E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderately to Severely Active Rheumatoid Arthritis |
|
E.1.1.1 | Medical condition in easily understood language |
Moderately to Severely Active Rheumatoid Arthritis |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
|
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 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 TNF-α inhibitor (TNFi) therapy. |
|
E.2.2 | Secondary objectives of the trial |
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
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 24 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.Treatment with oral, SC, or intramuscular (IM) MTX for at least 12 weeks prior to Screening at a dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance 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 7.Subjects must have a documented inadequate response to treatment (i.e., TNFi failure) with ≥1 licensed TNFi following at least 12 weeks of therapy with that agent. Inadequate response to treatment is classified as either: a.Primary failure: The absence of any documented clinically significant response; or b.Secondary failure: Documented initial response with subsequent loss of that response or partial response
|
|
E.4 | Principal exclusion criteria |
1.Diagnosis of any other inflammatory arthritis or systemic rheumatic disease •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 agents or investigational agents (e.g., CAMPATH, anti-CD4, anti-CD5, anti-CD3, and anti-CD19), with the exception of rituximab, which is allowed if it was discontinued at least 24 weeks prior to baseline (rituximab 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). 5. Prior use of bDMARDs within the following windows prior to baseline (bDMARDs 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 etanercept and anakinra b. 8 weeks for infliximab c. 10 weeks for adalimumab, certolizumab, and golimumab d. 12 weeks for abatacept 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 24hours, or activated charcoal at a dosage of 50 grams 4 times a day 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 11.Participation in any other investigational drug study within 30 days or 5 times the terminal half-life of the investigational drug, whichever is longer, prior to baseline Please refer to the Protocol for the full list of exclusion criteria |
|
E.5 End points |
E.5.1 | 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. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
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 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 12 Percentage of subjects with Clinical Disease Activity Index (CDAI) ≤ 2.8 (remission) and remaining on randomized treatment and in the study at Week 12 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
week 12 baseline to Week 12 |
|
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 | 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 | 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 | 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.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
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 | No |
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 |
Argentina |
Brazil |
Colombia |
Czech Republic |
Germany |
Hungary |
Korea, Republic of |
Mexico |
Poland |
United States |
|
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 | 3 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 9 |