A randomized, double-blind, parallel group, international study to evaluate the safety and efficacy of ocrelizumab in combination with methotrexate (MTX) compared to MTX alone in methotrexate- naïve patients with active rheumatoid arthritis.
- Conditions
- Rheumatoid arthritis
- Registration Number
- EUCTR2006-005353-30-AT
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 600
Men and women =18 years old, with active RA of at least 3 months and less than 5 years duration who are naive to methotrexate (MTX)
Patients must meet the following criteria to be eligible for study
entry:
1. Ability and willingness to provide written informed consent and to comply with the requirements of the protocol
2. Age =18 years
3. Have active disease defined as: A) Diagnosis of RA of at least 3 months and less than 5 years duration using the ACR criteria for the classification of RA. B) Swollen joint count (SJC) =8 (66 joint count) and tender joint count (TJC) =8 (68 joint count) at screening and baseline. C) CRP =1.0 mg/dL using a high-sensitivity assay. D) Positive rheumatoid factor or positive anti-CCP antibody or both.
4. Previous and current treatments: A) Patients naïve to and considered to be candidates for treatment with MTX. B) Patients who are to receive, or who are currently receiving treatment for RA on an outpatient basis. C) If receiving current treatment with corticosteroids, the dose must not exceed 10 mg/day prednisolone or equivalent and during the four weeks prior to baseline it must be at a stable dose. D) If receiving current treatment with NSAIDs, the patient must be on a stable dose for the 4 weeks prior to baseline. E) Patient must be willing to receive oral folic acid or equivalent.
5. Other:
A) For patients of reproductive potential (males and females), a reliable means of contraception must be used for the duration of the study (e.g., hormonal contraceptive, intrauterine device, physical barrier) according to local guidelines. B) Female patients of childbearing age must have a negative urine pregnancy test.
Are the trial subjects under 18? no
Number of subjects for this age range:
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 Related to Rheumatoid Arthritis
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). Patients with secondary Sjögren’s syndrome or secondary limited cutaneous vasculitis with RA are eligible.
2. Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis (Appendix 3)
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. systemic lupus erythematosus, inflammatory bowel disease, scleroderma, inflammatory myopathy, mixed connective tissue disease or other overlap syndrome)
Exclusions Related to General Health
4. Any surgical procedure, including bone or joint surgery/synovectomy (including joint fusion or replacement) within 12 weeks prior to or planned within 48 weeks after baseline
5. Sepsis in a prosthetic joint within the last 48 weeks or indefinitely if the prosthesis concerned remains in situ
6. Lack of peripheral venous access
7. Pregnancy or breast feeding
8. Known significant cardiac disease (NYHA Class III and IV)
9. Known severe chronic obstructive pulmonary disease (COPD; [FEV1 < 50% predicted or Functional dyspnoea =Grade 3 on the MRC Dyspnoea Scale]
10. Evidence of significant uncontrolled concomitant diseases such as nervous system, renal, hepatic, endocrine, or gastrointestinal disorders which, in the investigator’s opinion, would preclude patient participation
11. Any neurological (congenital or acquired), psychiatric, 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, chronic fatigue syndrome, chronic remitting anemia of unknown origin or requiring transfusion)
12. Uncontrolled disease states where flares are commonly treated with oral or parenteral corticosteroids
13. Primary or secondary immunodeficiency (history of, or currently active), including known history of HIV infection
14. Known active infection of any kind (excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with iv anti-infectives within 4 weeks of baseline or oral anti-infectives within 2 weeks prior to baseline
15. History of deep space/tissue infection (e.g. fasciitis, abscess, osteomyelitis, septic arthritis of a native joint) within 48 weeks of baseline
16. Evidence of chronic active Hepatitis B or C
17. Evidence of active tuberculosis (patients receiving chemoprophylaxis for latent tuberculosis infection are eligible for the study)
18. History of serious recurrent or chronic infections not specified above
19. History of cancer within the last 10 years, including solid tumors and haematologic malignancies and carcinoma in situ (except basal cell and squamous cell carcinomas of the skin or carcinoma in situ of the cervix uteri that have been excised and cured)
20. Currently active alcohol or drug abuse or history of alcohol or drug abuse within 24 weeks prior to baseline
Exclusion Criteria Related to Medications
21. History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of ocrelizumab infusion
22. Prior receipt of any biologic therapy used for tre
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the efficacy of ocrelizumab versus placebo, when used in combination with methotrexate (MTX), to reduce or inhibit progression of joint damage in MTX-naïve patients.;Secondary Objective: •To assess the efficacy of ocrelizumab to prevent disability<br>•To determine the efficacy of ocrelizumab versus placebo, in<br>combination with methotrexate (MTX) in reducing signs and symptoms<br>•To assess the safety of ocrelizumab versus placebo, in<br>combination with MTX<br>•To investigate the pharmacokinetics, immunogenicity and<br>pharmacodynamic parameters of ocrelizumab<br>•To explore the long-term efficacy and safety of further<br>courses of ocrelizumab<br>;Primary end point(s): The treatment difference in change from baseline of the modified total Sharp score (TSS) at 52 Weeks.
- Secondary Outcome Measures
Name Time Method