E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with active rheumatoid arthritis |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
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 assess the effect of SSR150106XB 90 μg once daily and SSR150106XB 90 μg once every other day to reduce systemic inflammation in patients with active rheumatoid arthritis, as measured by changes in the acute phase protein, C-reactive protein, over a 4-week treatment period |
|
E.2.2 | Secondary objectives of the trial |
To assess the effect of SSR150106XB 90 μg once daily and SSR150106XB 90 μg once every other day to reduce systemic inflammation in patients with active rheumatoid arthritis, as measured by changes in acute phase protein, serum amyloid A (SAA) and cytokine interleukin-6 (IL-6), and clinical ACR20/ACR50/ACR70 % improvement responder rates (composite index) and for each of the individual index components, Disease Activity Score (DAS28-(CRP)), duration (hours/minutes) of morning stiffness over a 4-week treatment period
To assess the effect of SSR150106XB to reduce pain intensity in the early dosing period (Days 1-14), as assessed by changes from baseline in pain intensity on Visual Activity Scale (VAS).
To obtain evidence of the safety and tolerability of SSR150106XB in the treatment of patients with active rheumatoid arthritis.
To document plasma concentrations of SSR150106 and of the active metabolite SSR150655 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Diagnosis of RA for at least 6 months (ARA 1987)
For patients requiring discontinuation of exclusionary RA therapies at the pre-screening visit, active disease as defined by: At least 3 of the 68 joints assessed as painful or tender on motion At least 3 of the 66 joints assessed as swollen Morning stiffness of at least 30 minutes C-reactive protein (CRP) above the central laboratory’s upper limit of normal range OR erythrocyte sedimentation rate (ESR) greater than 28 mm/h.
For all patients at screening and baseline visits (at most 4 weeks apart), active disease as defined by: At least 9 of the 68 joints assessed as painful or tender on motion At least 6 of the 66 joints assessed as swollen Morning stiffness of at least 45 minutes
C-reactive protein (CRP) ≥1.8 mg/dL at screening
Non-PMs CYP2D6 Metabolizer status, confirmed by genotyping, prior to enrollment |
|
E.4 | Principal exclusion criteria |
Functional RA class IV (ACR 1991)
RA treatment failure with 3 or more established DMARDs, immunosuppressant and newer biologic agents
Previous treatment within the following time periods before first intake of investigational product (IP): Methotrexate - 6 weeks Hydroxychloroquine, sulfasalazine, gold salts, penicillamine, azathiaprine, cyclosporine mycophenylate mofetil - 4 weeks Leflunomide – 6 weeks Receptor antagonists: etanercept, anakinra, abatacept – 4 weeks Monoclonal antibodies – 12 weeks
Prior treatment with rituximab
Intra-articular corticosteroid injections less than 4 weeks before first intake of IP
Oral glucocorticoids greater than 10 mg prednisone (or equivalent) daily
Analgesics and NSAID/COX-2 inhibitor with daily dose(s) greater than approved for treatment of RA
Patients with conditions/concomitant diseases making them non-evaluable for the primary efficacy endpoint: Pain condition with etiology other than from RA History of an acute inflammatory joint disease other than RA
Refusal or inability to give informed consent
Patients likely to be non-compliant or unlikely to complete the study
Fever (oral temperature > 38oC), chronic infections or inter-current infections requiring antimicrobial therapy: previous or active infection with hepatitis B or C or other liver disease Known or suspected HIV/AIDs Past or current treatment for tuberculosis
History of multiple allergic reactions to drugs
Presence or history of cancer
Congenital or acquired immunodeficiency
Drug or alcohol abuse within 2 years of study entry
Have a history of significant other concomitant illness that could interfere with the patient’s participation in the study
Abnormal laboratory tests: Creatinine clearance < 30 cc/min AST > 2 X ULN ALT > 2 X ULN Alkaline phosphatase > 2 X ULN Conjugated bilirubin > 2 X ULN Complete blood count: Hemoglobin < 8.5 g/dl WBC < 3.5 x 109 Neutrophils < 1.5 x 109 Platelets < 100 x 109
Any investigational drug within a 60-day period or 5 half-lives
Organic neurologic disorder or somatic symptomatology
Organic gastrointestinal disorder or somatic symptomatology
Pregnant or breast-feeding women,
Women of childbearing potential not protected by effective contraceptive measures CYP2D6 inhibitors, are prohibited from 2 weeks prior to the study drug administration or > 5 half-lives, whichever is greater and during any phase of the study
Potent CYP3A4 inhibitors, are prohibited from 2 weeks prior to the study drug administration or > 5 half-lives, whichever is greater and during any phase of the study
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change in mean C-reactive protein (CRP) level at endpoint (Visit 8) as compared to baseline |
|
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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 | Yes |
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 | 26 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 26 |