Clinical trial NCT01936181: A Study Comparing SB2 to Remicade® in Subjects With Moderate to Severe Rheumatoid Arthritis Despite Methotrexate Therapy
Official title: A Randomised, Double-blind, Parallel Group, Multicentre Clinical Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Immunogenicity of SB2 Compared to Remicade® in Subjects With Moderate to Severe Rheumatoid Arthritis Despite Methotrexate Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Infliximab
Biosimilar
Lead sponsor: Samsung Bioepis Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2013-09-05
Enrollment: 584
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind, parallel group, multicentre clinical study to evaluate the efficacy, safety, pharmacokinetics and immunogenicity of SB2 compared to Remicade in subjects with moderate to severe Rheumatoid Arthritis (RA) despite Methotrexate (MTX) therapy.


Eligibility criteria: Inclusion Criteria:

* Diagnosed as having RA according to the revised 1987 ACR criteria for at least 6 months
* Have moderate to severe active disease despite MTX therapy defined as having more than or equal to six swollen joints and more than or equal to six tender joints and either erythrocyte sedimentation rate (ESR, Westergren) ≥ 28 mm/h or serum C-reactive protein ≥ 1.0 mg/dL
* Must have been treated with MTX for at least 6 months prior to Randomisation and on a stable dose of MTX 10-25 mg/week given at least 4 weeks prior to Screening
* Female subjects who are not pregnant or nursing at Screening and who are not planning to become pregnant from Screening until 6 months after the last dose of investigational product

Inclusion Criteria for Transition-Extension Period:

* Have been enrolled and completed the scheduled Week 54 visit of the randomised, double-blind period of the SB2-G31-RA study
* In the opinion of the Investigator, subjects who may benefit from continuing IP treatment (either SB2 or Remicade), understand the implications of taking part in the study and willing to participate in the transition-extension period

Exclusion Criteria:

* Have been treated previously with any biological agents including any tumour necrosis factor inhibitor
* Have a known hypersensitivity to human immunoglobulin proteins or other components of Remicade or SB2
* Have a positive serological test for hepatitis B or hepatitis C or have a known history of infection with human immunodeficiency virus
* Have a current diagnosis of active tuberculosis
* Have had a serious infection or have been treated with intravenous antibiotics for an infection within 8 weeks or oral antibiotics within 2 weeks prior to Randomisation.
* Have any of the following conditions

  1. Other inflammatory or rheumatic diseases.
  2. History of any malignancy within the previous 5 years prior to Screening
  3. History of lymphoproliferative disease including lymphoma.
  4. History of congestive heart failure
  5. Physical incapacitation (ACR functional Class IV or wheelchair-/bed-bound).
  6. History of demyelinating disorders.

Exclusion Criteria for Transition-Extension Period:

* Have been withdrawn from the SB2-G31-RA study for any reason
* Have had any significant medical conditions, such as an occurrence of a serious AE (SAE) or intolerance of SB2 or Remicade during the randomised, double-blind period of the SB2-G31-RA study which may render the subject unsuitable to participate in the transition-extension period, at the discretion of the Investigator

Primary outcomes:
measure: American College of Rheumatology 20% Response Criteria (ACR20)
timeFrame: Week 30
Secondary outcomes:
measure: ACR20
timeFrame: Week 54, Week 78
measure: American College of Rheumatology 50% Response Criteria (ACR50)
timeFrame: Week 30, Week 54, Week 78
measure: Disease Activity Score Based on a 28 Joint Count (DAS28)
timeFrame: Week 30, Week 54, Week 78
Other outcomes:
Locations:
city: Hristo Botev Str.
country: Bulgaria
facility: Investigational Site
state: Sliven
city: Santariskiu
country: Lithuania
facility: Investigational Site
state: Vilnius
Study officials:
affiliation: Daegu Catholic University Medical Center
name: Jung-Yoon Choe, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Smolen JS, Choe JY, Weinblatt ME, Emery P, Keystone E, Genovese MC, Myung G, Hong E, Baek I, Ghil J. Pooled analysis of TNF inhibitor biosimilar studies comparing radiographic progression by disease activity states in rheumatoid arthritis. RMD Open. 2020 Jan;6(1):e001096. doi: 10.1136/rmdopen-2019-001096.
citation: Smolen JS, Choe JY, Prodanovic N, Niebrzydowski J, Staykov I, Dokoupilova E, Baranauskaite A, Yatsyshyn R, Mekic M, Porawska W, Ciferska H, Jedrychowicz-Rosiak K, Zielinska A, Lee Y, Rho YH. Safety, immunogenicity and efficacy after switching from reference infliximab to biosimilar SB2 compared with continuing reference infliximab and SB2 in patients with rheumatoid arthritis: results of a randomised, double-blind, phase III transition study. Ann Rheum Dis. 2018 Feb;77(2):234-240. doi: 10.1136/annrheumdis-2017-211741. Epub 2017 Oct 17.
citation: Smolen JS, Choe JY, Prodanovic N, Niebrzydowski J, Staykov I, Dokoupilova E, Baranauskaite A, Yatsyshyn R, Mekic M, Porawska W, Ciferska H, Jedrychowicz-Rosiak K, Zielinska A, Choi J, Rho YH. Comparing biosimilar SB2 with reference infliximab after 54 weeks of a double-blind trial: clinical, structural and safety results. Rheumatology (Oxford). 2017 Oct 1;56(10):1771-1779. doi: 10.1093/rheumatology/kex254.
citation: Choe JY, Prodanovic N, Niebrzydowski J, Staykov I, Dokoupilova E, Baranauskaite A, Yatsyshyn R, Mekic M, Porawska W, Ciferska H, Jedrychowicz-Rosiak K, Zielinska A, Choi J, Rho YH, Smolen JS. A randomised, double-blind, phase III study comparing SB2, an infliximab biosimilar, to the infliximab reference product Remicade in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis. 2017 Jan;76(1):58-64. doi: 10.1136/annrheumdis-2015-207764. Epub 2015 Aug 28.