A Non-Comparative Study to Assess the Safety of MabThera (Rituximab) in Patients With Rheumatoid Arthritis.
- Conditions
- Rheumatoid Arthritis
- Interventions
- Registration Number
- NCT00502996
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This single arm study will assess the safety of MabThera plus methotrexate in patients with rheumatoid arthritis who have had a lack of response to 1-5 DMARDs or biological agents. Patients will receive MabThera (1g i.v.) on days 1 and 15, concomitantly with methotrexate \>=15mg p.o./week. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 246
- adult patients, >=18 years of age;
- rheumatoid arthritis >=6 months;
- lack of response to 1-5 DMARDs or biological agents;
- rheumatoid factor positive.
- other chronic inflammatory articular disease or systemic rheumatic disease;
- joint or bone surgery during 8 weeks prior to randomization;
- previous treatment with any cell-depleting therapy.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Rituximab rituximab [MabThera/Rituxan] Eligible participants receiving Rituximab (MabThera/Rituxan) 1 gram/dose (g/dose) intravenously (IV) on Day 1 and Day 15 followed by previous pre-medication (methylprednisolone 100 mg IV, antihistamine and antipyretic) and concomitant treatment of Methotrexate at least 15 mg per oris (PO) weekly were observed during the study period of 24 weeks. After treatment completion, participants were followed-up for safety up to 24 weeks. Rituximab Methotrexate Eligible participants receiving Rituximab (MabThera/Rituxan) 1 gram/dose (g/dose) intravenously (IV) on Day 1 and Day 15 followed by previous pre-medication (methylprednisolone 100 mg IV, antihistamine and antipyretic) and concomitant treatment of Methotrexate at least 15 mg per oris (PO) weekly were observed during the study period of 24 weeks. After treatment completion, participants were followed-up for safety up to 24 weeks.
- Primary Outcome Measures
Name Time Method Number of Participants With Any Adverse Event, Any Serious Adverse Event, and Death Up to Week 48 An Adverse event (AE) was considered any unfavorable medical event in a participant of clinical research who received the study drug and that not necessarily had a causal relationship with this treatment. An AE could, therefore, being any unfavorable sign and non-intentional, symptom or disease temporarily related with the use of a medicinal product, considered or not related to the medicinal product. Pre-existing conditions that worsened during the study were reported as AEs. A serious adverse event (SAE) is any experience that suggested a significant risk, contraindication, caution, and at any dose fulfills at least one of the following criteria: adverse event considered as fatal (resulting in death), life threatening, defect of birth/congenital abnormality, required hospitalization or extension of hospital length of stay, significant medical intervention, resulted in significant disability/impairment.
Number of Participants With AEs According to Degree of Intensity Up to Week 48 An AE is any unfavorable sign and non-intentional, symptom or disease temporarily related with the use of a medicinal product, considered or not related to the medicinal product. Pre-existing conditions that worsened during the study were reported as AEs. The Intensity of AEs was classified as Grade 1, Grade 2, Grade 3 and Grade 4. Grade 1: Discomfort was noticed, but the normal daily activity was not interrupted. Grade 2: Discomfort was enough to reduce the normal daily activity. Grade 3: There was disability for work or develop normal daily activities. Grade 4: It represented an immediate threat to life (these events were reported as SAEs).
Number of Participants With AEs Leading to Discontinuation and Any Drug Related AEs and SAEs Up to Week 48 An AE is any unfavorable sign and non-intentional, symptom or disease temporarily related with the use of a medicinal product, considered or not related to the medicinal product. Pre-existing conditions that worsened during the study were reported as AEs. A SAE is any experience that suggested a significant risk, contraindication, caution, and at any dose, fulfills, at least, one of the following criteria: adverse event considered as fatal (resulting in death), life threatening, defect of birth/congenital abnormality, required hospitalization or extension of hospital length of stay, significant medical intervention, resulted in significant disability/impairment. Relationship between AEs and medication under investigation was evaluated through the classification "Yes" and "No". A relationship classified as "Yes" implied a significant causal relationship with the medication under investigation which was evaluated based on enough evidences, facts or arguments.
Number of Participants With AEs of Special Interest During the Study Screening (Days -28 to 0), EOT (Week 24), and EOFU (Week 48) Adverse event of special interest during the study treatment and follow up period included infections. The participants with AEs of special interest were reported at Screening, End of treatment (EOT), and End of Follow-up (EOFU) visit.
- Secondary Outcome Measures
Name Time Method Mean Values of Cholesterol, Uric Acid, Urea, Creatinine, Calcium, Total Bilirubin and Serum Total Proteins at Screening and EOT Visit. Screening (Days -28 to 0) and EOT (Week 24) The mean concentration of cholesterol, uric acid, urea, creatinine, calcium, total bilirubin and serum total proteins (STP) for each participant was estimated at Screening and at EOT visit.
