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.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00502840
First received: July 17, 2007
Last updated: September 3, 2014
Last verified: September 2014

July 17, 2007
September 3, 2014
July 2007
September 2011   (final data collection date for primary outcome measure)
Change From Baseline in DAS28 Score at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
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.
Change of DAS28 in week 24 achieved by re-treatment. Change from course specific baseline and original course baseline.
Complete list of historical versions of study NCT00502840 on ClinicalTrials.gov Archive Site
  • DAS28 Score by Treatment Course and Follow-up (FU) Visit [ Time Frame: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12 ] [ Designated as safety issue: No ]
    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.
  • Percentage of Participants With European League Against Rheumatism (EULAR) Response of 'Good' or 'Moderate' by Treatment Course [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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 ≤5.1.
  • Percentage of Participants Achieving a Response By EULAR Category and Treatment Course [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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 score ≤5.1; non-responders had a change from baseline ≤0.6 or change from baseline >0.6 and ≤1.2 with a DAS28 score > 5.1.
  • Health Assessment Questionnaire - Disability Index (HAQ-DI) Score by Treatment Course [ Time Frame: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12 ] [ Designated as safety issue: No ]
    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 standard disability score was calculated from the 8 categories by dividing the sum of the individual categories by the number of categories answered ;total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. The questionnaire was provided in a German translation and was scored based on the instructions from the Stanford University Medical Center.
  • Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score by Treatment Course [ Time Frame: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12 ] [ Designated as safety issue: No ]
    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 calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (best) to 52 (worst). The assessment was originally developed for chronic illnesses and is now validated for patients with rheumatoid arthritis (RA). The questionnaire was provided in a German translation.
  • Short-Form 36 (SF-36) Physical Composite Scores (PCS) by Treatment Course [ Time Frame: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12 ] [ Designated as safety issue: No ]
    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 general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the PCS and mental composite t-score (MCS). The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.
  • SF-36 MCS by Treatment Course [ Time Frame: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12 ] [ Designated as safety issue: No ]
    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 general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the PCS and MCS. The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.
  • SF-36 Domain Scores by Treatment Course - Physical Functioning [ Time Frame: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12 ] [ Designated as safety issue: No ]
    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 general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the PCS and MCS. The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.
  • SF-36 Domain Scores by Treatment Course - Bodily Pain [ Time Frame: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12 ] [ Designated as safety issue: No ]
    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 general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the PCS and MCS. The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.
  • SF-36 Domain Scores by Treatment Course - Physical Role Functioning [ Time Frame: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12 ] [ Designated as safety issue: No ]
    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 general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the physical and mental composite t-scores (PCS and MCS). The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.
  • SF-36 Domain Scores by Treatment Course - Emotional Role Functioning [ Time Frame: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12 ] [ Designated as safety issue: No ]
    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 health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the physical and mental composite t-scores (PCS and MCS). The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.
  • SF-36 Domain Scores by Treatment Course - Emotional Well-Being [ Time Frame: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12 ] [ Designated as safety issue: No ]
    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 general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the PCS and MCS. The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.
  • SF-36 Domain Scores by Treatment Course - Social Functioning [ Time Frame: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12 ] [ Designated as safety issue: No ]
    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 general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the PCS and MCS. The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.
  • SF-36 Domain Scores by Treatment Course - Vitality [ Time Frame: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12 ] [ Designated as safety issue: No ]
    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 general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the PCS and MCS. The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.
