A randomised, double-blind, international study to evaluate the efficacy and safety of various re-treatment regimens of rituximab in combination with methotrexate in RA patients with an inadequate response to methotrexate.

• Register: EUCTR
• Last refreshed on: 14 October 2013
• Main ID: EUCTR2005-002396-33-IT
• Date of registration: 01/03/2006
• Prospective Registration: No
• Primary sponsor: F. Hoffmann- La Roche Ltd.
• Public title: A randomised, double-blind, international study to evaluate the efficacy and safety of various re-treatment regimens of rituximab in combination with methotrexate in RA patients with an inadequate response to methotrexate.
• Scientific title: A randomised, double-blind, international study to evaluate the efficacy and safety of various re-treatment regimens of rituximab in combination with methotrexate in RA patients with an inadequate response to methotrexate.
• Date of first enrolment: 30/11/2005
• Target sample size: 375
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-002396-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Number of treatment arms in the trial: 3

Countries of recruitment

Finland, Germany, Hungary, Italy, Slovakia, Spain, United Kingdom

Contacts

• Name: Clinical Operations
• Affiliation: Roche S.p.A.

• Name: Clinical Operations
• Affiliation: Roche S.p.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Able and willing to give written informed consent and comply with the requirements of the study protocol. 2. Patients with rheumatoid arthritis for at least 6 months, diagnosed according to the revised 1987 ACR criteria for the classification of rheumatoid arthritis. 3. Receiving treatment on an outpatient basis. 4. Swollen joint count (SJC) ≥ 8 (66 joint count), and tender joint count (TJC) ≥ 8 (68 joint count) at screening and baseline. 5. At screening, either CRP ≥ 0.6 mg/dL (6 mg/L) OR ESR ≥ 28 mm/h. 6. Minimum age 18 years. 7. Glucocorticoids ≤ 10 mg/day prednisolone or equivalent permitted if stable for at least 4 weeks prior to baseline. 8. Use of NSAIDs is permitted if stable for at least 2 weeks prior to baseline. 9. For patients of reproductive potential (males and females), use of a reliable means of contraception (e.g. hormonal contraceptive, patch, intrauterine device, physical barrier) throughout study participation. Protocol WA17044 - 4 TARGET POPULATION (Cont.) 10. Must have an inadequate response to MTX and have been receiving and tolerating this at a dose of 10-25 mg/wk (p.o. or parenteral) for at least 12 weeks, with the last 4 weeks prior to baseline at a stable dose. MabThera (Rituximab) (Re-treatment should occur within 2 weeks. If more than 4 weeks elapses the patient is required to be reassessed for eligibility) Entry criterion for absolute neutrophil count (not below 1.5 × 103/μL) was met at the last blood sample analysis. Patient has not developed contra-indications for receiving rituximab, such as: a) Any new or uncontrolled concomitant disease such as, but not limited to cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders. For patients who have entered the study and have been found to be HBsAg negative, HBcAb positive negative hepatitis B viral DNA (<29 IU/mL) and AST/ALT ≤2.5× ULN results within the last 12 weeks.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA (including but not limited to vasculitis, pulmonary fibrosis or Felty s syndrome). Secondary Sjogren s syndrome or secondary limited cutaneous vasculitis with RA is permitted. 2. Functional class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis. 3. History of, or current, inflammatory joint disease other than RA (e.g., gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease) or other systemic autoimmune disorder (e.g., SLE, inflammatory bowel disease, scleroderma, inflammatory myopathy, mixed connective tissue disease or other overlap syndrome). 4. Diagnosis of juvenile idiopathic arthritis (JIA) or juvenile rheumatoid arthritis (JRA) and/or RA before age 16. Exclusions Related to General Health 5. Any surgical procedure, including bone/joint surgery/ Synovectomy (including joint fusion or replacement) within 12 weeks prior to baseline or planned within 48 weeks of randomization. 6. Lack of peripheral venous access. 7. Pregnancy or lactation. 8. Significant cardiac or pulmonary disease (including obstructive pulmonary disease). 9. Evidence of significant uncontrolled concomitant disease such as nervous system, renal, hepatic, endocrine or gastrointestinal disorders which, in the investigator s opinion, would preclude patient participation. 10. Primary or secondary immunodeficiency (history of, or currently active), including known history of HIV infection. 11. Known active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with i.v. anti-infectives within 4 weeks of baseline or oral anti-infectives within 2 weeks prior to baseline. 12. History of deep space/tissue infection (e.g. fasciitis, abscess, osteomyelitis) within 52 weeks of baseline. 13. History of serious recurrent or chronic infection (to check for chest infection a chest x-ray will be performed at screening if not performed within 12 weeks of screening). 14. History of cancer, including solid tumors, hematologic malignancies and carcinoma in situ (except basal cell and squamous cell carcinoma of the skin that have been excised and cured). Protocol WA17044 - 5 TARGET POPULATION (Cont.) 15. Any neurological (congenital or acquired), vascular or systemic disorder which could affect any of the efficacy assessments, in particular, joint pain and swelling (e.g. Parkinson s disease, cerebral palsy, diabetic neuropathy). 16. Currently active alcohol or drug abuse or history of alcohol or drug abuse within 24 weeks prior to baseline.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Rheumatoid Arthritis
MedDRA version: 14.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Trade Name: Mabthera
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Rituximab
Concentration unit: mg milligram(s)
Concentration number: 500-

Primary Outcome(s)

Main Objective: To determine if a second course with an increased dose of rituximab is associated with improved responses compared to re-treatment with the same dose.

Primary end point(s): Proportion of patients with an ACR20 response at Week 48.

Secondary Objective: 2. To determine response rates to two courses of 2 × 500 mg rituximab and two courses of 2 × 1000 mg rituximab. 3. To investigate the pharmacokinetics of rituximab associated with 2 courses of treatment.

Secondary ID(s)

WA17044

2005-002396-33-ES

Source(s) of Monetary Support

F.Hoffmann-La Roche Ltd.