A Study of MabThera (Rituximab) in Combination With Methotrexate in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to Anti-TNF Therapies.

Rheumatoid Arthritis Clinical Trial

Official title:

An Open-label Study to Evaluate the Effect of MabThera in Combination With Methotrexate on Treatment Response in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Anti-TNF Therapies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00462345
• Other study ID #: ML20934
• Status: Completed
• Phase: Phase 4
• First received: April 18, 2007
• Last updated: October 30, 2014
• Start date: June 2007
• Est. completion date: July 2009

Study information

• Verified date: October 2014
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This single arm study will evaluate the efficacy and safety of MabThera in combination with methotrexate in patients with rheumatoid arthritis who have had an inadequate response to one or more anti-TNF therapies. Patients will receive MabThera 1000mg i.v. on days 1 and 15, and methotrexate (10-25mg/week p.o. or parenteral), together with methylprednisolone 100mg i.v. prior to infusion of MabThera. After week 24, eligible patients may receive re-treatment. The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• adult patients, 18-80 years of age;

• rheumatoid arthritis for >=6 months;

• receiving outpatient treatment;

• an inadequate response to at least one anti-TNF therapy;

• stable methotrexate for >=12 weeks.

Exclusion Criteria:

• other rheumatic autoimmune disease or inflammatory joint disease;

• previous treatment with MabThera;

• concurrent treatment with any DMARD (apart from methotrexate), anti-TNF alpha therapy, or other biologic agent.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• rituximab
1000 mg i.v. on Days 1 and 15
• Methotrexate
10 to 25 mg/week p.o. or parenteral from Day 1 through Week 24
• Corticosteroid or NSAID
=10 mg/day prednisone p.o., or equivalent corticosteroid, or NSAIDs p.o. from Day 1 through Week 24

Dietary Supplement:
• Folate
=5 mg/week, once daily or b.i.d. from Day 1 through Week 24

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With An American College of Rheumatology 20 Percent (%) Improvement Criteria (ACR20) Response at Week 24	ACR20 response: =20% improvement in tender joint count; =20% improvement in swollen joint count; and =20% improvement in at least 3 of 5 remaining ACR core measures: Patient Assessment of Pain; Patient Global Assessment of Disease Activity (PtGA); Physician Global Assessment of Disease Activity (PGA); self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ-DI]); and either C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR).	Week 24	No
Secondary	Percentage of Participants With An American College of Rheumatology 50% Improvement Criteria (ACR50) Response at Week 24	ACR50 response: =50% improvement in tender joint count; =50% improvement in swollen joint count; and =50% improvement in at least 3 of 5 remaining ACR core measures: Patient Assessment of Pain; PtGA; PGA; self-assessed disability (HAQ-DI); and either CRP or ESR.	Week 24	No
Secondary	Percentage of Participants With An American College of Rheumatology 70% Improvement Criteria (ACR70) Response at Week 24	ACR70 response: =70% improvement in tender joint count; =70% improvement in swollen joint count; and =70% improvement in at least 3 of 5 remaining ACR core measures: Patient Assessment of Pain; PtGA; PGA; self-assessed disability (HAQ-DI); and either CRP or ESR.	Week 24	No
Secondary	Disease Activity Score Based on 28-Joint Count (DAS-28)	DAS28 was calculated from the number of swollen joints and tender joints using the 28 joints count, the ESR (millimeters per hour [mm/hr]) and PtGA of disease activity with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 =3.2 equals (=) low disease activity, DAS28 greater than (>)3.2 to 5.1 = moderate to high disease activity.	Baseline and Week 24	No
Secondary	Percentage of Participants With Change in DAS-28 From BL to Week 24 of =1.2	DAS28 was calculated from the number of swollen joints and tender joints using the 28 joints count, the ESR (mm/hr) and PtGA of disease activity with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity.	Baseline, Week 24	No
Secondary	Percentage of Participants With DAS Response by European League Against Rheumatism (EULAR) Category at Week 24	The percentage of participants categorized as good, moderate, or nonresponders according to the EULAR response criteria at Week 24. Participants were categorized as good responders if the intensity of their symptoms was in the "low disease activity (DAS28 less than [<]3.2)" category after treatment, and their symptoms significantly decreased to >1.2. Participants were categorized as moderate responders if the intensity of their symptoms was in the "moderate or high disease activity (DAS28 >3.2)" category after treatment, and the symptoms significantly decreased to >1.2; or if the intensity of their symptoms was in the "low or moderate disease activity (DAS28 <5.1)" category, and the DAS28 score changed more than 0.6 or 1.2 or less. Participants were categorized as non-responders if they did not fall into the good or moderate categories.	Week 24	No
Secondary	Swollen Join Count (SJC)	Number of swollen joints was determined by examination of 66 joints (as assessed through pressing and palpating during the physical examination) and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit as swollen or not swollen.	Baseline, Weeks 24 and 48	No
Secondary	Tender Joint Count (TJC)	Number of tender joints was determined by examination of 68 joints (as assessed through pressing and palpating during the physical examination) and identifying when swelling was present. The number of tender joints was recorded on the joint assessment form at each visit as either tender or not tender.	Baseline, Weeks 24 and 48	No
Secondary	Patient Global Assessment of Disease Activity (VAS)	The mean score of the symptoms of rheumatoid arthritis (RA) at Week 0 (baseline) and the change from Week 0 to Weeks 24 and 48 as assessed by participants using a 100 mm horizontal VAS, where the left endpoint indicated "No disease activity" (no symptom, or no symptom of RA), and the right endpoint indicated "Maximum disease activity" (maximum RA activity). A negative change from Baseline indicated improvement.	Baseline, Weeks 24 and 48	No
Secondary	Physician Global Assessment of Disease Activity (VAS)	The mean score of the symptoms of RA at Week 0 and the change from Week 0 (baseline) to Weeks 24 and 48 as assessed by investigators using a 100-mm horizontal VAS, where the left endpoint indicated "No disease activity" (no symptom, or no symptom of RA), and the right endpoint indicated "Maximum disease activity" (maximum RA activity). A negative change from Baseline indicated improvement.	Baseline, Weeks 24 and 48	No
Secondary	Patient Assessment of Pain (VAS)	The mean score of pain at Week 0 (baseline) and the change from Week 0 to Weeks 24 and 48 as assessed by participants using a 100-mm horizontal VAS, where the left endpoint indicated "No pain," and the right endpoint indicated "Unbearable pain." A negative change indicated improvement.	Baseline, Weeks 24 and 48	No
Secondary	C-reactive Protein (CRP) Level	The mean level of CRP in milligrams per liter (mg/L), an acute phase reactant, at Week 0 and the change from Week 0 to Weeks 24 and 48.	Baseline, Weeks 24 and 48	No
Secondary	Erythrocyte Sedimentation Rate (ESR)	The mean level of ESR (in mm/hr), an acute phase reactant, at Week 0 and the change from Week 0 to Weeks 24 and 48.	Baseline, Weeks 24 and 48	No
Secondary	HAQ-DI Score	HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.	Baseline, Weeks 24 and 48	No
Secondary	Physical Function as Assessed by Short Form 36 (SF-36)	SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).	Screening, Weeks 24 and 48	No
Secondary	SF-36 Mental Component Scores	SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).	Screening, Weeks 24 and 48	No
Secondary	Modified Total Sharp-Genant Score (mTSS)	Posterior-anterior (PA) radiograph of each hand and anterior-posterior (AP) radiograph of each foot were taken separately and assessed according to Genant's method as modified from Sharp's method. The Sharp-Genant score=total of the erosion score and the joint space narrowing (JSN) score of all the hands and feet. Erosion Score: 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. JSN Score:13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). Maximum total erosion score in hands=100 and in feet=42; maximum scores for JSN in the hands=100 and in feet=48. Maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score. Change in scores was calculated as change=final score minus initial score.	Screening and Weeks 24 and 48	No
Secondary	Modified Sharp Radiographic Erosion Score (ES)	Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Maximum total erosion score in the hands was 100 and in the feet was 42, for a maximum overall score of 142. Total erosion score was for both hands and feet.	Screening, Weeks 24 and 48	No
Secondary	Modified Sharp Radiographic Joint Space Narrowing Score (JSN)	JSN Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). Maximum total scores for JSN in the hands was 100 and in the feet was 48, for a maximum overall score of 148. Total JSN was for both hands and feet.	Screening, Weeks 24 and 48	No