Mean Duration of Morning Joint Stiffness Screening ((Days -28 to 0), EOT (Week 24), and EOFU (Week 48) The efficacy of rituximab was assessed by evaluating mean duration of morning joint stiffness.
Mean Value of Painful Joints Screening (Days -28 to 0), EOT (Week 24), and EOFU (Week 48) The efficacy of rituximab was assessed by evaluating painful joints.
Number of Participants With American College of Rheumatology (20, 50, and 70) Criteria Week 1, Week 12, and Week 24 American College of Rheumatology (ACR) criteria improvement consisting of 20%, 50%, and 70% (ACR20, ACR50, and ACR70, respectively) reduction in tender joints and swollen joints, as well as for three of the additional five ACR core set variables: patient's assessment of pain using a Visual Analog Scale (VAS) with left end of the line 0=no pain to right end of the line 100=unbearable pain); patient's global assessment of disease activity and physician's global assessment of disease activity using a VAS (0=no disease activity to 100=maximum disease activity); health assessment questionnaire (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; C-reactive protein and globular sedimentation velocity.
Mean Values of Potassium, Chlorine, Sodium, and Phosphorus at Screening and EOT Visit Screening (Days -28 to 0) and EOT (Week 24) The mean concentration of potassium, chlorine, sodium and phosphorus for each participant was estimated at Screening and at EOT.
Mean Values of C Reactive Protein Screening ((Days -28 to 0), EOT (Week 24), and EOFU (Week 48) C Reactive Protein (CRP) is a component of ACR. CRP is a marker of inflammation.
Mean Values of Globular Sedimentation Velocity Screening ((Days -28 to 0), Week 1, Week 12, and Week 24 Globular sedimentation velocity is a component of ACR.
Mean Values of Hematology Parameters at Screening and EOT Visit (Hemoglobin and Mean Corpuscular Hemoglobin Concentration) Screening (Days -28 to 0) and EOT (Week 24) The values of hemoglobin (Hb) and mean corpuscular hemoglobin concentration (MCHC) for each participant were estimated at Screening and at EOT visit.
Mean Values of Biochemistry Parameters at Screening and Visit 8 (Albumin and Glucose) Screening (Days -28 to 0) and EOT (Week 24) The mean albumin and glucose concentration for each participant was estimated at Screening and at EOT visit.
Mean Values of Hematology Parameters at Screening and EOT Visit (Hematocrit, Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils) Screening (Days -28 to 0) and EOT (Week 24) The hematology parameters (hematocrit, neutrophils, lymphocytes, monocytes, eosinophils, and basophils) for each participant were estimated at Screening and at EOT.
Mean Values of Hematology Parameters at Screening and EOT Visit (Leucocytes and Platelets) Screening (Days -28 to 0) and EOT (Week 24) The mean leucocytes and platelets concentration for each participant was estimated at Screening, at EOT visit.
Mean Values of Pain and Activity Based on Visual Analogue Scale Screening ((Days -28 to 0), Week 1, Week 12, and Week 24 Pain assessment was assessed by using a VAS (0=no pain to 100=unbearable pain). Disease activity was also evaluated by participants and investigators by using a VAS (0=no disease activity to 100=maximum disease activity).
Mean Values of Hematology Parameter at Screening and EOT Visit (Mean Corpuscular Volume) Screening (Days -28 to 0) and EOT (Week 24) Mean corpuscular volume (MCV) is the average volume of red cells. The mean MCV concentration for each participant was estimated at Screening and EOT.
Mean Values of Hematology Parameter at Screening and EOT Visit (Erythrocytes) Screening (Days -28 to 0) and EOT (Week 24) The mean erythrocyte concentration for each participant was estimated at Screening and at EOT.
Mean Values of Aspartate Transaminase, Alanine Transaminase, Alkaline Phosphatase, and Lactic Dehydrogenase at Screening and EOT Visit Screening (Days -28 to 0) and EOT (Week 24) The mean aspartate transaminase (AST) and alanine transaminase (ALT), Alkaline phosphatase (AP), and Lactic dehydrogenase (LDH) concentration for each participant was estimated at Screening and at EOT visit.
Mean Value of Quality of Life (Health Assessment Questionnaire - Disease Index) Screening (Days -28 to 0), Week 1, Week 12, and Week 24 Health Assessment Questionnaire - Disease Index (HAQ-DI) indicates how the disease affected participant's activities of daily life. It consisted of 20 questions in 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities) rated on a 4-point scale, 0=without any difficulty to 3=unable to do. Sum of scores was divided by number of domains with a score for a total possible score of 0 (best/no difficulties to perform activities) to 3 (worst/ unable to perform activities at all).
Mean Value of Inflamed Joints Screening (Days -28 to 0), EOT (Week 24), and EOFU (Week 48) The efficacy of rituximab was assessed by evaluating inflamed joints.