Moderately to Severely Active Rheumatoid Arthritis MedDRA version: 20.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Sponsors
R-Pharm International LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects =18 years of age 2. Subjects willing and able to sign informed consent 3. Subjects must have a diagnosis of adult-onset RA classified by ACR/EULAR 2010 revised classification criteria for RA for at least 12 weeks prior to Screening. If the subject was diagnosed according to ACR 1987 criteria previously, the Investigator may classify the subject per ACR 2010 retrospectively, using available source data. 4. Inadequate response to treatment with oral, SC, or intramuscular (IM) MTX (as defined by protocol) for at least 12 weeks prior to Screening at a dose of 15 to 25 mg/week (or =10 mg/week if intolerant to higher doses). The dose and means of administering MTX must have been stable for at least 6 weeks prior to Screening. 5. Subjects must be willing to take folic acid or equivalent throughout the study. 6. Subjects must have moderately to severely active RA disease as defined by all of the following: a. =6 tender joints (68-joint count) at Screening and baseline; and b. =6 swollen joints (66-joint count) at Screening and baseline; and c. CRP above ULN at Screening based on the central laboratory results Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 1345 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 230
Exclusion criteria
Exclusion criteria: 1. Diagnosis of any other inflammatory arthritis or systemic rheumatic disease (e.g., gout, psoriatic or reactive arthritis, Crohn’s disease, Lyme disease, juvenile idiopathic arthritis, or systemic lupus erythematosus). However, subjects may have secondary Sjogren’s syndrome or hypothyroidism 2. Subjects who are Steinbrocker class IV functional capacity (incapacitated, largely or wholly bed-ridden or confined to a wheelchair, with little or no self-care) 3.Prior exposure to any licensed or investigational compound directly or indirectly targeting IL 6 or IL 6R (including tofacitinib or other Janus kinases and spleen tyrosine kinase [SYK] inhibitors) 4.Prior treatment with cell depleting therapies, including anti CD20 or investigational agents (e.g., CAMPATH, anti CD4, anti CD5, anti CD3, and anti CD19) 5. Prior use of bDMARDs 6. Use of parenteral and/or intra-articular glucocorticoids within 4 weeks prior to baseline 7. Use of oral glucocorticoids greater than 10 mg/day prednisone (or equivalent) or change in dosage within 2 weeks prior to baseline 8. Prior documented history of no response to hydroxychloroquine and sulfasalazine 9. Prior use of cDMARDs (other than MTX) within the following windows prior to baseline (cDMARDs should not be discontinued to facilitate a subject’s participation in the study, but should instead have been previously discontinued as part of a subject’s medical management of RA): a. 4 weeks for sulfasalazine, azathioprine, cyclosporine, hydroxychloroquine, chloroquine, gold, penicillamine, minocycline, or doxycycline b. 12 weeks for leflunomide unless the subject has completed the following elimination procedure at least 4 weeks prior to baseline: Cholestyramine at a dosage of 8 grams 3 times daily for at least 24 hours, or activated charcoal at a dosage of 50 grams 4 times daily for at least 24 hours c. 24 weeks for cyclophosphamide 10. Vaccination with live vaccines in the 6 weeks prior to baseline or planned vaccination with live vaccines during the study Please refer to the Protocol for the full list of exclusion criteria
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: week 12;Main Objective: The primary objective of this study is to evaluate the efficacy of olokizumab (OKZ) 64 mg administered subcutaneously (SC) once every 2 weeks (q2w) or once every 4 weeks (q4w) relative to placebo in subjects with moderately to severely active rheumatoid arthritis (RA) inadequately controlled by methotrexate (MTX) therapy.; Secondary Objective: ? To evaluate the efficacy of OKZ relative to adalimumab in subjects with moderately to severely active RA inadequately controlled by MTX therapy (for EU submission). ? To evaluate the efficacy of OKZ over time ? To compare the physical function and quality of life of subjects receiving OKZ relative to placebo ? To assess exposure to OKZ ? To assess the safety and tolerability of OKZ ;Primary end point(s): The primary efficacy endpoint is the American College of Rheumatology 20% (ACR20) response at Week 12, where a responder is defined as any subject satisfying ACR20 criteria and remaining on randomized treatment and in the study at Week 12. This endpoint will serve to demonstrate that the efficacy of OKZ is superior to placebo. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): For EU submission: ACR20 response at Week 12, where a responder is defined as any subject satisfying ACR20 criteria and remaining on randomized treatment and in the study at Week 12. This endpoint will serve to demonstrate that the efficacy of OKZ is non-inferior to adalimumab, provided that superiority of adalimumab to placebo (assay sensitivity) is demonstrated concurrently based on the same endpoint ? Percentage of subjects achieving low disease activity, defined as Disease Activity Score 28-joint count (DAS28) C-reactive protein (CRP) <3.2, and remaining on randomized treatment and in the study at Week 12 ? For EU submission: Percentage of subjects achieving low disease activity, defined as DAS28 (CRP) <3.2, and remaining on randomized treatment and in the study at Week 12. This endpoint will serve to demonstrate that the efficacy of OKZ is non-inferior to adalimumab, provided that superiority of adalimumab to placebo (assay sensitivity) is demonstrated concurrently based on the same endpoint ? Improvement of physical ability from baseline to Week 12, as measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI) ? Percentage of subjects achieving an American College of Rheumatology 50% (ACR50) response and remaining on randomized treatment and in the study at Week 24 ? Percentage of subjects with Clinical Disease Activity Index (CDAI) =2.8 (remission) and remaining on randomized treatment and in the study at Week 24 ;Timepoint(s) of evaluation of this end point: week 12, week 24 | — |
Countries
Argentina, Brazil, Bulgaria, Colombia, Czech Republic, Estonia, Georgia, Germany, Hungary, Korea, Republic of, Latvia, Lithuania, Mexico, Poland, Romania, Russian Federation, Taiwan, United Kingdom, United States
Contacts
Public ContactMedical Department
R-Pharm International LLC
Outcome results
None listed