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

• ClinicalTrials.gov Identifier: NCT02079532
• Recruitment Status: Completed
• First Posted: March 5, 2014
• Results First Posted: June 9, 2015
• Last Update Posted: July 29, 2016
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

This study will evaluate the efficacy and safety of MabThera in patients with active rheumatoid arthritis who have had an inadequate response to one prior anti-TNF alpha inhibitor. MabThera-naive patients will be stratified into 3 arms, according to previous inadequate response to a)etanercept, b)infliximab or c)adalimumab. Patients will be treated with MabThera (1g infusion) on day 1 and day 15, and will continue their basic methotrexate therapy. The anticipated time on study treatment is 2+ years, and the target sample size is 100-500 individuals.

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Drug: rituximab [MabThera]	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 302 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Study to Evaluate the Safety of MabThera, and Its Effect on Treatment Response, in Patients With Rheumatoid Arthritis Following Inadequate Response to a Single Anti-TNF Agent
• Study Start Date: November 2006
• Actual Primary Completion Date: November 2010
• Actual Study Completion Date: November 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: MabThera (Rituximab)	Drug: rituximab [MabThera]; 1 g was given by intravenous infusion on Days 1 and 15

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline to Week 24 in Disease Activity Score Based on 28-Joint Count (DAS28) [ Time Frame: Week 24 ]
   The DAS28 consists of swollen joint count (SJC) and tender joint count (TJC) measurements, the erythrocyte sedimentation rate (ESR) in millimeters per hour (mm/hr), and the Patient's Global Assessment of Disease Activity (participant-ated rheumatoid arthritis [RA] 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 greater than (>)3.2 to 5.1 = moderate to high disease activity.

Secondary Outcome Measures :

1. DAS28 Score [ Time Frame: Screening and Weeks 8, 16, and 24 ]
   The DAS28 consists of SJC and TJC measurements, the ESR in mm/hr, and the Patient's Global Assessment of Disease Activity (participant-rated RA assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 ≤3.2 = low disease activity, DAS28 >3.2 to 5.1 = moderate to high disease activity.
2. Percentage of Participants With European League Against Rheumatism (EULAR) Response of Good or Moderate [ Time Frame: Weeks 8, 16, and 24 ]
   The DAS28-based EULAR response criteria were used to measure individual responses as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders experienced a change from baseline of >1.2 with a DAS28 score ≤3.2 and moderate responders experienced a change from baseline >1.2 with DAS28 >3.2 to ≤5.1 or a change from baseline >0.6 to ≤1.2 with a DAS28 score of ≤5.1.
3. Percentage of Participants With Low Disease Activity (DAS28 ≤3.2) at Week 24 [ Time Frame: Week 24 ]
   Percentage of participants with low disease activity defined as DAS28 ≤3.2 at follow-up Week 24. The DAS28 consists of SJC and TJC measurements, the ESR in mm/hr, and the Patient's Global Assessment of Disease Activity (participant rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity).
4. Percentage of Participants Achieving Remission (DAS28 <2.6) at Week 24 [ Time Frame: Week 24 ]
   Percentage of participants with remission defined as DAS28 <2.6 at follow-up Week 24. The DAS28 consists of SJC and TJC measurements, the ESR in mm/hr, and the Patient's Global Assessment 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 ≤3.2 = low disease activity, DAS28 >3.2 to 5.1 = moderate to high disease activity.
5. Percentage of Participants Achieving a Response By EULAR Category [ Time Frame: Weeks 8, 16, and 24 ]
   Percentage of participants achieving a response by EULAR category, including 'moderate', 'good', or no response at follow-up Weeks 8, 16, and 24. 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 of >3.2 to ≤5.1 or a change from baseline >0.6 to ≤1.2 with a DAS28 score of ≤5.1; non-responders had a change from baseline ≤0.6 or change from baseline >0.6 and ≤1.2 with a DAS28 score of >5.1.
6. Health Assessment Questionnaire - Disability Index (HAQ-DI) Score [ Time Frame: Screening and Weeks 8, 16, and 24 ]
   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. The standard disability score was calculated from the 8 categories by dividing the sum of the individual categories by the number of categories answered, yielding a score from 0 (without any difficulty) to 3 (unable to do).
7. Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score [ Time Frame: Screening and Weeks 8, 16, and 24 ]
   The FACIT fatigue scale is base on a 13-item questionnaire to assess the therapy-induced fatigue. Participants were requested to score each question on a scale ranging from 0 (best) to 4 (worst). The scoring system of the FACIT fatigue scale adds up to a total scale ranging from 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.
8. Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS) [ Time Frame: Screening and Weeks 8, 16, and 24 ]
   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.
9. SF-36 Domain Scores [ Time Frame: Screening and Weeks 8, 16, and 24 ]
   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 two 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.
10. Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Response (ACR20/ACR50/ACR70) [ Time Frame: Weeks 8, 16, and 24 ]
    ACR20/50/70 response: ≥20%, ≥50%, or ≥70% improvement, respectively, in tender or swollen joint counts and ≥20%, ≥50%, or ≥70% improvement, respectively, 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) participant assessment of functional disability via a HAQ-DI, and 5) C-reactive protein or ESR at each visit.
11. Swollen Joint Count (SJC) [ Time Frame: Screening and Weeks 8, 16, and 24 ]
    The 28 joints to be assessed for tenderness and 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, each, ranged from 0 to 28 with 0 as best possible health status and 28 as worst health status.
12. Tender Joint Count (TJC) [ Time Frame: Screening and Weeks 8, 16, and 24 ]
    The 28 joints to be assessed for tenderness and 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 tender joints ranged from 0 to 28 with 0 as best possible health status and 28 as worst health status.
13. Physician's Global Assessment of Disease Activity [ Time Frame: Screening and Weeks 8, 16, and 24 ]
    Physicians assessed the disease (RA) 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).
14. Patient's Assessment of Disease Activity [ Time Frame: Screening and Weeks 8, 16, and 24 ]
    Participants were to assess the disease (RA) 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).
15. Patient's Assessment of Pain [ Time Frame: Screening and Weeks 8, 16, and 24 ]
    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".
16. C-Reactive Protein (CRP) [ Time Frame: Screening, Days 1 and 15, and Weeks 8, 16, and 24 ]
    Mean CRP as measured as an acute phase reactant by mg per deciliter (mg/dL) at screening, Days 1 and 15, and Weeks 8, 16, and 24.
17. Erythrocyte Sedimentation Rate (ESR) [ Time Frame: Screening, Days 1 and 15, and Weeks 8, 16, and 24 ]
    Mean ESR, as an acute phase reactant, measured in mm/hr at screening, Days 1 and 15, and Weeks 8, 16, and 24.
18. Rheumatoid Factor (RF) [ Time Frame: Screening and Weeks 8, 16, and 24 ]
    Mean RF as measured by international unit per milliliter (IU/mL) at screening and Weeks 8, 16, and 24.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• adult patients, 18-75 years of age;
• rheumatoid arthritis for >=6 months;
• previous inadequate response to a single anti-TNF alpha inhibitor;
• methotrexate at a stable dose range 7.5-25 mg/week.

