| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| 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 assess the efficacy of RO4402257 as monotherapy in adult patients with active RA. |
|
| E.2.2 | Secondary objectives of the trial |
To assess the safety profile of RO4402257 as monotherapy in RA patients.
To assess the efficacy and safety of several dose levels of RO4402257.
To collect sparse pharmacokinetic (PK) sampling data that can be combined with PK sampling data from other RO4402257 studies in order to investigate the PK profile of RO4402257 in the target RA patient population by a population analysis approach.
|
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
Able and willing to give written informed consent and to comply with the study protocol.
Active RA as diagnosed by the 1987 American College of Rheumatology (ACR; formerly American Rheumatism Association) criteria (Appendix 2).
Age greater than or equal to 18 years.
Receiving treatment for RA on an outpatient basis.
Swollen joint count (SJC) greater than or equal to 6 (66 joint count) and tender joint count (TJC) greater than or equal to 8 (68 joint count) at screening and baseline.
At screening, either high sensitivity C-reactive protein (hs-CRP) greater than or equal to 0.6 mg/dL (6 mg/L) or erythrocyte sedimentation rate (ESR) ≥ 28 mm/h or morning stiffness greater than or equal to 45 minutes.
Females of child-bearing potential and nonsterilized males with female partners of child-bearing potential only if willing to use a reliable means of contraception (e.g., physical barrier, contraceptive pill, patch, or IUD) during the study and for 4 weeks following the last dose of study drug.
If female and of childbearing potential, must have a negative pregnancy test within 3 weeks prior to randomization and at baseline (prior to administration of study drug on Day 1).
|
|
| E.4 | Principal exclusion criteria |
General -
Major surgery (including joint surgery) within 8 weeks prior to screening or planned surgery within 3 months after randomization.
Rheumatic autoimmune disease other than RA (including systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polymyositis) or significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis, Felty’s syndrome); Sjögren’s Syndrome with RA is allowed.
Bed-ridden or confined to a wheelchair.
Prior history of or current inflammatory joint disease other than RA (e.g., tophaceous gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease).
Exclusions for previous or concomitant medications -
Treatment with MTX within 8 weeks of baseline visit.
Discontinuation of previous MTX due to clinically important toxicity or insufficient efficacy at therapeutic doses as determined by the investigator.
Use of sulfasalazine, azathioprine, cyclosporine, thalidomide, D-penicillamine, hydroxychloroquine, chloroquine, gold, or tacrolimus within 3 weeks prior to baseline; use of leflunomide within 8 weeks (or 4 weeks after 11 days of standard cholestyramine washout) prior to baseline.
Corticosteroid dose greater than 10 mg/day prednisone (or equivalent, see Appendix 1).
Concurrent treatment with any DMARD, including anti-TNF or other biological therapy for RA.
Previous exposure to anti-TNF or anti-IL-1 therapies resulting in significant safety issues or lack of efficacy. Patients who stopped therapy due to cost or intolerance of infusions or injections are permitted but must have discontinued treatment prior to baseline as follows: etanercept > 2 weeks, infliximab or adalimumab > 8 weeks, anakinra > 2 weeks.
Treatment with another investigational agent within 6 weeks or 5 half-lives of screening, whichever is longer.
Previous treatment with any cell depleting therapies, including investigational agents (e.g., CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19, and anti-CD20); immunoabsorption columns within 6 months prior to baseline.
Previous treatment with alkylating agents.
Intraarticular or parenteral corticosteroids within 4 weeks prior to the baseline visit.
Exclusions for General Safety -
Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including asthma), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), or gastrointestinal disease.
History of malignancy, including solid tumors and hematologic malignancies (except basal cell carcinoma of the skin that has been excised and cured).
One of the following:
• History of active tuberculosis
• Chest x-ray findings consistent with active or latent tuberculosis
• Positive PPD (≥ 10 mm induration) unless there is a definite history of BCG immunization and the investigator ascertains that there is no recent history of tuberculosis exposure.
Known active bacterial (including mycobacterial), viral (including HIV), fungal, or other infections (excluding fungal infections of nail beds).
Any episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of baseline or oral antibiotics within 2 weeks prior to baseline.
History of hereditary or acquired immune deficiency disorder.
History of recurrent bacterial infections as an adult.
Immunization with a live vaccine within 4 weeks prior to baseline.
Pregnant women or nursing (breast feeding) mothers.
History of alcohol, drug or chemical abuse within the six months prior to screening.
Neuropathies or other painful conditions that might interfere with pain evaluation.
Laboratory Exclusions at Screening -
Screening alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 X ULN.
Screening calculated creatinine clearance < 50 mL/minute (for Cockroft-Gault equation, see Appendix 3).
Screening CPK > 2 x ULN.
Screening platelet count < 100,000 cells/mm3.
Screening hemoglobin < 9 g/dL.
Screening White Blood Cells < 3000 cells/mm3.
Positive Hepatitis B surface antigen or Hepatitis C antibody.
History of positive HIV antibody or HIV RNA above detectable level.
Measurement of the QTcB interval at screening greater than or equal to 450 msec.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy parameter is the proportion of patients with an ACR20 response at Week 12.
According to the American College of Rheumatology response criteria, achievement of an ACR20 response requires at least a 20% improvement, compared to baseline, in both tender and swollen joint counts, as well as in 3 out of the 5 following parameters: physician’s global assessment of disease activity, patient’s global assessment of disease activity, patient’s assessment of pain, HAQ, and an acute phase reactant, either hs-CRP or ESR.
Baseline is defined as the assessment immediately prior to the first administration of study drug (Day 1).
|
|
| 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 | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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.8.5 | 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 |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
Print
