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
Trade Name: RoActemra 162 mg
Product Code: RO487-7533/F10-04
Pharmaceutical Form: Solution for injection
INN or Proposed INN: tocilizumab
CAS Number: 375823-41-9
Other descriptive name: TOCILIZUMAB
Co
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age >= 18 years - RA of >= 6 months duration diagnosed according to American College of Rheumatology (ACR)/European League against Rheumatology (EULAR) criteria Track TCZ-experienced patients: - Have received tocilizumab (TCZ) either subcutaneous (SC, 162 milligrams [mg] once a week [QW]) or intravenous (IV, 8 mg/kilogram [kg] every 4 weeks [Q4W]) not exceeding 800 mg/dose for the treatment of RA for at least 24 weeks prior to randomization - Have received 5 15 mg/day of prednisone (or glucocorticoids (GCs) equivalent) for the treatment of RA for at least 20 weeks prior to screening - Currently receiving 5 mg/day of oral prednisone (or GC equivalent) at the screening visit - Have DAS28 ESR score 3.2) - Are considered by the investigator as inadequate responders to conventional synthetic disease-modifying antirheumatic drug (csDMARDs) or biologic disease-modifying antirheumatic drug (bDMARDs). Are TCZ treatment naive or last TCZ was >12 months prior to screening and TCZ was not discontinued due to lack of efficacy, side effects, or any other safety reasons - Are receiving 5-15 mg/day prednisone (or GC equivalent) for the treatment of RA 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 170 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 56
Exclusion criteria
Exclusion criteria: - Major surgery (including joint surgery) within 8 weeks prior to screening, or planned major surgery during the study and up to 6 months after randomization - Pregnant women or nursing (breastfeeding) mothers - In females of childbearing potential, a positive serum pregnancy test at screening - Females of childbearing potential unwilling or unable to use reliable means of contraception during study treatment and for a minimum of 3 months after the last dose of TCZ - Body weight of >=150 kg - Lack of peripheral venous access - RA of functional class IV, as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis - 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, or Felty syndrome). Secondary Sjögren syndrome with RA may be allowed per the discretion of the investigator - Diagnosed with juvenile idiopathic arthritis or juvenile RA and/or RA before the age of 16 years - Prior or current inflammatory joint disease other than RA (e.g., gout, Lyme disease, sero-negative spondyloarthropathy, including reactive arthritis, psoriatic arthritis, arthropathy of inflammatory bowel disease), or prior or current joint infections - Previous history of primary or secondary adrenal insufficiency - Treatment with any investigational agent (tocilizumab excepted) within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening. Treatment with csDMARDs, other DMARDS, and/or biologics for RA which is permanently discontinued within 5 half-lives prior to randomization - Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies - Treatment with IV gamma globulin, plasmapheresis or Prosorba column within 6 months of screening - Intraarticular (IA) or parenteral GCs for the treatment of RA within 6 weeks prior to randomisation (within 12 weeks prior ro randomization for intra-articular triamcinolone) - Previous treatment with GCs for conditions other than RA, at any dose and in any formulation used continuously for > 1 week, during the last 1 year prior to screening. Current treatment with topical GC exceeding 20% of body surface area - Immunization with a live/attenuated vaccine within 30 days prior to screening - Any previous treatment with alkylating agents such as chlorambucil or with total lymphoid irradiation - Inadequate haematological, renal and liver functions - Positive hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody (HCV Ab) - History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies - Evidence of current serious uncontrolled cardiovascular (including uncontrolled hyperlipidaemia), nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus) or gastrointestinal (GI) disease - Current liver disease as determined by the investigator - History of diverticulitis, peptic ulcer disease, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower GI disease such as Crohn's disease, ulcerative colitis, or other symptomatic lower GI conditions that might predispose to perforations - Known active current or history of recurrent bacterial, viral, fungal, mycobacte
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: -To compare the proportion of patients who continue vs. taper prednisone with LDA at Week 24, who haven't suffered a disease flare and showed no confirmed adrenal insufficiency requiring replacement therapy -To compare between patients who continue vs. taper prednisone:(1)changes in CDAI and SDAI (2)the proportion of patients with >=1 RA flare; time to first RA flare; number of RA flares; >=1 administration of RA flare rescue medication; time to first administration, and number of administrations of RA flare rescue medication(3)cumulative prednisone exposure(4)the proportion of patients who maintain LDA and who maintain the baseline disease activity level(5)proportion of patients who permanently discontinue study treatment due to insufficient RA flare control,(6)changes in the ACR core set, (7)identify predictors of successful prednisone dosetapering (8) changes in patient-reported outcomes -To evaluate the safety and tolerability of TCZ and proposed prednisonetapering scheme;Main Objective: To compare the impact on disease activity of continued vs. tapered prednisone in RA patients with stable low disease activity (LDA [Disease Activity Score in 28 joints (DAS28) erythrocyte sedimentation rate (ESR) score <= 3.2]) or remission (DAS28 ESR score <= 2.6).;Primary end point(s): Change in DAS28 ESR between randomization and Week 24 post-randomization;Timepoint(s) of evaluation of this end point: Randomization and Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 The proportion of patients with LDA (DAS28 ESR score =1 RA flare, the time to first RA flare and the number of RA flares 4 The proportion of patients with >=1 dministration of RA flare rescue medication, the time to first administration, and the number of administrations of RA flare rescue medication 5 Cumulative prednisone exposure (dose) between randomization and Week 24 post-randomization 6 The proportion of patients who maintain LDA (DAS28 ESR score <=3.2) and the proportion of patients who maintain the baseline disease activity level at Week 24 post-randomization 7 The proportion of patients who permanently discontinue study treatment due to insufficient RA flare control 8 Changes in the ACR core set from randomization to postrandomization Week 24, including: swollen and tender joint counts; patient's assessment of pain and global status; physician's assessment of global status; Health assessment questionnaire–Disability index (HAQ-DI); and acute phase reactants (high sensitivity C-reactive protein [hsCRP] and ESR) 9 Incidence of adverse events (AEs) including non-serious and serious AEs, and AEs of special interest 10 Changes in vital signs, physical findings, and clinical laboratory results during and following TCZ administration 11 Assessment of immunogenicity (anti-TCZ antibodies) 12 Proportion of patients with confirmed adrenal insufficiency that required replacement therapy 13 Rheumatoid arthritis impact of disease (RAID) score 14 Work productivity and activity impairment questionnaire: Rheumatoid Arthritis (WPAI: RA) 15 Health assessment questionnaire–Disability index (HAQ-DI) score;Timepoint(s) of evaluation of this end point: Week 24 2: From Randomization up to Week 24 3-4: Up to Week 24 5: From Randomization up to Week 24 6: Week 24 7: Up to Week 24 8: From Randomization up to Week 24 9-10: Up to Week 28 11: Up to Week 24 (performed on event driven bas | — |
Countries
Egypt, France, Germany, Italy, Lebanon, Russian Federation, Serbia, Switzerland, Turkey
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd.
Outcome results
None listed