A Study of MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Failed on One Prior Anti-TNF Therapy (RESET)

This study has been completed.
Sponsor:
Information provided by:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01272908
First received: January 7, 2011
Last updated: July 8, 2014
Last verified: July 2014
  Purpose

This study will evaluate the safety and effectiveness of MabThera (rituximab) in patients with active rheumatoid arthritis who are receiving methotrexate, and who have a previous or current inadequate response to one prior anti-TNF therapy. All patients will receive MabThera 1000 mg as an intravenous infusion on days 1 and 15. After the initial study phase of 24 weeks, eligible patients may receive one re-treatment with MabThera. The anticipated time on study treatment is 48 weeks.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: rituximab
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Rituximab Phase IIIb Open-label, Multi-centre Assessment of Safety and Effectiveness in Patients With RA Following an Inadequate Response to One Prior Anti-TNF Inhibitor (RESET)

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Adverse Events During the Initial Treatment Period - Overall Summary [ Time Frame: Days 1, 2, 15, and 16 and Week 48 of Initial treatment period ] [ Designated as safety issue: No ]
    Percentage of participants who reported an AE or serious AE (SAE), a drug-related AE, who had an acute infusion reaction, an AE leading to study drug discontinuation, with an infection or serious infection, or who died.


Secondary Outcome Measures:
  • Percentage of Participants With Adverse Events During the Re-Treatment Period - Overall Summary [ Time Frame: Days 1, 2, 15, and 16 and Week 48 of Re-treatment period ] [ Designated as safety issue: No ]
    Percentage of participants who reported an AE or SAE, a drug-related AE, who had an acute infusion reaction, an AE leading to study drug discontinuation, with an infection or serious infection, or who died.

  • Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period [ Time Frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period ] [ Designated as safety issue: No ]
    ACR20/50/70, defined as ≥20 percent (%), 50%, or 70% improvement, respectively, compared to baseline in tender joint count (TJC) and swollen joint count (SJC), and 20%/50%/70% improvement in at least 3 of 5 additional ACR core set variables: Patient Assessment of Pain; Patient's Global Assessment of Disease Activity; Physician's Global Assessment of Disease Activity; Health Assessment Questionnaire - Disability Index (HAQ-DI); and an acute phase reactant (erythrocyte sedimentation rate [ESR] or C-Reactive Protein [CRP]). If CRP was missing or not done, then ESR was used.

  • Percentage of Participants With Complete Clinical Response Per ACR Criteria During the Initial Treatment Period [ Time Frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period ] [ Designated as safety issue: No ]
    Complete clinical response was defined as having an ACR70 for at least 13 weeks.

  • Percentage of Participants Meeting ACR Response Criteria During the Re-treatment Period [ Time Frame: Weeks 12 and 24 of Re-treatment period ] [ Designated as safety issue: No ]
    ACR20/50/70, defined as ≥20%, 50%, or 70% improvement, respectively, compared to baseline in TJC and SJC, and 20%/50%/70% improvement in at least 3 of 5 additional ACR core set variables: Patient Assessment of Pain; Patient's Global Assessment of Disease Activity; Physician's Global Assessment of Disease Activity; HAQ-DI; and an acute phase reactant (ESR or CRP). If CRP was missing or not done, then ESR was used.

  • Percentage of Participants With Complete Clinical Response Per ACR Criteria During the Re-Treatment Period [ Time Frame: Weeks 12 and 24 of Re-treatment period ] [ Designated as safety issue: No ]
    Complete clinical response was defined as having an ACR70 for at least 13 weeks.

  • Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period [ Time Frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period ] [ Designated as safety issue: No ]
    The EULAR response criteria were based on the assessment of disease activity using the DAS28. The EULAR response criteria included not only change in disease activity but current disease activity. To be classified as responders, participants had to have a significant change in DAS28 and a low current disease activity. There were 4 categories of EULAR response rates: good, moderate, good/moderate, and none. The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score less than or equal to [≤]3.2), moderate (DAS28 score greater than [>]3.2 but ≤5.1), or high (DAS28 score >5.1). A DAS28 score <2.6 corresponded to a state of remission according to American Rheumatism Association criteria.

  • Percentage of Participants Meeting EULAR Response Criteria During the Re-Treatment Period [ Time Frame: Weeks 12 and 24 of Re-treatment period ] [ Designated as safety issue: No ]
    The EULAR response criteria were based on the assessment of disease activity using the DAS28. The EULAR response criteria included not only change in disease activity but current disease activity. To be classified as responders, participants had to have a significant change in DAS28 and a low current disease activity. There were 4 categories of EULAR response rates: good, moderate, good/moderate, and none. The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score >3.2 but ≤5.1), or high (DAS28 score >5.1). A DAS28 score <2.6 corresponded to a state of remission according to American Rheumatism Association criteria.

