This is a multicentre, randomised, double-blind, parallel group study to compare the pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, safety, tolerability and efficacy of JHL1101 versus MabThera in subjects with moderate to severe RA who have previously failed at least 1 tumour necrosis factor alpha (TNF) inhibitor (i.e., intolerance or documented active disease despite at least 12 weeks treatment according to the TNF inhibitor-approved treatment and dosage), and are on concomitant treatment with MTX.
This study will take place across approximately 31 centres across 12 countries and will randomise approximately 150 subjects as outpatients. The primary objective is to investigate and compare the pharmacokinetic profiles of JHL1101 and MabThera (rituximab). The secondary objectives are to investigate the safety, tolerability, and immunogenicity of JHL1101 versus MabThera, to investigate the pharmacodynamics profile of JHL1101 versus MabThera, and investigate the efficacy of JHL1101 versus MabThera.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
153
1000 mg containing 10 mg/mL rituximab to be diluted to a concentration of 1 to 4 mg/mL in 0.9% normal saline or 5% D-glucose for administration
1000 mg containing 10 mg/mL rituximab to be diluted to a concentration of 1 to 4 mg/mL in 0.9% normal saline or 5% D-glucose for administration
Area under plasma concentration versus time curve (AUC)
Time frame: Day 0 through Week 52
Trough Concentration
Time frame: Day 15
Maximum Concentration (Cmax)
Time frame: Day 15
AUC
Time frame: Up to Week 12
Time to maximum plasma concentration
Time frame: Day 0 through Week 52
Cmax
Time frame: Day 0 through Week 52
Total body clearance
Time frame: Day 0 through Week 52
Volume of distribution
Time frame: Day 0 through Week 52
Terminal half life
Time frame: Day 0 through Week 52
Area under plasma concentration versus time curve
Time frame: Week 2 to Week 24
Incidence of treatment-related adverse events (safety)
Time frame: Until End-of-Study follow-up at Week 52
Immunogenicity
Human anti-chimeric antibody analysis
Time frame: Baseline, Weeks 12, 16, 24, and 52
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JHL Biotech Investigational Site
Banja Luka, Bosnia and Herzegovina
JHL Biotech Investigational Site
Bijeljina, Bosnia and Herzegovina
JHL Biotech Investigational Site
Plovdiv, Bulgaria
JHL Biotech Investigational Site
Sofia, Bulgaria
JHL Biotech Investigational Site
Sofia, Bulgaria
JHL Biotech Investigational Site
Prague, Czechia
JHL Biotech Investigational Site
Bad Doberan, Germany
JHL Biotech Investigational Site
Hildesheim, Germany
JHL Biotech Investigational Site
Magdeburg, Germany
JHL Biotech Investigational Site
Rendsburg, Germany
...and 22 more locations
Area under the depletion-time curve of CD19+ B-cell
Time frame: Day 0 to Day 15, Day 0 to Week 12, Day 0 to Week 24, and Day 0 to Week 52 (end of study)
Change from Baseline in CD4+ T-cell counts
Time frame: Day 0 through Week 52
American College of Rheumatology (ACR) criteria 20, 50, 70 response rate
Time frame: Weeks 4, 8, 12, 16, 24 and 52 and over time from Baseline to Week 52
Swollen and tender joint count
Time frame: From Baseline to Week 52
Subject's assessment of arthritis pain
2010 ACR/European League Against Rheumatism (EULAR) Classification Criteria for RA
Time frame: From Baseline to Week 52