  • SF-36 Domain Scores by Treatment Course - General Heath Perceptions [ Time Frame: Screening, FU Weeks 8, 16, and 24, and FU Months 9 and 12 ] [ Designated as safety issue: No ]
    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 general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the PCS and MCS. The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.
  • Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Percent (%), 50%, or 70% Improvement (ACR20/ACR50/ACR70) by Treatment Course [ Time Frame: 24 weeks after each course ] [ Designated as safety issue: No ]
    ACR 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). ACR20/50/70 response: ≥20/50/70%, respectively, improvement in SJC or TJC and 20/50/70% improvement in 3 of the following 5 criteria: 1) Physician's Global Assessment of Disease Activity, 2) Patient's Global Assessment of Disease Activity, 3) Patient's Assessment of Pain, 4) participants assessment of functional disability via HAQ-DI, and 5) C-reactive protein (CRP) or ESR at each visit.
  • Swollen Joint Count [ Time Frame: Screening and Week 24 ] [ Designated as safety issue: No ]
    Mean sum of 28 swollen joints 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 28 joints to be assessed for swelling were shoulder, elbow, wrist, metacarpophalangeal (MCP) joints 1-5, proximal interphalangeal (PIP) joints 1-5, and knee on both sides of the body. The sum of swollen joints ranged from 0 to 28 with 0 as best possible health status and 28 as worst health status.
  • Tender Joint Count [ Time Frame: Screening and Week 24 ] [ Designated as safety issue: No ]
    Mean sum of 28 tender joints 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 28 joints to be assessed for tenderness were shoulder, elbow, wrist, MCP joints 1-5, PIP joints 1-5, and knee on both sides of the body. The sum of tender joints ranged from 0 to 28 with 0 as best possible health status and 28 as worst health status.
  • Physician's Global Assessment of Disease Activity [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    Physician's Global Assessment of Disease Activity 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). Baseline was defined as the original baseline score from assessment performed in Study ML19070. Physicians were to assess the disease activity on a 100-mm horizontal VAS. The left-hand extreme of the line (0 mm) was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right hand extreme (100 mm) as "maximum disease activity" (maximum arthritis disease activity).
  • Patient's Global Assessment of Disease Activity [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    Patient Global Assessment of Disease Activity 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). Baseline was defined as the original baseline score from assessment performed in Study ML19070. Participants were to assess the disease activity on a 100-mm horizontal VAS. The left-hand extreme of the line (0 mm) was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right hand extreme (100 mm) as "maximum disease activity" (maximum arthritis disease activity).
  • Patient's Assessment of Pain [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    Patient Assessment of Pain 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). Baseline was defined as the original baseline score from assessment performed in Study ML19070. Participants were to assess their current level of pain on a 100 mm horizontal VAS. The left-hand extreme of the line (0 mm) was described as "no pain" and the right-hand (100 mm) as "unbearable pain".
  • C-Reactive Protein [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    CRP measured in milligrams per deciliter (mg/dL) 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). Baseline was defined as the original baseline score from assessment performed in Study ML19070.
  • Erythrocyte Sedimentation Rate [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    ESR mean scores measured in mm/hr at 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). Baseline was defined as the original baseline score from assessment performed in Study ML19070.
  • Rheumatoid Factor (RF) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    RF measured in international units per milliliter (IU/mL) 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). Baseline was defined as the original baseline score from assessment performed in Study ML19070.
Efficacy: ACR 20/50/70, HAQ, SF-36, FACIT-F, TJC, SJC, CRP, BSG, RF achieved in week 24 by re-treatment. Safety: AEs.
Not Provided
Not Provided
 
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.
An Open Label Study to Evaluate the Safety of Re-treatment With MabThera, and Its Effect on Treatment Response, in Patients With Rheumatoid Arthritis Following Inadequate Response to a Single Anti-TNF Agent (Extension Study to ML19070).

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.

Not Provided
Interventional
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Rheumatoid Arthritis
Drug: rituximab [MabThera/Rituxan]
1g iv on days 1 and 15
Experimental: 1
Intervention: Drug: rituximab [MabThera/Rituxan]
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
193
September 2011
September 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • adult patients with rheumatoid arthritis who participated in ML19070, and have completed the week 24 visit;
  • eligible for re-treatment (DAS28 >2.6 after week 24, swollen joint count >=4, tender joint count >=4).

Exclusion Criteria:

  • patients who have withdrawn from treatment in ML19070 pre-week 16;
  • patients with a previous response in DAS28 <0.6 to MabThera after week 16;
  • concurrent treatment with any DMARD except for methotrexate, any TNF alpha inhibitor, or other biologic or investigational agent.
Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT00502840
ML19071
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP