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NCT00502840

A Study of Re-Treatment With MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to a Single Anti-TNF Inhibitor.

Completed Phase 3 Results posted Last updated 18 August 2017
What this trial tests

Phase 3 trial testing rituximab [MabThera/Rituxan] in Rheumatoid Arthritis in 193 participants. Completed in 20 September 2011.

Timeline
23 July 2007
Primary endpoint
20 September 2011
20 September 2011

Quick facts

Lead sponsorHoffmann-La Roche
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment193
Start date23 July 2007
Primary completion20 September 2011
Estimated completion20 September 2011
Sites51 locations across Germany

Drugs / interventions tested

Conditions studied

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

Adults 18 to 75, any sex, with Rheumatoid Arthritis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in DAS28 Score at Week 24 Primary · Week 24

DAS28 calculated from the swollen joint count (SJC) and tender joint count (PJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and Patient Global Asessment of disease activity (participant- rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). A clinically meaningful improvement in DAS28 was defined as an improvement of 1.2 units.

GroupValue95% CI
Rituximab Plus MTX-2.12± 1.41
DAS28 Score by Treatment Course and Follow-up (FU) Visit Secondary · Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12

DAS28 was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). The DAS28 consists of SJC and TJC measurements, the ESR (measured in mm/hr), and Patient Global Asessment of disease activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 less than or equal to (≤)3.2 equals (=) low disease activity, DAS28 \>3.2 to 5.1 = moderate to high disease activity.

Screening (n=173)
GroupValue95% CI
Rituximab Plus MTX5.15± 1.09
Course 1: FU Week 8 (n=171)
GroupValue95% CI
Rituximab Plus MTX4.09± 1.22
Course 1: FU Week 16 (n=167)
GroupValue95% CI
Rituximab Plus MTX3.72± 1.29
Course 1: FU Week 24 (n=163)
GroupValue95% CI
Rituximab Plus MTX3.78± 1.25
Course 1: FU Month 9 (n=76)
GroupValue95% CI
Rituximab Plus MTX3.94± 1.56
Course 1: FU Month 12 (n=38)
GroupValue95% CI
Rituximab Plus MTX3.79± 1.38
Course 2: FU Week 8 (n=104)
GroupValue95% CI
Rituximab Plus MTX3.69± 1.25
Course 2: FU Week 16 (n=106)
GroupValue95% CI
Rituximab Plus MTX3.34± 1.04
Percentage of Participants With European League Against Rheumatism (EULAR) Response of 'Good' or 'Moderate' by Treatment Course Secondary · Week 24

DAS28 was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). 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 \>1.2 with a DAS28 score ≤3.2; moderate responders had a change from baseline \>1.2 with a DAS28 score \>3.2 to ≤5.1 or a change from baseline \>0.6 to ≤1.2 with a DAS28 score ≤

Course 1 (n=173)
GroupValue95% CI
Rituximab Plus MTX78.0
Course 2 (n=107)
GroupValue95% CI
Rituximab Plus MTX86.9
Course 3 (n=38)
GroupValue95% CI
Rituximab Plus MTX86.8
Percentage of Participants Achieving a Response By EULAR Category and Treatment Course Secondary · Week 24

Response was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). 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 \>1.2 with a DAS28 score ≤3.2; moderate responders had a change from baseline \>1.2 with a DAS28 score \>3.2 to ≤5.1 or a change from baseline \>0.6 to ≤1.2 with a DAS28 scor

Course 1: Good response (n=173)
GroupValue95% CI
Rituximab Pluse MTX32.4
Course 1: Moderate response (n=173)
GroupValue95% CI
Rituximab Pluse MTX45.7
Course 2: Good response (n=107)
GroupValue95% CI
Rituximab Pluse MTX43.0
Course 2: Moderate response (n=107)
GroupValue95% CI
Rituximab Pluse MTX43.9
Course 3: Good response (n=38)
GroupValue95% CI
Rituximab Pluse MTX44.7
Course 3: Moderate response (n=38)
GroupValue95% CI
Rituximab Pluse MTX42.1
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score by Treatment Course Secondary · Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12

HAQ-DI was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). The HAQ-DI score consists of questions referring to 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. For each of the categories, participants reported the amount of difficulty they had in performing 2 or 3 specific sub-category items. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. The st

Screening (n=173)
GroupValue95% CI
Rituximab Plus MTX1.43± 0.64
Course 1: FU Week 8 (n=171)
GroupValue95% CI
Rituximab Plus MTX1.36± 0.68
Course 1: FU Week 16 (n=164)
GroupValue95% CI
Rituximab Plus MTX1.31± 0.67
Course 1: FU Week 24 (n=164)
GroupValue95% CI
Rituximab Plus MTX1.28± 0.68
Course 1: FU Month 9 (n=76)
GroupValue95% CI
Rituximab Plus MTX1.33± 0.72
Course 1: FU Month 12 (n=39)
GroupValue95% CI
Rituximab Plus MTX1.29± 0.84
Course 2: FU Week 8 (n=100)
GroupValue95% CI
Rituximab Plus MTX1.31± 0.62
Course 2: FU Week 16 (n=104)
GroupValue95% CI
Rituximab Plus MTX1.26± 0.61
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score by Treatment Course Secondary · Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12

FACIT-F was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). The FACIT fatigue scale is based on a 13-item questionnaire to assess the therapy-induced fatigue. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the participant's response to the questions (with the exception of 2 negatively stated), greater was the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was

Screening (n=169)
GroupValue95% CI
Rituximab Plus MTX20.16± 11.37
Course 1: FU Week 8 (n=165)
GroupValue95% CI
Rituximab Plus MTX18.48± 11.39
Course 1: FU Week 16 (n=157)
GroupValue95% CI
Rituximab Plus MTX18.81± 12.14
Course 1: FU Week 24 (n=161)
GroupValue95% CI
Rituximab Plus MTX17.75± 11.76
Course 1: FU Month 9 (n=72)
GroupValue95% CI
Rituximab Plus MTX18.17± 12.53
Course 1: FU Month 12 (n=35)
GroupValue95% CI
Rituximab Plus MTX20.77± 13.48
Course 2: FU Week 8 (n=99)
GroupValue95% CI
Rituximab Plus MTX16.43± 11.18
Course 2: FU Week 16 (n=101)
GroupValue95% CI
Rituximab Plus MTX16.19± 11.22
Short-Form 36 (SF-36) Physical Composite Scores (PCS) by Treatment Course Secondary · Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12

SF-36 was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and genera

Screening (n=171)
GroupValue95% CI
Rituximab Plus MTX34.57± 7.83
Course 1: FU Week 8 (n=165)
GroupValue95% CI
Rituximab Plus MTX36.28± 8.43
Course 1: FU Week 16 (n=160)
GroupValue95% CI
Rituximab Plus MTX37.23± 8.34
Course 1: FU Week 24 (n=161)
GroupValue95% CI
Rituximab Plus MTX37.94± 8.64
Course 1: FU Month 9 (n=74)
GroupValue95% CI
Rituximab Plus MTX37.28± 9.61
Course 1: FU Month 12 (n=39)
GroupValue95% CI
Rituximab Plus MTX36.92± 9.49
Course 2: FU Week 8 (n=102)
GroupValue95% CI
Rituximab Plus MTX37.27± 8.39
Course 2: FU Week 16 (n=105)
GroupValue95% CI
Rituximab Plus MTX38.34± 8.11
SF-36 MCS by Treatment Course Secondary · Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12

SF-36 was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and genera

Screening (n=171)
GroupValue95% CI
Rituximab Plus MTX44.04± 12.76
Course 1: FU Week 8 (n=165)
GroupValue95% CI
Rituximab Plus MTX45.32± 12.42
Course 1: FU Week 16 (n=160)
GroupValue95% CI
Rituximab Plus MTX45.06± 12.06
Course 1: FU Week 24 (n=161)
GroupValue95% CI
Rituximab Plus MTX45.18± 12.59
Course 1: FU Month 9 (n=74)
GroupValue95% CI
Rituximab Plus MTX44.35± 13.38
Course 1: FU Month 12 (n=39)
GroupValue95% CI
Rituximab Plus MTX41.95± 14.30
Course 2: FU Week 8 (n=102)
GroupValue95% CI
Rituximab Plus MTX45.94± 11.34
Course 2: FU Week 16 (n=105)
GroupValue95% CI
Rituximab Plus MTX45.99± 11.71
SF-36 Domain Scores by Treatment Course - Physical Functioning Secondary · Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12

SF-36 was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and genera

Screening (n=172)
GroupValue95% CI
Rituximab Plus MTX43.26± 24.74
Course 1: FU Week 8 (n=170)
GroupValue95% CI
Rituximab Plus MTX46.80± 25.20
Course 1: FU Week 16 (n=164)
GroupValue95% CI
Rituximab Plus MTX46.85± 25.16
Course 1: FU Week 24 (n=164)
GroupValue95% CI
Rituximab Plus MTX49.58± 26.45
Course 1: FU Month 9 (n=76)
GroupValue95% CI
Rituximab Plus MTX47.30± 26.17
Course 1: Follow-up Month 12 (n=39)
GroupValue95% CI
Rituximab Plus MTX46.92± 30.21
Course 2: FU Week 8 (n=105)
GroupValue95% CI
Rituximab Plus MTX47.17± 24.51
Course 2: FU Week 16 (n=106)
GroupValue95% CI
Rituximab Plus MTX49.03± 24.91
SF-36 Domain Scores by Treatment Course - Bodily Pain Secondary · Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12

SF-36 was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and genera

Screening (n=172)
GroupValue95% CI
Rituximab Plus MTX37.22± 18.00
Course 1: FU Week 8 (n=169)
GroupValue95% CI
Rituximab Plus MTX46.06± 20.62
Course 1: FU Week 16 (n=164)
GroupValue95% CI
Rituximab Plus MTX47.98± 22.29
Course 1: FU Week 24 (n=164)
GroupValue95% CI
Rituximab Plus MTX48.70± 21.39
Course 1: FU Month 9 (n=75)
GroupValue95% CI
Rituximab Plus MTX46.55± 25.29
Course 1: FU Month 12 (n=39)
GroupValue95% CI
Rituximab Plus MTX44.10± 25.24
Course 2: FU Week 8 (n=105)
GroupValue95% CI
Rituximab Plus MTX47.15± 20.93
Course 2: FU Week 16 (n=106)
GroupValue95% CI
Rituximab Plus MTX50.34± 21.60
SF-36 Domain Scores by Treatment Course - Physical Role Functioning Secondary · Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12

SF-36 was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and genera

Screening (n=173)
GroupValue95% CI
Rituximab Plus MTX45.85± 23.75
Course 1: FU Week 8 (n=170)
GroupValue95% CI
Rituximab Plus MTX50.04± 24.11
Course 1: FU Week 16 (n=166)
GroupValue95% CI
Rituximab Plus MTX51.28± 24.43
Course 1: FU Week 24 (n=165)
GroupValue95% CI
Rituximab Plus MTX52.92± 24.15
Course 1: FU Month 9 (n=76)
GroupValue95% CI
Rituximab Plus MTX49.51± 25.41
Course 1: FU Month 12 (n=39)
GroupValue95% CI
Rituximab Plus MTX47.44± 25.80
Course 2: FU Week 8 (n=103)
GroupValue95% CI
Rituximab Plus MTX52.79± 24.09
Course 2: FU Week 16 (n=106)
GroupValue95% CI
Rituximab Plus MTX53.54± 21.54
SF-36 Domain Scores by Treatment Course - Emotional Role Functioning Secondary · Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12

SF-36was assessed during follow-up at the specified timepoints following each course of treatment (participants could have received up to 3 courses of treatment with rituximab). The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and general

Screening (n=173)
GroupValue95% CI
Rituximab Plus MTX57.80± 27.52
Course 1: FU Week 8 (n=170)
GroupValue95% CI
Rituximab Plus MTX61.91± 26.27
Course 1: FU Week 16 (n=166)
GroupValue95% CI
Rituximab Plus MTX60.44± 28.06
Course 1: FU Week 24 (n=165)
GroupValue95% CI
Rituximab Plus MTX62.12± 26.87
Course 1: FU Month 9 (n=76)
GroupValue95% CI
Rituximab Plus MTX56.52± 28.52
Course 1: FU Month 12 (n=39)
GroupValue95% CI
Rituximab Plus MTX55.98± 30.82
Course 2: FU Week 8 (n=104)
GroupValue95% CI
Rituximab Plus MTX61.30± 25.41
Course 2: FU Week 16 (n=106)
GroupValue95% CI
Rituximab Plus MTX62.74± 25.28

