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Clinical Trial
. 2024 Sep 7;26(1):157.
doi: 10.1186/s13075-024-03375-w.

A phase 3, randomized, double-blind, active-controlled clinical trial to compare BAT1806/BIIB800, a tocilizumab biosimilar, with tocilizumab reference product in participants with moderate-to-severe rheumatoid arthritis with inadequate response to methotrexate: treatment period 2 analysis (week 24 to week 48)

Xiaomei Leng  1 , Piotr Leszczyński  2 , Slawomir Jeka  3 , Shengyun Liu  4 , Huaxiang Liu  5 , Malgorzata Miakisz  6 , Jieruo Gu  7 , Lali Kilasonia  8 , Mykola Stanislavchuk  9 , Xiaolei Yang  10 , Yinbo Zhou  10 , Qingfeng Dong  10 , Marian Mitroiu  11 , Janet Addison  12 , Mourad F Rezk  11 , Xiaofeng Zeng  13
Affiliations
Clinical Trial

A phase 3, randomized, double-blind, active-controlled clinical trial to compare BAT1806/BIIB800, a tocilizumab biosimilar, with tocilizumab reference product in participants with moderate-to-severe rheumatoid arthritis with inadequate response to methotrexate: treatment period 2 analysis (week 24 to week 48)

Xiaomei Leng et al. Arthritis Res Ther. .

Abstract

Background: Equivalent efficacy and comparable pharmacokinetic, immunogenicity, and safety profiles of the biosimilar BAT1806/BIIB800 and reference tocilizumab (TCZ) in participants with moderate-to-severe rheumatoid arthritis (RA) have been reported up to week 24 (treatment period [TP] 1) of the phase 3 study. Here we present results for TP2 (study weeks 24-48).

Methods: In this phase 3, multicenter, multiregional, double-blind, active-controlled, equivalence study, participants with active RA despite methotrexate were randomized (1:1:2) to intravenous administration of 8 mg/kg TCZ every 4 weeks to week 48 (TCZ group), or TCZ to week 24 followed by BAT1806/BIIB800 to week 48 (TCZ to BAT1806/BIIB800 group), or BAT1806/BIIB800 to week 48 (BAT1806/BIIB800 group). Efficacy in TP2 was evaluated using American College of Rheumatology (ACR) response criteria (ACR20/50/70) and change from baseline in Disease Activity Score on 28 joints (DAS28). Pharmacokinetics (trough levels), safety, and immunogenicity were also evaluated.

Results: Of 621 randomized participants, 577 (92.9%) completed TP1 and entered TP2 (TCZ: N = 145 [93.5%]; TCZ to BAT1806/BIIB800: N = 142 [92.2%]; BAT1806/BIIB800: N = 290 [92.9%]). Proportions of ACR20 responders were similar between treatment groups throughout TP2 (87.8%, 90.3%, and 90.4%, respectively, at week 48), as were proportions of ACR50 and ACR70 responders, and reduction in DAS28. Drug trough levels and antidrug antibody incidences were comparable between the treatment groups. Adverse events were balanced across the treatment groups and no fatal events were reported.

Conclusion: In TP2, efficacy, safety, immunogenicity, and pharmacokinetic profiles were comparable between the TCZ, TCZ to BAT1806/BIIB800, and BAT1806/BIIB800 groups.

Trial registration: NCT03830203 and EudraCT 2018-002202-31.

Keywords: Biosimilar pharmaceuticals; Rheumatoid arthritis; Tocilizumab; Treatment switching.

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Conflict of interest statement

XL, SJ, SL, HL, MMia, JG, and XZ have no conflicts of interest. PL has received speaker fees from Novartis, AbbVie, UCB, MSD, and GSK; has received support for attending meetings from AbbVie, AstraZeneca, and Medac, and has received a grant for this study from Bio-Thera Solutions Ltd. LK has received speaker fees from Sandoz, Amgen, and Takeda. MS has received speaker fees from Pfizer, Orion, and Boehringer Ingelheim. XY, YZ, and QD are Bio-Thera Solutions Ltd employees and might hold stock, stock options, or both in Bio-Thera Solutions Ltd. MMit, JA, and MFR are Biogen employees and may hold stock, stock options, or both in Biogen.

Figures

Fig. 1
Fig. 1
Trial disposition for TP2. a Eligible participants were randomized (1:1:2) to receive TCZ up to week 48 (TCZ), TCZ up to week 24 followed by BAT1806/BIIB800 up to week 48 (TCZ→BAT1806/BIIB800), or BAT1806/BIIB800 up to week 48 (BAT1806/BIIB800). b Participants were noted as having completed the study if they completed the follow-up visit, regardless of whether they completed TP2 (defined as completing week 48/EOS visit). EOS End of study, TB Tuberculosis, TCZ Tocilizumab reference product, TP2 Treatment period 2
Fig. 2
Fig. 2
Proportions of participants achieving ACR20, ACR50, and ACR70 during TP2 (FAS). Participants were considered as entered into TP2 if the last study drug administration visit was on or after week 24, or participants received the first dose of BAT1806/BIIB800 for the switched group (TCZ→BAT1806/BIIB800). ACR response rates were calculated based on the number of participants with evaluable data at each time point, with data as observed; participants with missing data were considered as nonresponders. FAS included all randomized participants. ACR20/50/70 ≥ 20%/50%/70% response in the American College of Rheumatology criteria, FAS Full analysis set, TCZ Tocilizumab reference product, TP2 Treatment period 2
Fig. 3
Fig. 3
DAS28 (CRP [A] and ESR [B]) for the treatment groups by TP2 visits (FAS). CRP C-reactive protein, DAS28 Disease Activity Score on 28 joints, ESR Erythrocyte sedimentation rate, FAS Full analysis set, SD Standard deviation, TCZ Tocilizumab reference product, TP2 Treatment period 2
Fig. 4
Fig. 4
Sankey plot of ADA status at each visit during TP2: for (A) the TCZ group, (B) the TCZ→BAT1806/BIIB800 group, and (C) the BAT1806/BIIB800 group. ADA Antidrug antibody, TCZ Tocilizumab reference product, TP2 Treatment period 2
See this image and copyright information in PMC

References

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    1. Leng X, Leszczynski P, Jeka S, Liu SY, Liu H, Miakisz M, et al. Comparing tocilizumab biosimilar BAT1806/BIIB800 with reference tocilizumab in patients with moderate-to-severe rheumatoid arthritis with an inadequate response to methotrexate: a phase 3, randomised, multicentre, double-blind, active-controlled clinical trial. Lancet Rheumatol. 2024;6(1):e40–50. 10.1016/S2665-9913(23)00237-0 - DOI - PubMed

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