{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T11:40:31Z","timestamp":1786534831585,"version":"build-2736575974"},"reference-count":36,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibodies"],"abstract":"<jats:p>GNR-068 is a proposed biosimilar to the ustekinumab reference product (RP), which works through the antagonism of interleukin 12 and interleukin 23. Ustekinumab RP is used for the treatment of chronic inflammatory conditions, including certain forms of plaque psoriasis, psoriatic arthritis, Crohn\u2019s disease, and ulcerative colitis. Objectives: The purpose of the study is to study the safety, pharmacokinetics, and immunogenicity of the ustekinumab biosimilar GNR-068 and the reference drug Stelara\u00ae after a single subcutaneous administration in healthy male volunteers. Methods: This was an open-label, randomized, comparative, parallel-group clinical trial of the safety, pharmacokinetics (PK), and immunogenicity of GNR-068 (JSC GENERIUM) and Stelara\u00ae (Manufacturer: Silag AG, Switzerland; RU Holder: JOHNSON &amp; JOHNSON) after a single subcutaneous administration of 45 mg in healthy volunteers. During the trial, 146 volunteers were screened, and 122 were randomized. Results: The results showed that PK similarity was established based on 90% confidence intervals (CIs) for the ratios of geometric means of the primary endpoints of area under the concentration-time curve from time 0 extrapolated to infinity (AUC0\u2013\u221e) and maximum observed serum concentration (Cmax) being contained within the pre-specified margin of 80.00\u2013125.00%. The incidence of total ADA was lower in the GNR-068 group compared with the reference product group. Adverse events were similar between treatment groups and consistent with the safety profile of the ustekinumab RP. Conclusions: These results indicate that GNR-068 and the ustekinumab RP share similar PK and safety profiles.<\/jats:p>","DOI":"10.3390\/antib15040077","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T11:02:11Z","timestamp":1786532531000},"page":"77","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Open-Label, Comparative, Parallel Clinical Trial of the Safety, Pharmacokinetics and Immunogenicity of the Ustekinumab Biosimilar GNR-068 and the Originally Developed Ustekinumab as a Reference Drug After a Single Subcutaneous Administration in Healthy Male Volunteers"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9058-1106","authenticated-orcid":false,"given":"Ivan","family":"Lyagoskin","sequence":"first","affiliation":[{"name":"JSC \u201cGENERIUM\u201d, 14, Vladimirskaya Street, Volginskiy 601125, Vladimir Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Agafonova","sequence":"additional","affiliation":[{"name":"JSC \u201cGENERIUM\u201d, 14, Vladimirskaya Street, Volginskiy 601125, Vladimir Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Shevchenko","sequence":"additional","affiliation":[{"name":"JSC \u201cGENERIUM\u201d, 14, Vladimirskaya Street, Volginskiy 601125, Vladimir Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Akhtyamova-Givirovskaya","sequence":"additional","affiliation":[{"name":"JSC \u201cGENERIUM\u201d, 14, Vladimirskaya Street, Volginskiy 601125, Vladimir Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oksana","family":"Markova","sequence":"additional","affiliation":[{"name":"JSC \u201cGENERIUM\u201d, 14, Vladimirskaya Street, Volginskiy 601125, Vladimir Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Pantyushenko","sequence":"additional","affiliation":[{"name":"JSC \u201cGENERIUM\u201d, 14, Vladimirskaya Street, Volginskiy 601125, Vladimir Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6532-7835","authenticated-orcid":false,"given":"Rakhim","family":"Shukurov","sequence":"additional","affiliation":[{"name":"JSC \u201cGENERIUM\u201d, 14, Vladimirskaya Street, Volginskiy 601125, Vladimir Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1314-894X","authenticated-orcid":false,"given":"Ravil","family":"Khamitov","sequence":"additional","affiliation":[{"name":"JSC \u201cGENERIUM\u201d, 14, Vladimirskaya Street, Volginskiy 601125, Vladimir Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a015354","DOI":"10.1101\/cshperspect.a015354","article-title":"Psoriasis","volume":"4","author":"Villanova","year":"2014","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jaut.2015.07.008","article-title":"The Immunogenetics of Psoriasis: A Comprehensive Review","volume":"64","author":"Harden","year":"2015","journal-title":"J. Autoimmun."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Rendon, A., and Sch\u00e4kel, K. (2019). Psoriasis Pathogenesis and Treatment. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061475"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/j.1346-8138.2011.01483.x","article-title":"Antimicrobial peptides in the pathogenesis of psoriasis","volume":"39","author":"Morizane","year":"2012","journal-title":"J. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Santini, S.M., Lapenta, C., Donati, S., Spadaro, F., Belardelli, F., and Ferrantini, M. (2011). Interferon-\u03b1-Conditioned Human Monocytes Combine a Th1-Orienting Attitude with the Induction of Autologous Th17 Responses: Role of IL-23 and IL-12. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017364"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1084\/jem.20101102","article-title":"Plasmacytoid dendritic cells sense skin injury and promote wound healing through type I interferons","volume":"207","author":"Gregorio","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1172\/JCI117308","article-title":"Characterization of dermal dendritic cells in psoriasis. Autostimulation of T lymphocytes and induction of Th1 type cytokines","volume":"94","author":"Nestle","year":"1994","journal-title":"J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1136\/ard.2009.123919","article-title":"Treating rheumatoid arthritis to target: Recommendations of an international task force","volume":"69","author":"Smolen","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1053\/j.gastro.2020.12.031","article-title":"STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD","volume":"160","author":"Turner","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_10","unstructured":"Russian Society of Dermatovenerologists and Cosmetologists (2020, October 03). Psoriasis. Clinical Guidelines. [Electronic Resource]\/\/medi.ru. Available online: https:\/\/medi.ru\/klinicheskie-rekomendatsii\/psoriaz_14212\/."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1001\/archderm.141.12.1537","article-title":"Prevalence and treatment of psoriasis in the United Kingdom: A population-based trial","volume":"141","author":"Gelfand","year":"2005","journal-title":"Arch. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.jaad.2013.11.013","article-title":"Psoriasis prevalence among adults in the United States","volume":"70","author":"Rachakonda","year":"2014","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.jaad.2008.09.022","article-title":"The prevalence of previously diagnosed and undiagnosed psoriasis in US adults: Results from NHANES 2003\u20132004","volume":"60","author":"Kurd","year":"2009","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/jid.2012.339","article-title":"Global Epidemiology of Psoriasis: A Systematic Review of Incidence and Prevalence","volume":"133","author":"Parisi","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_15","first-page":"626","article-title":"Pathogenesis and therapy of psoriasis and psoriatic arthritis","volume":"18","author":"Matushevskaya","year":"2019","journal-title":"Clin. Dermatol. Venereol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1111\/bjd.13343","article-title":"Comparison of long-term drug survival and safety of biological agents in patients with psoriasis vulgaris","volume":"172","author":"Gniadecki","year":"2015","journal-title":"Br. J. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1111\/bjd.13087","article-title":"\u201cHappy\u201d drug survival of adalimumab, etanercept and ustekinumab in psoriasis in daily practice care: Results from the BioCAPTURE network","volume":"171","author":"Zweegers","year":"2014","journal-title":"Br. J. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2632","DOI":"10.1038\/jid.2015.208","article-title":"Differential Drug Survival of Biologic Therapies for the Treatment of Psoriasis: A Prospective Observational Cohort Trial from the British Association of Dermatologists Biological Interventions Register (BADBIR)","volume":"135","author":"Warren","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s40259-025-00727-z","article-title":"Beyond Cost: Observations on Clinical and Patient Benefits of Biosimilars in Real-World Settings","volume":"39","author":"Kvien","year":"2025","journal-title":"BioDrugs"},{"key":"ref_20","unstructured":"Mironov, A.N. (2014). Rukovodstvo po Ekspertize Iekarstvennykh Sredstv. Tom I [Guidance on the Examination of Medicines. Vol. I], Grif i K. (In Russian)."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/s40261-013-0072-2","article-title":"Comparison of the pharmacokinetics of subcutaneous ustekinumab between Chinese and non-Chinese healthy male subjects across two Phase 1 studies","volume":"33","author":"Zhu","year":"2013","journal-title":"Clin. Drug Investig."},{"key":"ref_22","unstructured":"Center for Biologics Evaluation and Research, and FDA (2019). Immunogenicity Testing of Therapeutic Protein Products\u2013Developing and Validating Assays for Anti-Drug Antibody Detection, Guidance for Industry."},{"key":"ref_23","unstructured":"European Medicines Agency (EMA) (2017). Guideline on Immunogenicity Assessment of Therapeutic Proteins, EMEA\/CHMP\/BMWP\/14327\/2006 Rev 1."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1177\/0091270008329556","article-title":"Population pharmacokinetic modeling of ustekinumab, a human monoclonal antibody targeting IL-12\/23p40, in patients with moderate to severe plaque psoriasis","volume":"49","author":"Zhu","year":"2009","journal-title":"J. Clin. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"830","DOI":"10.5414\/CPP48830","article-title":"Population pharmacokinetics of ustekinumab in patients with active psoriatic arthritis","volume":"48","author":"Zhu","year":"2010","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"493","DOI":"10.2165\/11531280-000000000-00000","article-title":"Clinical pharmacokinetics of therapeutic monoclonal antibodies","volume":"49","author":"Keizer","year":"2010","journal-title":"Clin. Pharmacokinet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s40262-012-0027-4","article-title":"Pharmacokinetics, pharmacodynamics and physiologically-based pharmacokinetic modelling of monoclonal antibodies","volume":"52","author":"Dostalek","year":"2013","journal-title":"Clin. Pharmacokinet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"407","DOI":"10.3390\/biologics4040025","article-title":"Ustekinumab Biosimilars","volume":"4","author":"Puig","year":"2024","journal-title":"Biologics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1002\/cpdd.1301","article-title":"Pharmacokinetic Similarity of ABP 654, an Ustekinumab Biosimilar Candidate: Results from a Randomized, Double-blind Trial in Healthy Subjects","volume":"12","author":"Chow","year":"2023","journal-title":"Clin. Pharmacol. Drug Dev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.jaad.2024.04.045","article-title":"A randomized, double-blind, phase III trial assessing clinical similarity of SB17 (proposed ustekinumab biosimilar) to reference ustekinumab in subjects with moderate-to-severe plaque psoriasis","volume":"91","author":"Feldman","year":"2024","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s40259-023-00630-5","article-title":"Efficacy and Safety of Candidate Biosimilar CT-P43 Versus Originator Ustekinumab in Moderate to Severe Plaque Psoriasis: 28-Week Results of a Randomised, Active-Controlled, Double-Blind, Phase III Trial","volume":"38","author":"Papp","year":"2024","journal-title":"BioDrugs"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/s40259-018-0319-9","article-title":"Recombinant Antibody Production in CHO and NS0 Cells: Differences and Similarities","volume":"32","author":"Dhara","year":"2018","journal-title":"BioDrugs"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1038\/nbt.1651","article-title":"Implications of the presence of N-glycolylneuraminic acid in recombinant therapeutic glycoproteins","volume":"28","author":"Ghaderi","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1038\/nbt1110-1153","article-title":"Chinese hamster ovary cells can produce galactose-\u03b1-1,3-galactose antigens on proteins","volume":"28","author":"Bosques","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.3109\/07388551.2015.1084266","article-title":"Human cell lines for biopharmaceutical manufacturing: History, status, and future perspectives","volume":"36","author":"Dumont","year":"2016","journal-title":"Crit. Rev. Biotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1080\/14712598.2023.2235263","article-title":"Randomized, double-blind, multicenter trial to evaluate efficacy, safety, tolerability, and immunogenicity between AVT04 and the reference product ustekinumab in patients with moderate-to-severe chronic plaque psoriasis","volume":"23","author":"Feldman","year":"2023","journal-title":"Expert. Opin. Biol. Ther."}],"container-title":["Antibodies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4468\/15\/4\/77\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T11:16:50Z","timestamp":1786533410000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4468\/15\/4\/77"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,12]]},"references-count":36,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["antib15040077"],"URL":"https:\/\/doi.org\/10.3390\/antib15040077","relation":{},"ISSN":["2073-4468"],"issn-type":[{"value":"2073-4468","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,12]]}}}