A Study Comparing SB2 to Remicade® in Subjects With Moderate to Severe Rheumatoid Arthritis Despite Methotrexate Therapy

• ClinicalTrials.gov Identifier: NCT01936181
• Recruitment Status: Completed
• First Posted: September 5, 2013
• Results First Posted: August 29, 2016
• Last Update Posted: September 14, 2017
• Sponsor: Samsung Bioepis Co., Ltd.
• Information provided by (Responsible Party): Samsung Bioepis Co., Ltd.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Drug: Remicade (infliximab); Drug: SB2 (proposed biosimilar to infliximab)	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 584 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: August 2013
• Actual Primary Completion Date: September 2014
• Actual Study Completion Date: September 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: SB2 (proposed biosimilar to inflixmab); SB2 3 mg/kg at week 0, 2, 6 then every 8 weeks thereafter via intravenous infusion up to Week 70	Drug: SB2 (proposed biosimilar to infliximab)
Active Comparator: Remicade (infliximab); Remicade 3 mg/kg at week 0, 2, 6 then every 8 weeks thereafter via intravenous infusion up to Week 46	Drug: Remicade (infliximab)
Experimental: Remicade (infliximab), switch to SB2; SB2 3mg/kg at week 54, 62, 70	Drug: SB2 (proposed biosimilar to infliximab)
Active Comparator: Remicade (infliximab), continue as Remicade; Remicade 3mg/kg at week 54, 62, 70	Drug: Remicade (infliximab)

Outcome Measures

Primary Outcome Measures :

1. American College of Rheumatology 20% Response Criteria (ACR20) [ Time Frame: Week 30 ]

Secondary Outcome Measures :

1. ACR20 [ Time Frame: Week 54, Week 78 ]
2. American College of Rheumatology 50% Response Criteria (ACR50) [ Time Frame: Week 30, Week 54, Week 78 ]
3. Disease Activity Score Based on a 28 Joint Count (DAS28) [ Time Frame: Week 30, Week 54, Week 78 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Bulgaria

Investigational Site

Hristo Botev Str., Sliven, Bulgaria, 8800

Lithuania

Investigational Site

Santariskiu, Vilnius, Lithuania, 08661

Sponsors and Collaborators

Samsung Bioepis Co., Ltd.

Investigators

• Principal Investigator: Jung-Yoon Choe, M.D., Ph.D.; Daegu Catholic University Medical Center

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

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.

• Responsible Party: Samsung Bioepis Co., Ltd.
• ClinicalTrials.gov Identifier: NCT01936181
• Other Study ID Numbers: SB2-G31-RA
• First Posted: September 5, 2013
• Results First Posted: August 29, 2016
• Last Update Posted: September 14, 2017
• Last Verified: August 2017

Keywords provided by Samsung Bioepis Co., Ltd.:

Rheumatoid Arthritis; Infliximab; Biosimilar

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Infliximab; Dermatologic Agents; Gastrointestinal Agents; Antirheumatic Agents