  • Change From Baseline in DAS28 During the Initial Treatment Period [ Time Frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period ] [ Designated as safety issue: No ]
    The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score >3.2 but ≤5.1), or high (DAS28 score >5.1). A DAS28 score <2.6 corresponded to a state of remission according to American Rheumatism Association criteria. A change of 1.2 units in DAS28 in an individual participant was considered a significant change.

  • Change From Baseline in DAS28 During the Re-Treatment Period [ Time Frame: Weeks 12 and 24 of Re-treatment period ] [ Designated as safety issue: No ]
    The DAS28 scoring used 4 core components: SJC, TJC, Patient Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score >3.2 but ≤5.1), or high (DAS28 score >5.1). A DAS28 score <2.6 corresponded to a state of remission according to American Rheumatism Association criteria. A change of 1.2 units in DAS28 in an individual participant was considered a significant change.

  • Change From Baseline in SJC During the Initial Treatment Period [ Time Frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period ] [ Designated as safety issue: No ]
    Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees.

  • Change From Baseline in SJC During the Re-Treatment Period [ Time Frame: Weeks 12 and 24 of Re-treatment period ] [ Designated as safety issue: No ]
    Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees.

  • Change From Baseline in TJC During the Initial Treatment Period [ Time Frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period ] [ Designated as safety issue: No ]
    Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees.

  • Change From Baseline in TJC During the Re-Treatment Period [ Time Frame: Weeks 12 and 24 of Re-treatment period ] [ Designated as safety issue: No ]
    Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees.

  • Change From Baseline in Physician's Global Assessment of Disease Activity During the Initial Treatment Period [ Time Frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period ] [ Designated as safety issue: No ]
    Physician Global Assessment of Disease Activity was measured using a 100-mm visual analog scale (VAS) where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity. The physician marked the line and the distance from the left edge was measured in mm.

  • Change From Baseline in Physician's Global Assessment of Disease Activity During the Re-Treatment Period [ Time Frame: Weeks 12 and 24 of Re-treatment period ] [ Designated as safety issue: No ]
    Physician Global Assessment of Disease Activity was measured using a 100-mm VAS where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity. The physician marked the line and the distance from the left edge was measured in mm.

  • Change From Baseline in Patient Global Assessment of Disease Activity Score During the Initial Treatment Period [ Time Frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period ] [ Designated as safety issue: No ]
    Patient Global Assessment of Disease Activity was measured using a 100-mm VAS where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity. The participant was asked to marked the line and the distance from the left edge was measured in mm.

  • Change From Baseline in Patient Global Assessment of Disease Activity During the Re-Treatment Period [ Time Frame: Weeks 12 and 24 of Re-treatment period and Week 4 after last maintenance ] [ Designated as safety issue: No ]
    Patient Global Assessment of Disease Activity was measured using a 100-mm VAS where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity. The participant was asked to marked the line and the distance from the left edge was measured in mm.

  • Change From Baseline in Patient Global Assessment of Pain During the Initial Treatment Period [ Time Frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period ] [ Designated as safety issue: No ]
    Patient Global Assessment of Pain was measured using a 100-mm VAS where the extreme left end of the line was 0 = no pain and the extreme right end of the line was 100 = unbearable pain. The participant was asked to mark the line and the distance from the left edge was measured in mm.

  • Change From Baseline in Patient Global Assessment of Pain During the Re-Treatment Period [ Time Frame: Weeks 12 and 24 of Re-treatment period ] [ Designated as safety issue: No ]
    Patient Global Assessment of Pain was measured using a 100-mm VAS where the extreme left end of the line was 0 = no pain and the extreme right end of the line was 100 = unbearable pain. The participant was asked to mark the line and the distance from the left edge was measured in mm.

  • Change From Baseline HAQ-DI Score During the Initial Treatment Period [ Time Frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period ] [ Designated as safety issue: No ]
    HAQ-DI: 20 questions, 8 categories of functioning: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common usual activities. Participants report amount of difficulty in performing 2-3 specific subcategory items. Difficulty score is from 0 to 3 (0 = without any difficulty; 1 = with some difficulty; 2 = with much difficulty; and 3 = unable to do). The highest component score in each of the 8 categories determined the score for that category, unless aids, devices, and/or help from another person were required which = a score of 2 (unless already 2 or 3). The 8 category scores were averaged into overall HAQ-DI score ranging from 0 to 3 (0 to 1 = mild to moderate difficulty; 1 to 2 = moderate to severe disability; and 2 to 3 = severe to very severe disability). HAQ-DI not computed if > 2 categories were missing.

  • Change From Baseline HAQ-DI Score During the Re-Treatment Period [ Time Frame: Weeks 12 and 24 of Re-treatment period ] [ Designated as safety issue: No ]
    HAQ-DI: 20 questions, 8 categories of functioning: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common usual activities. Participants report amount of difficulty in performing 2-3 specific subcategory items. Difficulty score is from 0 to 3 (0 = without any difficulty; 1 = with some difficulty; 2 = with much difficulty; and 3 = unable to do). The highest component score in each of the 8 categories determines the score for that category, unless aids, devices, and/or help from another person were required which = a score of 2 (unless already 2 or 3). The 8 category scores were averaged into overall HAQ-DI score ranging from 0 to 3 (0 to 1 = mild to moderate difficulty; 1 to 2 = moderate to severe disability; and 2 to 3 = severe to very severe disability). HAQ-DI not computed if >2 categories were missing.

  • Change From Baseline in ESR During the Initial Treatment Period [ Time Frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period ] [ Designated as safety issue: No ]
    ESR was measured in mm/hour and was used to determine the acute phase response. Lower ESR values indicate reduction in disease activity; normal reference range: 0-20 mm/hr.

  • Change From Baseline in ESR During the Re-Treatment Period [ Time Frame: Weeks 12 and 24 of Re-treatment period ] [ Designated as safety issue: No ]
    ESR was measured in mm/hour and was used to determine the acute phase response. Lower ESR values indicate reduction in disease activity; normal reference range: 0-20 mm/hr.

  • Change From Baseline in CRP During the Initial Treatment Period [ Time Frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period ] [ Designated as safety issue: No ]
    CRP levels were measured in milligrams/liter (mg/L) and were used to determine the acute phase response. A reduction in CRP levels is considered an improvement; normal reference range ≤10 mg/L.

  • Change From Baseline CRP During the Re-Treatment Period [ Time Frame: Weeks 12 and 24 of Re-treatment period ] [ Designated as safety issue: No ]
    CRP levels were measured in mg/L and were used to determine the acute phase response. A reduction in CRP levels is considered an improvement; normal reference range ≤10 mg/L.

  • Percentage of Participants With Disease Remission According to DAS28 in the Initial Treatment Period [ Time Frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period ] [ Designated as safety issue: No ]
    The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score >3.2 but ≤5.1), or high (DAS28 score >5.1). A DAS28 score ≤2.6 corresponded to a state of remission according to American Rheumatism Association criteria.

  • Percentage of Participants With Disease Remission According to DAS28 in the Re-Treatment Period [ Time Frame: Weeks 12 and 24 of Re-treatment period ] [ Designated as safety issue: No ]
    The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR. The DAS28 has a continuous scale ranging from 0 to 9.4. The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score >3.2 but ≤5.1), or high (DAS28 score >5.1). A DAS28 score ≤2.6 corresponded to a state of remission according to American Rheumatism Association criteria.

  • Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Score During the Initial Treatment Period [ Time Frame: Weeks 4, 12, 24, 36, and 48 of Initial treatment period ] [ Designated as safety issue: No ]
    Participant fatigue was evaluated using the FACIT-F scale, a 13-item questionnaire in which the participants were requested to score each item on a 5-point scale. The FACIT-F scores ranged from 0 to 52, with higher scores representing less fatigue. Score changes of 4 points or more were considered clinically meaningful. The total score was a summation of all 13 items, where 2 of the positive items (I have energy; I am able to do my usual activities) were reversed for scoring.

  • Change From Baseline in FACIT-F Total Score During the Re-Treatment Period [ Time Frame: Weeks 12 and 24 of Re-treatment period ] [ Designated as safety issue: No ]
    Participant fatigue was evaluated using the FACIT-F scale, a 13-item questionnaire in which the participants were requested to score each item on a 5-point scale. The FACIT-F scores ranged from 0 to 52, with higher scores representing less fatigue. Score changes of 4 points or more were considered clinically meaningful. The total score was a summation of all 13 items, where 2 of the positive items (I have energy; I am able to do my usual activities) were reversed for scoring.


Enrollment: 120
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single arm Drug: rituximab
1000 mg intravenously on Days 1 and 15

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients, 18-80 years of age
  • Moderate to severe active rheumatoid arthritis
  • Inadequate response to a single previous or current treatment with an anti-TNF agent
  • Methotrexate for at least 12 weeks, at a stable dose over the past 4 weeks

Exclusion Criteria:

  • Previous treatment with MabThera
  • Use of an anti-TNF agent within past 8 weeks (4 in the case of etanercept)
  • Concurrent treatment with any Disease Modifying Anti-Rheumatic Drug (DMARD) other than methotrexate
  • Active infection, or history of serious or chronic infection
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01272908

  Show 41 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Chair: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Disclosures Group, Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01272908     History of Changes
Other Study ID Numbers: ML20381
Study First Received: January 7, 2011
Results First Received: May 12, 2014
Last Updated: July 8, 2014
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Rituximab
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014