Adverse events — posted to ClinicalTrials.gov

Time frame: 12 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Rituximab Plus MTX
Serious: 47/193 (24%)
Deaths:

Serious adverse events (51 terms)

ReactionSystemRituximab Plus MTX
Rheumatoid arthritisMusculoskeletal and connective tissue disorders
PneumoniaInfections and infestations
Respiratory tract infectionInfections and infestations
ArthritisMusculoskeletal and connective tissue disorders
Intervertebral disc protrusionMusculoskeletal and connective tissue disorders
OsteoarthritisMusculoskeletal and connective tissue disorders
Breast cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Coronary artery diseaseCardiac disorders
BronchitisInfections and infestations
GangreneInfections and infestations
Localised infectionInfections and infestations
NasopharyngitisInfections and infestations
Urinary tract infectionInfections and infestations
Femoral neck fractureInjury, poisoning and procedural complications
Hip fractureInjury, poisoning and procedural complications
LacerationInjury, poisoning and procedural complications
Radius fractureInjury, poisoning and procedural complications
Hepatic enzyme increasedInvestigations
Back painMusculoskeletal and connective tissue disorders
BursitisMusculoskeletal and connective tissue disorders
Muscular weaknessMusculoskeletal and connective tissue disorders
Rheumatoid noduleMusculoskeletal and connective tissue disorders
SynovitisMusculoskeletal and connective tissue disorders
Cervix carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Other adverse events (170 terms — click to expand)

ReactionSystemRituximab Plus MTX
NasopharyngitisInfections and infestations
BronchitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
DiarrhoeaGastrointestinal disorders
GastroenteritisInfections and infestations
Respiratory tract infectionInfections and infestations
CoughRespiratory, thoracic and mediastinal disorders
Infusion related reactionGeneral disorders
HypertensionVascular disorders
NauseaGastrointestinal disorders
RhinitisInfections and infestations
Back painMusculoskeletal and connective tissue disorders
DepressionPsychiatric disorders
GastritisGastrointestinal disorders
FatigueGeneral disorders
Oral herpesInfections and infestations
SinusitisInfections and infestations
HeadacheNervous system disorders
RashSkin and subcutaneous tissue disorders
InfluenzaInfections and infestations
ContusionInjury, poisoning and procedural complications
EpistaxisRespiratory, thoracic and mediastinal disorders
VertigoEar and labyrinth disorders
Abdominal pain upperGastrointestinal disorders
Acute tonsillitisInfections and infestations
CystitisInfections and infestations
Herpes zosterInfections and infestations
Tinea pedisInfections and infestations
Urinary tract infectionInfections and infestations
OsteoarthritisMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
Dermatitis allergicSkin and subcutaneous tissue disorders
EczemaSkin and subcutaneous tissue disorders
HyperhidrosisSkin and subcutaneous tissue disorders
AnaemiaBlood and lymphatic system disorders
ConjunctivitisEye disorders
Abdominal painGastrointestinal disorders
VomitingGastrointestinal disorders
ChillsGeneral disorders
Oedema peripheralGeneral disorders

Most-reported serious reactions: Rheumatoid arthritis, Pneumonia, Respiratory tract infection, Arthritis, Intervertebral disc protrusion, Osteoarthritis, Breast cancer, Coronary artery disease.

Data from ClinicalTrials.gov NCT00502840 adverse events section.

Sponsor's own description

This single arm study will evaluate the efficacy and safety of repeated courses of MabThera in patients with active rheumatoid arthritis who have participated in ML19070, and have completed the week 24 visit. Eligible patients (DAS28 \>2.6 after week 24), will receive 2 infusions of 1g MabThera (Day 1 and day 15). For all patients in this extension study, up to 3 repeated courses of treatment are allowed. The anticipated time on study treatment is 1-2 years, and the target sample size is 100-500 individuals.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.

Verify or expand the search:

Other trials of rituximab [MabThera/Rituxan]

Trials testing the same drug.

Other recruiting trials for Rheumatoid Arthritis

Currently open trials in the same condition.

Other Hoffmann-La Roche trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00502840.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing