Clinical trial NCT02167139: A Study Comparing SB5 to Humira® 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, Tolerability, Pharmacokinetics and Immunogenicity of SB5 Compared to Humira® in Subjects With Moderate to Severe Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis, Adalimumab
Lead sponsor: Samsung Bioepis Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2014-06-18
Enrollment: 544
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 randomised, double-blind, parallel group, multicentre clinical study to evaluate the efficacy, safety, tolerability, pharmacokinetics and immunogenicity of SB5 compared to Humira® in subjects with moderate to severe RA despite MTX therapy.

Detailed description: Investigational product: SB5 40 mg (0.8 mL of 50 mg/mL) Indication studied: Rheumatoid arthritis

Eligibility criteria: Inclusion Criteria:

* Are male or female aged 18-75 years at the time of signing the informed consent form.
* Have been diagnosed as having RA according to the revised 1987 American College of Rheumatology (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:

  1. More than or equal to six swollen joints and more than or equal to six tender joints (from the 66/68 joint count system) at Screening and Randomisation.
  2. Either erythrocyte sedimentation rate (Westergren) ≥ 28 mm/h or serum C-reactive protein ≥ 10 mg/dL at Screening.
* Must have been treated with MTX for a total of at least 6 months prior to Randomisation and must have been on both: a stable route of administration (oral or parenteral) and stable dose of MTX (10-25 mg/week) for at least 4 weeks prior to Screening.
* Female subjects who are not pregnant or nursing at Screening and Randomisation and who are not planning to become pregnant from Screening until 5 months after the last dose of IP.

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 Humira or SB5.
* 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 (TB), have been recently exposed to a person with active TB, or are considered to have latent TB.
* 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 a history of chronic or recurrent infection.
* Have any of the following conditions:

  1. History of congestive heart failure (New York Heart Association Class III/IV).
  2. History of acute myocardial infarction or unstable angina within the previous 12 months prior to Screening.
  3. History of demyelinating disorders.
  4. History of any malignancy within the previous 5 years prior to Screening.
  5. History of lymphoproliferative disease including lymphoma.
  6. Any other disease or disorder which, in the opinion of the Investigator, will put the subject at risk if they are enrolled.
* Have physical incapacitation (ACR functional Class IV or wheelchair-/bed-bound).

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
measure: Disease Activity Score Based on a 28 Joint Count (DAS28)
timeFrame: Week 24, Week 52
Other outcomes:
Locations:
city: Kaunas
country: Lithuania
facility: Investigational Site
city: Katowice
country: Poland
facility: Investigational site
Study officials:
affiliation: Hospital of Lithuanian University of Health Sciences
name: Asta Baranauskaite, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Huizinga TWJ, Torii Y, Muniz R. Adalimumab Biosimilars in the Treatment of Rheumatoid Arthritis: A Systematic Review of the Evidence for Biosimilarity. Rheumatol Ther. 2021 Mar;8(1):41-61. doi: 10.1007/s40744-020-00259-8. Epub 2020 Dec 1.
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: Weinblatt ME, Baranauskaite A, Dokoupilova E, Zielinska A, Jaworski J, Racewicz A, Pileckyte M, Jedrychowicz-Rosiak K, Baek I, Ghil J. Switching From Reference Adalimumab to SB5 (Adalimumab Biosimilar) in Patients With Rheumatoid Arthritis: Fifty-Two-Week Phase III Randomized Study Results. Arthritis Rheumatol. 2018 Jun;70(6):832-840. doi: 10.1002/art.40444. Epub 2018 Apr 24.
citation: Weinblatt ME, Baranauskaite A, Niebrzydowski J, Dokoupilova E, Zielinska A, Jaworski J, Racewicz A, Pileckyte M, Jedrychowicz-Rosiak K, Cheong SY, Ghil J. Phase III Randomized Study of SB5, an Adalimumab Biosimilar, Versus Reference Adalimumab in Patients With Moderate-to-Severe Rheumatoid Arthritis. Arthritis Rheumatol. 2018 Jan;70(1):40-48. doi: 10.1002/art.40336. Epub 2017 Nov 21.