from baseline to Weeks 24 and 48. The change in score at week X (where X=Week 24 or Week 48, as appropriate) calculated as: Change = week X score minus screening score.
Outcome measures
Outcome data not reported
Adverse Events
Rituximab + MTX
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER