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A Study of the Efficacy and Safety of Re-treatments With Rituximab in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Anti-tnfa Therapies

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02097745
First Posted: March 27, 2014
Last Update Posted: November 3, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Biogen
Information provided by (Responsible Party):
Hoffmann-La Roche
  Purpose
This study will assess the long-term safety and efficacy of repeating treatment with MabThera, in combination with methotrexate and steroids, in patients who were previously randomized into MabThera study WA17042. The anticipated time on study treatment is until Mabthera is available on the local market and the target sample size is 100-500 individuals.

Condition Intervention Phase
Rheumatoid Arthritis Drug: methotrexate Drug: rituximab [MabThera/Rituxan] Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label Study of the Efficacy and Safety of Re-treatments With Rituximab (MabThera/Rituxan) in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Anti-TNFa Therapies

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With an American College of Rheumatology 20 (ACR20) Response [ Time Frame: Baseline to the end of the retreatment period (up to 7 years, 6 months) ]
    A patient had an ACR20 response if there was at least a 20% improvement, ie, reduction from Baseline, in tender and swollen joint counts (28 assessed joints) and in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, left end=no disease activity [symptom-free and no arthritis symptoms], right end=maximum disease activity; patient assessment of pain in previous 24 hours on a VAS (left end=no pain and right end=unbearable pain); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and acute-phase reactant (either C-reactive protein or erythrocyte sedimentation rate). The ACR20 response was compared to Baseline in the precursor study WA17042. The first retreatment may have occurred in the precursor study WA17042.


Secondary Outcome Measures:
  • Change From Baseline in the Disease Activity Score 28 (DAS28) [ Time Frame: Baseline to the end of the retreatment period (up to 7 years, 6 months) ]
    The DAS28 is an index for measuring disease activity in rheumatic arthritis and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where a higher score represents higher disease activity. A negative change score indicates improvement. The first retreatment may have occurred in the precursor study WA17042.

  • Percentage of Participants With DAS28 Low Disease Activity and DAS28 Remission [ Time Frame: Baseline to the end of the retreatment period (up to 7 years, 6 months) ]
    The DAS28 is an index for measuring disease activity in rheumatic arthritis and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. Low disease activity was defined as a DAS28 score ≤ 3.2. DAS28 remission was defined as a DAS28 score < 2.6. The first retreatment may have occurred in the precursor study WA17042.

  • Percentage of Participants With Good, Moderate, or no European League Against Rheumatism (EULAR) Responses [ Time Frame: Baseline to the end of the retreatment period (up to 7 years, 6 months) ]
    Change of the Disease Activity Score 28 score from baseline was used to determine EULAR responses of good, moderate, or no response. For a post-baseline score ≤ 3.2, a change from baseline of < -1.2 was a good response, < -0.6 to ≥ -1.2 was a moderate response, and ≥ -0.6 was no response. For a post-baseline score > 3.2 to ≤ 5.1, a change from baseline of < -0.6 was a moderate response and ≥ -0.6 was no response. For a post-baseline score > 5.1, a change from baseline < -1.2 was a moderate response and ≥ -1.2 was no response. A good response could not be achieved for post-baseline scores > 3.2. The first retreatment may have occurred in the precursor study WA17042.

  • Change From Baseline in the American College of Rheumatology n (ACRn) Response [ Time Frame: Baseline to the end of the retreatment period (up to 7 years, 6 months) ]
    The ACRn response was defined as each participant's least favorable percentage change from Baseline in 3 measures, tender joint count, swollen joint count (28 assessed joints), and improvement score achieved in at least 3 of the 5 remaining ACR parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, left end=no disease activity, right end=maximum disease activity; patient assessment of pain in previous 24 hours on a VAS (left end=no pain, right end=unbearable pain); Health Assessment Questionnaire-Disability Index (20 questions, 8 components, 0=without difficulty to 3=unable to do); and acute-phase reactant (either C-reactive protein or erythrocyte sedimentation rate). A higher change percentage indicates greater improvement from Baseline. The ACRn response was compared to Baseline in the precursor study WA17042. The first retreatment may have occurred in the precursor study WA17042.

  • Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score [ Time Frame: Baseline to the end of the retreatment period (up to 7 years, 6 months) ]
    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.

  • Change From Baseline in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey [ Time Frame: Baseline to the end of the retreatment period (up to 7 years, 6 months) ]
    The SF-36 Health Survey uses patient-reported symptoms on 8 subscales to assess health-related quality of life (HRQoL). The Physical Component Summary (PCS) score summarizes the subscales Physical Functioning, Role-Physical, Bodily Pain, and General Health. The Mental Component Summary (MCS) score summarizes the subscales Vitality, Social Functioning, Role-Emotional, and Mental Health. Each score was scaled from 0 to 100 with a higher score indicating better HRQoL. A positive change score indicates an improvement in HRQoL.

  • Change From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score [ Time Frame: Baseline to the end of the retreatment period (up to 7 years, 6 months) ]
    The FACIT-F is a 13-item participant self-reporting questionnaire that assesses fatigue over the previous 7 days by scoring each item on a 5-point scale (0=Not at all, 1=A little bit, 2=Somewhat, 3=Quite a bit, 4=Very much). An overall FACIT-F score was obtained by summing the scores of all 13 items. The overall score ranged from 0 to 52. A lower score indicates less fatigue. A negative change score indicates improvement.

  • Percentage of Participants With no Radiographic Progression From Baseline to Year 5 [ Time Frame: Baseline to Year 5 ]
    Radiographic progression was defined as a change of ≤ 0 in the total Genant-modified Sharp score. The Genant-modified Sharp scoring system assesses structural damage due to rheumatoid arthritis in radiographs. A score for erosions of 0-3.5 (8 gradations) is assigned for 14 joints in each hand and wrist, and 6 joints in each foot. Joint space narrowing scores of 0-4 (9 gradations) are assigned to 13 joints in each hand and 6 joints in each foot. The maximum erosion score is 40 x 3.5 = 140. The maximum joint space narrowing score is 38 x 4.0 = 152. Both the erosion and joint space narrowing scores are normalized to 145 and are added together for a maximum total Genant-modified Sharp score of 290; the minimum score is 0. A higher score indicates more damage. Data is reported for 2 groups.

  • Change From Baseline in the Total Genant-modified Sharp Score at Year 5 [ Time Frame: Baseline to Year 5 ]
    The Genant-modified Sharp scoring system assesses structural damage due to rheumatoid arthritis in radiographs. A score for erosions of 0-3.5 (8 gradations) is assigned for 14 joints in each hand and wrist, and 6 joints in each foot. Joint space narrowing scores of 0-4 (9 gradations) are assigned to 13 joints in each hand and 6 joints in each foot. The maximum erosion score is 40 x 3.5 = 140. The maximum joint space narrowing score is 38 x 4.0 = 152. Both the erosion and joint space narrowing scores are normalized to 145 and are added together for a maximum total Genant-modified Sharp score of 290; the minimum score is 0. A higher score indicates more damage. A negative change score indicates improvement. Data is reported for 2 groups.

  • Change From Baseline in the Genant-modified Sharp Erosion Score at Year 5 [ Time Frame: Baseline to Year 5 ]
    The Genant-modified Sharp scoring system assesses structural damage due to rheumatoid arthritis in radiographs. A score for erosions of 0-3.5 (8 gradations) is assigned for 14 joints in each hand and wrist, and 6 joints in each foot. The maximum erosion score is 40 x 3.5 = 140 which is normalized to 145. The minimum score is 0 and the maximum score is 145. A higher score indicates more damage. A negative change score indicates improvement. Data is reported for 2 groups.

  • Change From Baseline in the Genant-modified Sharp Joint Space Narrowing Score at Year 5 [ Time Frame: Baseline to Year 5 ]
    The Genant-modified Sharp scoring system assesses structural damage due to rheumatoid arthritis in radiographs. A score joint space narrowing of 0-4 (9 gradations) is assigned to 13 joints in each hand and 6 joints in each foot. The maximum joint space narrowing score is 38 x 4.0 = 152 which is normalized to a score of 145. The minimum score is 0 and the maximum score is 145. A higher score indicates more damage. A negative change score indicates improvement. Data is reported for 2 groups.

  • Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Year 5 [ Time Frame: Baseline to Year 5 ]
    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. Data is reported for 2 groups.


Enrollment: 341
Study Start Date: June 2004
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MabThera/Rituxan Drug: methotrexate
a 10-25 mg stable dose given orally or parenterally throughout study
Drug: rituximab [MabThera/Rituxan]
1 g given by intravenous infusion on Days 1 and 15 of each treatment course
Other Name: MabThera/Rituxan

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • adult patients 18-80 years of age with active RA;
  • patients who participated in MabThera study WA17042, and completed to at least the Week 24 visit;
  • eligible for re-treatment, based on clinical symptoms;
  • patients of reproductive potential must be using reliable contraceptive methods.

Exclusion Criteria:

  • patients who participated in MabThera study WA17042 but withdrew into the safety follow-up;
  • current treatment with any other disease-modifying antirheumatic drug (apart from methotrexate), or any anti-TNFalfa, anti-IL1, or other biologic therapies;
  • development of any new contraindications to receiving MabThera;
  • women who are pregnant or breast-feeding.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02097745


  Show 97 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Biogen
Investigators
Study Chair: Clinical Trials Hoffmann-La Roche
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02097745     History of Changes
Obsolete Identifiers: NCT00468377
Other Study ID Numbers: WA17531
First Submitted: March 20, 2014
First Posted: March 27, 2014
Results First Submitted: October 8, 2014
Results First Posted: November 7, 2014
Last Update Posted: November 3, 2016
Last Verified: September 2016

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Rituximab
Methotrexate
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Nucleic Acid Synthesis Inhibitors