|E.1 Medical condition or disease under investigation
|E.1.1||Medical condition(s) being investigated ||
|E.1.2 Medical condition or disease under investigation
|E.1.2||Classification code ||10039073
|E.1.2||Term ||Rheumatoid arthritis
|E.1.3||Condition being studied is a rare disease || No
|E.2 Objective of the trial
|E.2.1||Main objective of the trial ||
|To determine the efficacy of ocrelizumab versus placebo,
when used in combination with MTX, to reduce or inhibit
progression of joint damage in MTX-naïve patients.
|E.2.2||Secondary objectives of the trial ||
| To assess the efficacy of ocrelizumab to prevent disability in
To determine the efficacy of ocrelizumab versus placebo, in
combination with MTX in reducing signs and symptoms in
To assess the safety of ocrelizumab versus placebo, in
combination with MTX.
To investigate the pharmacokinetics, immunogenicity and
pharmacodynamic parameters of ocrelizumab in this patient
To explore the long-term efficacy and safety of further
courses of ocrelizumab.
|E.2.3||Trial contains a sub-study || Information not present in EudraCT
|E.3||Principal inclusion criteria ||
|Patients must meet the following criteria to be eligible for study
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
c. CRP >= 1.0 mg/dL using a high-sensitivity assay.
d. Positive rheumatoid factor or positive anti-CCP antibody
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
e. Patient must be willing to receive oral folic acid or
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.
|E.4||Principal exclusion criteria||
|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
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
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
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 treatment of
23. Concurrent treatment with any DMARD. All DMARDs
should be withdrawn at least 4 weeks prior to baseline
(12 weeks for leflunomide or 4 weeks after 11 days of
standard cholestyramine or activated charcoal drug removal).
|E.5 End points
|E.5.1||Primary end point(s)||
|The treatment difference in change from baseline of the modified total Sharp Score (TSS) at 52 weeks.
|E.6 and E.7 Scope of the trial
|E.6||Scope of the trial
|E.6.9||Dose response|| Yes
|E.6.10||Pharmacogenetic|| Information not present in EudraCT
|E.6.13||Others|| Information not present in EudraCT
|E.7||Trial type and phase
|E.7.1||Human pharmacology (Phase I)|| No
|E.7.1.1||First administration to humans|| No
|E.7.1.2||Bioequivalence study|| No
|E.18.104.22.168||Other trial type description||
|E.7.2||Therapeutic exploratory (Phase II)|| No
|E.7.3||Therapeutic confirmatory (Phase III)|| Yes
|E.7.4||Therapeutic use (Phase IV)|| No
|E.8 Design of the trial
|E.8.1.3||Single blind|| No
|E.8.1.4||Double blind || Yes
|E.8.1.5||Parallel group|| Yes
|E.8.1.6||Cross over || No
|E.8.2|| Comparator of controlled trial
|E.8.2.1||Other medicinal product(s)|| No
|E.8.2.2||Placebo || Yes
|combination with MTX vs MTX
The trial involves single site in the Member State concerned
|E.8.4|| The trial involves multiple sites in the Member State concerned || Yes
|E.8.5||The trial involves multiple Member States|| Yes
|E.8.6 Trial involving sites outside the EEA
|E.8.6.1||Trial being conducted both within and outside the EEA|| Yes
|E.8.6.2||Trial being conducted completely outside of the EEA|| Information not present in EudraCT
|E.8.6.3||If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned||
|E.8.7||Trial has a data monitoring committee|| Information not present in EudraCT
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|E.8.9.1||In the Member State concerned years||6
|E.8.9.1||In the Member State concerned months||0
|E.8.9.1||In the Member State concerned days||
|E.8.9.2||In all countries concerned by the trial years||6
|E.8.9.2||In all countries concerned by the trial months||0