Clinical trial NCT01895309: A Study Comparing SB4 to Enbrel® 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 SB4 Compared to Enbrel® 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
Etanercept
Biosimilar
Lead sponsor: Samsung Bioepis Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2013-07-10
Enrollment: 596
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 SB4 compared to Enbrel in subjects with moderate to severe Rheumatoid Arthritis (RA) despite Methotrexate (MTX) therapy. In some countries, after 52 weeks of treatment with either SB4 or Enbrel, subjects will be enrolled into an open label extension period. Subjects will receive SB4 for an additional 48 weeks.


Eligibility criteria: Inclusion Criteria:

* Diagnosed as having RA according to the revised 1987 ACR criteria for at least 6 months but not exceeding 15 years prior to Screening
* 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 2 months after the last dose of investigational product

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 Enbrel or SB4
* 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.

Primary outcomes:
measure: American College of Rheumatology 20% Response Criteria (ACR20)
timeFrame: Week 24
Secondary outcomes:
measure: ACR20
timeFrame: Week 52
measure: American College of Rheumatology 50% Response Criteria (ACR50)
timeFrame: Week 24, Week 52
Other outcomes:
Locations:
city: Kielce
country: Poland
facility: Investigational Site
city: Southampton
country: United Kingdom
facility: Investigational Site
state: Hampshire
Study officials:
affiliation: Charles University, Czech Republic
name: Jiri Vencovsky, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Emery P, Suh CH, Weinblatt ME, Smolen JS, Keystone EC, Genovese M, Vencovsky J, Kay J, Hong E, Baek Y, Ghil J. Impact of immunogenicity on efficacy and tolerability of tumour necrosis factor inhibitors: pooled analysis of biosimilar studies in rheumatoid arthritis. Scand J Rheumatol. 2020 Sep;49(5):361-370. doi: 10.1080/03009742.2020.1732458. Epub 2020 May 29.
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: Emery P, Vencovsky J, Sylwestrzak A, Leszczynski P, Porawska W, Baranauskaite A, Tseluyko V, Zhdan VM, Stasiuk B, Milasiene R, Barrera Rodriguez AA, Cheong SY, Ghil J. 52-week results of the phase 3 randomized study comparing SB4 with reference etanercept in patients with active rheumatoid arthritis. Rheumatology (Oxford). 2017 Dec 1;56(12):2093-2101. doi: 10.1093/rheumatology/kex269.
citation: Emery P, Vencovsky J, Sylwestrzak A, Leszczynski P, Porawska W, Stasiuk B, Hilt J, Mosterova Z, Cheong SY, Ghil J. Long-term efficacy and safety in patients with rheumatoid arthritis continuing on SB4 or switching from reference etanercept to SB4. Ann Rheum Dis. 2017 Nov 13;76(12):1986-1991. doi: 10.1136/annrheumdis-2017-211591.
citation: Emery P, Vencovsky J, Sylwestrzak A, Leszczynski P, Porawska W, Baranauskaite A, Tseluyko V, Zhdan VM, Stasiuk B, Milasiene R, Barrera Rodriguez AA, Cheong SY, Ghil J. A phase III randomised, double-blind, parallel-group study comparing SB4 with etanercept reference product in patients with active rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis. 2017 Jan;76(1):51-57. doi: 10.1136/annrheumdis-2015-207588. Epub 2015 Jul 6.