E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
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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 |
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. |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
FARMACOGENETICA: Versione: Data: Titolo:Farmacogenetica (RSR) Obiettivi:
ALTRI SOTTOSTUDI: - Genotipizzazione clinica; - Marcatori biologici (BSR)
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E.3 | Principal inclusion criteria |
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 (see Appendix 1, ~xr1i ). 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. |
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E.4 | Principal 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 Feltys syndrome). Patients with secondary Sjögrens 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 (see Appendix 3, ~xr3i ). 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. Note that minor skin surgeries and dental procedures are allowed if they are completely resolved and have not resulted in any complications. 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 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 such as nervous system, renal, hepatic, endocrine, or gastrointestinal disorders that, in the investigators opinion, would preclude patient participation. 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 (e.g., Parkinsons disease, cerebral palsy, diabetic neuropathy, chronic fatigue syndrome, or chronic remitting anemia of unknown origin or requiring transfusion) Etc. (including Exclusion criteria related to medications and Exclusion criteria related to laboratory values at screening) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients with ACR20 responses at 24 weeks |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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.7.1.3 | Other | No |
E.7.1.3.1 | 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 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
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.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Previsto periodo di estensione in aperto. |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
dose in singola infusione rispetto a doppia inf. |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
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 |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |