Rheumatoid arthritis MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis
Conditions
Interventions
Product Name: ocrelizumab
Product Code: RO 496-4913/F03
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ocrelizumab
CAS Number: 637334-45-3
Current Sponsor code: RO 496
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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. Current treatment for RA on an outpatient basis 4. Active disease, defined as the following: a. A diagnosis of RA using the American College of Rheumatology (ACR) criteria for RA. b. Swollen joint count (SJC) = 4 (66 joint count) and tender joint count (TJC) = 4 (68 joint count) at screening and baseline c. C-reactive protein (CRP) = 0.6 mg/dL using a high-sensitivity assay or erythrocyte sedimentation rate (ESR) = 28 mm/hour d. Positive rheumatoid factor or positive anti-cyclic citrullinated peptide (CCP) antibody, or both 5. Inadequate clinical response to MTX taken at a dose of 7.5-25 mg/week for at least 12 weeks, with the last 4 weeks prior to baseline at a stable dose 6. The patient must be willing to receive oral folic acid or equivalent. Previous and current treatments (beyond MTX) may include the following: 7. If the patient is receiving current treatment with corticosteroids, the dose must not exceed 10 mg/day of prednisolone or equivalent, and, during the 4 weeks prior to baseline, it must be at a stable dose and remain stable for the duration of the study. 8. If the patient is receiving current treatment with NSAIDs, the patient must be on a stable dose for the 4 weeks prior to baseline and remain stable for the duration of the study. 9. May have experienced an inadequate response to previous or current treatment with other DMARDs and biologics such as etanercept, infliximab, adalimumab, or abatacept because of toxicity or inadequate efficacy. 10. 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. 11. 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
Exclusion criteria: Exclusion criteria related to RA: 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 RA. 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) Exclusion criteria 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 lactation 8. Known significant cardiac disease (New York Heart Association [NYHA] Class III and IV). 9. Known severe chronic obstructive pulmonary disease (COPD) (forced expiratory volume in 1 second [FEV1] < 50% predicted or functional dyspnea Grade= 3 on the Medical Research Council [MRC] Dyspnea Scale). 10. Evidence of significant uncontrolled concomitant diseases 11. Any neurological (congenital or acquired), psychiatric, vascular, or systemic disorder that could affect any of the efficacy assessments; in particular, joint pain and swelling 12. Uncontrolled disease states where flares are commonly treated with oral or parenteral corticosteroids 13. History of, or currently active, primary or secondary immunodeficiency 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 intravenous (IV) anti-infectives within 4 weeks prior to baseline or oral anti-infectives within 2 weeks prior to baseline 15. History of deep space/tissue infection (e.g., fasciitis, abscess, osteomyelitis, or 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 hematologic 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. Concurrent treatment with any DMARD except MTX. All DMARDs except MTX should be withdrawn at least 4 weeks prior to baseline (8 weeks for infliximab, adalimumab, or abatacept; 4 weeks for etanercept; and 12 weeks for leflunomide or 4 weeks after 11 days of standard cholestyramine or a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary endpoint for this study is the proportion of patients with ACR20 responses at 24 weeks.;Main Objective: Primary Objectives The primary objective of this study is to determine the efficacy and safety of 400 mg ocrelizumab, given as a single infusion, versus placebo, in combination with MTX, to reduce the signs and symptoms of RA at 24 weeks in patients with active RA who currently have an inadequate response to MTX therapy.;Secondary Objective: Secondary Objectives Secondary objectives for this study are as follows: • To investigate and compare the pharmacokinetics and pharmacodynamics of a single and a dual infusion of ocrelizumab in this patient population • To assess the effect of a single infusion of ocrelizumab versus placebo on physical function in this patient population • To compare the safety and efficacy of single versus dual infusion at 24 and 48 weeks | — |
Countries
France, Germany, Italy, Spain, United Kingdom
Outcome results
None listed