Exclusion Criteria:

• other chronic inflammatory articular disease or systemic autoimmune disease;
• previous treatment with MabThera or intolerance to MabThera;
• corticosteroids>=10 mg/day prednisolone within last 2 weeks, or corticosteroids at unstable doses within last 2 weeks;

Contacts and Locations

Locations

Germany

Bad Abbach, Germany, 93077

Bad Aibling, Germany, 83043

Bad Bramstedt, Germany, 24576

Bamberg, Germany, 96047

Berlin, Germany, 10117

Berlin, Germany, 12200

Berlin, Germany, 13055

Berlin, Germany, 13125

Berlin, Germany, 13589

Berlin, Germany, 14163

Bonn, Germany, 53111

Bremen, Germany, 28199

Cuxhaven, Germany, 27476

Damp, Germany, 24351

Donaueschingen, Germany, 78166

Dresden, Germany, 01109

Düsseldorf, Germany, 40211

Düsseldorf, Germany, 40225

Erfurt, Germany, 99096

Erlangen, Germany, 91054

Erlangen, Germany, 91056

Essen, Germany, 45239

Essen, Germany, 45326

Frankfurt Am Main, Germany, 60590

Freiburg, Germany, 79106

Fulda, Germany, 36039

GIEßEN, Germany, 35392

Gommern, Germany, 39245

Göttingen, Germany, 37075

Hagen, Germany, 58135

Halle, Germany, 06120

Hamburg, Germany, 22081

Hannover, Germany, 30159

Hannover, Germany, 30625

Heidelberg, Germany, 69120

Herne, Germany, 44652

Hofheim, Germany, 65719

Homburg/saar, Germany, 66424

Jena, Germany, 07743

Karlsruhe, Germany, 76135

Köln, Germany, 50924

Ludwigshafen, Germany, 67063

Mainz, Germany, 55122

Mainz, Germany, 55131

Mittelherwigsdorf, Germany, 02763

Muenchen, Germany, 80336

Mönchengladbach, Germany, 41061

München, Germany, 80335

München, Germany, 81541

Münster, Germany, 48149

Naunhof, Germany, 04683

Oldenburg, Germany, 26121

Osnabrück, Germany, 49074

Pirna, Germany, 01796

Ratingen, Germany, 40882

Rostock, Germany, 18059

Schwerte, Germany, 58239

Sendenhorst, Germany, 48324

Stuttgart, Germany, 70178

Treuenbrietzen, Germany, 14929

Trier, Germany, 54292

Tübingen, Germany, 72076

ULM, Germany, 89081

Wiesbaden, Germany, 65189

Wiesbaden, Germany, 65191

Wuerzburg, Germany, 97080

Wuppertal, Germany, 42105

Würselen, Germany, 52146

Zeven, Germany, 27404

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Chair: Clinical Trials; Hoffmann-La Roche

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02079532
• Other Study ID Numbers: ML19070
• First Posted: March 5, 2014
• Results First Posted: June 9, 2015
• Last Update Posted: July 29, 2016
• Last Verified: June 2016

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Rituximab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents