A randomised, double-blind trial to demonstrate bioequivalence of GP2013 and reference rituximab combined with methotrexate in patients with active rheumatoid arthritis

Autor: Morton Scheinberg, Stanley Cohen, Tamas Shisha, Liyi Cen, Andra Balanescu, Josef S Smolen, Peijuan Zhu, Juan J. Gomez-Reino, Hans-Peter Tony, Alan Kivitz
Rok vydání: 2017
Předmět:
Male
DMARDs (biologic)
Gastroenterology
Arthritis
Rheumatoid
0302 clinical medicine
Clinical endpoint
Immunology and Allergy
Medicine
Immunogenicity
Middle Aged
Treatment Outcome
Antirheumatic Agents
Area Under Curve
030220 oncology & carcinogenesis
Rheumatoid arthritis
Vitamin B Complex
Drug Therapy
Combination
Female
Rituximab
medicine.drug
Adult
medicine.medical_specialty
Adolescent
Immunology
Bioequivalence
General Biochemistry
Genetics and Molecular Biology
Young Adult
03 medical and health sciences
Folic Acid
Double-Blind Method
Rheumatology
Pharmacokinetics
Internal medicine
Humans
Biosimilar Pharmaceuticals
Aged
030203 arthritis & rheumatology
B cells
business.industry
Clinical and Epidemiological Research
medicine.disease
Surgery
Methotrexate
Therapeutic Equivalency
Pharmacodynamics
business
Zdroj: Annals of the Rheumatic Diseases
ISSN: 1468-2060
0003-4967
Popis: ObjectivesThe aim of this report is to demonstrate pharmacokinetic (PK) and pharmacodynamic (PD) equivalence as well as similar efficacy, safety and immunogenicity between GP2013, a biosimilar rituximab, and innovator rituximab (RTX) in patients with rheumatoid arthritis (RA) with inadequate response or intolerance to tumour necrosis factor inhibitor (TNFi) treatment.MethodsIn this multinational, randomised, double-blind, parallel-group study, 312 patients with active disease despite prior TNFi therapy were randomised to receive GP2013 or either the EU (RTX-EU) or the US (RTX-US) reference product, along with methotrexate (MTX) and folic acid. The primary endpoint was the area under the serum concentration–time curve from study drug infusion to infinity (AUC0-inf). Additional PK and PD parameters, along with efficacy, immunogenicity and safety outcomes were also assessed up to week 24.ResultsThe 90% CI of the geometric mean ratio of the AUCs were within the bioequivalence limits of 80% to 125% for all three comparisons; GP2013 versus RTX-EU: 1.106 (90% CI 1.010 to 1.210); GP2013 versus RTX-US: 1.012 (90% CI 0.925 to 1.108); and RTX-EU versus RTX-US: 1.093 (90% CI 0.989 to 1.208). Three-way PD equivalence of B cell depletion was also demonstrated. Efficacy, safety and immunogenicity profiles were similar between GP2013 and RTX.ConclusionsThree-way PK/PD equivalence of GP2013, RTX-EU and RTX-US was demonstrated. Efficacy, safety and immunogenicity profiles were similar between GP2013 and RTX.Trial registration numberNCT01274182; Results.
Databáze: OpenAIRE
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