Rheumatoid Arthritis MedDRA version: 8.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis
Conditions
Interventions
Product Name: SMP-114
Product Code: SMP-114
Pharmaceutical Form: Tablet
INN or Proposed INN: rimacalib
CAS Number: 215174-50-8
Current Sponsor code: SMP-114
Concentration unit: mg milligram(s)
Concent
Sponsors
Dainippon Sumitomo Pharma Europe Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Is at least 18 years of age 2. Has given his/her written informed consent to participate in the study 3. Has had a diagnosis of RA (based on the ACR criteria) for at least 6 months 4. Has RA disease classified as ACR functional class I, II or III 5. Has active RA disease as defined by: · >= 6 swollen joints (using 28-joint counts) · >= 6 tender joints (using 28-joint counts) · and at least one of the following: ESR >= 28 mm/hr, CRP >= 10 mg/L 6. Has been receiving methotrexate at weekly doses of 10 to 25 mg for >= 12 weeks prior to study drug administration. Methotrexate use must have been in accordance with its product labelling (SmPC) 7. The dose of methotrexate has been stable for at least 8 weeks prior to randomisation and is anticipated to remain constant during the study period Individuals previously treated with methotrexate can be enrolled provided they have not had clinically significant toxic effects or lack of response, at the discretion of the Investigator 8. Has been on a stable dose of folate (or leucovorin) for at least 4 weeks prior to randomisation and the dose of folate (or leucovorin) is anticipated to remain constant during the study period. If not currently prescribed, is willing to start receiving folate (or leucovorin) at screening 9. If on a stable dose of NSAID and/or COX-2 inhibitor, the doses of these concomitant medications must have been stable for at least 2 weeks prior to randomisation. The dose(s) must be anticipated to remain constant during the study 10. If taking oral corticosteroid at a permissible dose (eg =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients are not eligible for this study if they fulfil any of the following criteria: 1. Is a pregnant or lactating woman 2. Is a woman of childbearing potential not prepared to use a reliable form of contraception during the study. An effective form of birth control includes contraception such as a barrier method (condom with spermicidal) in conjunction with hormone-based contraceptives or certain intra-uterine devices, or alternatively abstinence or surgical methods. 3. Has previously discontinued DMARD therapy due to hepatic intolerance. 4. Has received any DMARD in addition to methotrexate during the 4 weeks prior to randomisation. All DMARD’s, with the exception of methotrexate must have been discontinued at least 4 weeks before randomisation, unless requiring a longer washout period 5. Is receiving more than 2 DMARDs in addition to methotrexate at the time of screening 6. Is receiving or has received Gold, leflunomide or biological agents including TNF/IL-1 inhibitors within the 8 weeks prior to randomisation. Leflunomide washout can be completed with colestyramine according to the manufacturer’s instructions 7. Has previously failed >= 2 DMARDS. Failure is defined as removal of the administration of a DMARD due to inadequate efficacy response rather than discontinuation of DMARD therapy due to intolerance. A patient who has been removed from biological DMARD therapy due to non-clinical reasons can enter the study 8. Will require any treatments contraindicated for methotrexate 9. Is currently taking flurbiprofen 10. Has used intra-articular, intra-muscular or intravenous corticosteroids within 8 weeks prior to randomisation 11. Requires ongoing treatment with warfarin, cimetidine, phenytoin, trimethoprim, quinolones or dextropropoxyphenes (including co-proxamol) during the study 12. Persistent or severe infections within 3 months before randomisation 13. Has any known or suspected hypersensitivity to leflunomide or any other isoxazole compounds or any ingredients contained within the study drug (mannitol, corn starch, croscarmellose sodium, hypromellose, magnesium stearate, titanium dioxide, macrogol, carnuba wax, gelatine, sodium metabisulphite) 14. Has pre-existing hepatic disease, or co morbid illness predisposing to hepatic complications and/or the following laboratory parameters at screening: · AST >= 2 X ULN on two consecutive occasions and/or · ALT >= 2 X ULN on two consecutive occasions 15. Has any pre-existing renal disease, or co morbid illness predisposing to renal complications, or the following laboratory parameter at screening: · Serum creatinine >= 1.5 mg/dL 16. Has current blood dyscrasias such as bone marrow hypoplasia, leukopenia, thrombocytopenia or significant anaemia including Haemoglobin <10 g/dL at screening 17. Has any other significant systemic, cardiac, neurological, psychiatric or other illness that in the Investigator’s opinion would preclude the patient from participating in the study 18. Has a known or had a known malignancy of any type in the previous 5 years with the exception of basal or squamous cell carcinoma of the skin if no recurrence during the 1 year prior to screening 19. Has a current history of known or in the opinion of the Principal Investigator, suspected drug and/or alcohol abuse 20. Has participated in another clinical trial with an investigational agent (including named patient or compassionate use protocols) 8 weeks prior to randomisation (or longer if 8
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of SMP-114 (120 mg and 240 mg) versus placebo in terms of the percentage of patients meeting the American College of Rheumatology criteria for 20% improvement in Rheumatoid arthritis (ACR20) at Week 24.;Secondary Objective: To compare the efficacy of SMP-114 (120 mg and 240 mg) versus placebo in terms of the % of patients who: - Meet the ACR criteria for 50% and 70% improvement in RA at Week 24 - Obtain ‘good’ or ‘moderate’ or ‘none’ response according to the EULAR criteria using a calculation of DAS at Week 24 To compare the efficacy of SMP-114 (120 mg and 240 mg) versus placebo with respect to: - The mean change and the mean % change from baseline in core set variable results, the mean change from baseline in Quality of Life (short form - 36) measure and in DAS28 at Week 24 - The mean time to first response (time to ACR20, EULAR and DAS28 responses) - The actual change in radiological joint damage as assessed by x-ray: from Week 24 to Week 48 and from baseline at Week 24 and at Week 48 To assess safety and tolerability of each regimen during the study To describe the PK profile of SMP-114 and the metabolite flurbiprofen To explore the relationship of SMP-114 drug concentration with PD effect;Primary end point(s): A patient will be classified as a responder as per ACR20 if all of the following criteria are met after 24 weeks of treatment, when compared to baseline: >=20% improvement in tender joint count (TJC) AND >=20% improvement in swollen joint count (SJC) AND >=20% improvement in three of the five following ACR core set measures: 1. Patient assessment of pain (Visual Analogue Scale[VAS]) 2. Patient global assessment of disease activity (VAS) 3. Physician global assessment of disease activity (VAS) 4. Patient self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]) 5. Acute phase reactant C-reactive protein (CRP) or ESR | — |
Countries
Czech Republic, Germany, Hungary, United Kingdom
Outcome results
None listed