A phase I, randomized, double-blinded, single-dose study evaluating the pharmacokinetic equivalence of the biosimilar IBI305 and bevacizumab in healthy male subjects

Zhang, Hong; Zhu, Xiaodong; Wei, Haijing; Li, Cuiyun; Chen, Hong; Li, Xiaojiao; Wu, Min; Liu, Jingrui; Chen, Guiling; Zhou, Hui; Zheng, Shirui; Ding, Yanhua

doi:10.5414/cp203349

Cited by 11 publications

(12 citation statements)

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“…The treatment group ratios of LS geometric means for the three primary PK parameters were fully contained within the bioequivalence limits of 80–125%. These results were consistent with other similar studies in Caucasian, Japanese, Korean, and Chinese healthy volunteers ( Table 5 ) (Knight et al, 2016; Hettema et al, 2017; Markus et al, 2017; Tajima et al, 2017; Hanes et al, 2018; Zhang et al, 2018; Cho et al, 2019; Wu et al, 2019; Zhang et al, 2019).…”

Section: Discussionsupporting

confidence: 93%

“…TEAEs considered related to the study drug in this study were reported for 19 (38.8%) subjects in the TAB008 group and 19 (38.0%) subjects in the Avastin ® group. AE seemed to vary widely between these studies (Knight et al, 2016; Hettema et al, 2017; Markus et al, 2017; Tajima et al, 2017; Hanes et al, 2018; Zhang et al, 2018; Cho et al, 2019; Wu et al, 2019; Zhang et al, 2019), but there was no significant correlation with the dose. The %AE with 1 mg/kg ranged across studies from 33.3% to 55.0% for biosimilars and 32.3% to 48.8% for Avastin ® (EU-sourced).…”

Section: Discussionmentioning

confidence: 87%

“…The %AE with 3 mg/kg ranged across studies from 8.3% to 56.4% for biosimilars and 4.2% to 63.2% for Avastin ® (EU-sourced). The %AE with 5 mg/kg ranged across studies from 19.6% to 48.5% for biosimilars and 42.6% to 62.9% for Avastin ® (EU-sourced) ( Table 5 ) (Knight et al, 2016; Hettema et al, 2017; Markus et al, 2017; Tajima et al, 2017; Hanes et al, 2018; Zhang et al, 2018; Cho et al, 2019; Wu et al, 2019; Zhang et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

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A Phase I, Randomized, Single-Dose Study Evaluating the Biosimilarity of TAB008 to Bevacizumab in Healthy Volunteers

Wang

Лонг

et al. 2019

Front. Pharmacol.

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Objective: This study compared the pharmacokinetics (PK), safety, and immunogenicity of the biosimilar TAB008 monoclonal antibody to bevacizumab (Avastin ® ) in normal healthy Chinese male volunteers. Methods: In this randomized, double-blind, parallel controlled study, a total of 100 healthy Chinese male subjects were randomized (1:1) to receive a single 1 mg/kg intravenous dose of TAB008 or Avastin ® over a 90-min infusion. The subjects were followed for 99 days after drug administration. Primary endpoints were bioequivalence of major pharmacokinetic parameters (AUC 0-t and AUC 0-∞ ) and maximum observed serum concentration (C max ). Secondary endpoints included safety and immunogenicity parameters. Results: The two groups of test subjects (49 subjects in the TAB008 group and 50 subjects in the Avastin ® group) were well matched in regards to all demographic and baseline characteristics. The treatment group ratios of LS geometric means for the three primary PK parameters were fully contained within the bioequivalence limits of 80.00–125.00% (90% CI was 103.66–118.33% for C max , 94.32–111.72% for AUC 0-t , and 94.69–112.23% for AUC 0-∞ ). Treatment-emergent adverse events (TEAEs) were reported for 24 (49.0%) subjects in the TAB008 group and 22 (44.0%) subjects in the Avastin ® group. TEAEs related to the study drug were reported for 19 (38.8%) subjects in the TAB008 group and 19 (38.0%) subjects in the Avastin ® group. National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade 3 TEAEs were reported for 1 (2.0%) subject in the TAB008 group and 3 (6.0%) subjects in the Avastin ® group. There were no Grade 4 or 5 TEAEs or serious adverse events (SAEs) during the study. Anti-drug antibody generation was reported once only in each group, and neutralizing antibody (Nab) analysis was negative upon follow-up. Conclusion: TAB008 attained pharmacokinetic similarity to bevacizumab, and was safe and well tolerated.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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A Phase I, Randomized, Single-Dose Study Evaluating the Biosimilarity of TAB008 to Bevacizumab in Healthy Volunteers

Wang

Лонг

et al. 2019

Front. Pharmacol.

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“…Moreover, results confirm that bevacizumab-EU and bevacizumab-US are bioequivalent to each other, consistent with results from other phase I studies of bevacizumab biosimilars [16,17]. The PK results of this study are consistent with those of other phase I PK studies of (proposed) bevacizumab biosimilars which also demonstrated equivalence to the reference product [16][17][18][19][20][21][22][23][24][25][26]. However, direct comparisons of absolute PK parameters values between studies are generally not appropriate due to differences between the doses used (1 mg/kg, 3 mg/kg or 5 mg/kg), sample collection, and assessment methods [16][17][18][19][20][21][22][23][24][25][26].…”

Section: Discussionsupporting

confidence: 89%

A phase I, randomized, single-dose pharmacokinetic study comparing sb8 (bevacizumab biosimilar) with reference bevacizumab in healthy volunteers

Shin

Lee

Choi

et al. 2020

Cancer Chemother Pharmacol

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Purpose To compare pharmacokinetics, safety, tolerability, and immunogenicity between SB8, a bevacizumab biosimilar, and the European Union (EU) and United States (US) reference products (bevacizumab-EU, bevacizumab-US). Methods In this randomized, double-blind, parallel-group, and single-dose study, healthy volunteers were randomized to receive a 3 mg/kg dose of SB8, bevacizumab-EU, or bevacizumab-US via intravenous infusion. Primary endpoints were area under the concentration–time curve from time zero to infinity (AUCinf) and to the last quantifiable concentration (AUClast), and maximum observed serum concentration (Cmax). Bioequivalence was achieved if 90% confidence intervals (CIs) for the ratios of the geometric least squares means (LSMeans) of primary endpoints were within the predefined bioequivalence margins of 80.00–125.00%. Safety and immunogenicity were also investigated. Results The 90% CIs for the geometric LSMean ratios of AUCinf, AUClast and Cmax were all within the prespecified bioequivalence margins. Geometric LSMean ratios for SB8/bevacizumab-EU, SB8/bevacizumab-US and bevacizumab-EU/bevacizumab-US were 88.01%, 88.48% and 100.54% for AUCinf, 88.65%, 89.08% and 100.49% for AUClast and 99.59%, 101.15% and 101.56% for Cmax, respectively. Incidence of treatment-emergent adverse events (TEAEs) across treatment groups was comparable (SB8: 50.0%, bevacizumab-EU: 37.5%, bevacizumab-US: 53.8%). Most TEAEs were mild and considered as not related to the study drug. No deaths or treatment discontinuations due to adverse events occurred. Incidence of anti-drug antibodies was also comparable between all groups and no neutralizing antibodies were detected. Conclusion This study demonstrated pharmacokinetic bioequivalence and similar safety and immunogenicity profiles of SB8 to both reference products, bevacizumab-EU and bevacizumab-US, and of bevacizumab-EU to bevacizumab-US. Clinicaltrials.gov identifier NCT02453672 (submitted date); EudraCT number: 2015-001,026-41.

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“…Biosimilars are defined as biologic medical products that are highly similar to an approved reference product, notwithstanding minor clinically insignificant differences [8,9]. The clinical needs for affordable bevacizumab treatment have resulted in the development of a number of biosimilar molecules [10][11][12][13][14][15][16][17][18][19][20][21]. As of August 2020, two bevacizumab biosimilars (Zirabev ® and Mvasi ® ) have been approved by the United States Food and Drug Administration (FDA) [22,23] and the European Medicines Agency (EMA) [24,25], and two (Byvasda ® and Ankada ® ) by the Chinese National Medical Products Administration (NMPA) [26,27].…”

Section: Introductionmentioning

confidence: 99%

A phase 1 randomized study compare the pharmacokinetics, safety and immunogenicity of HLX04 to reference bevacizumab sourced from the United States, the European Union, and China in healthy Chinese male volunteers

Zhu

Sun

et al. 2021

Cancer Chemother Pharmacol

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Purpose To compare the pharmacokinetic profiles, safety and immunogenicity of proposed bevacizumab biosimilar HLX04 with reference bevacizumab in healthy Chinese males. Methods In this double-blind Phase 1 study, healthy volunteers (N = 208) were randomized 1:1:1:1 to a single 3 mg/kg intravenous infusion of HLX04 or reference bevacizumab sourced from the United States (bevacizumab-US), the European Union (bevacizumab-EU) or China (bevacizumab-CN). Co-primary endpoints were area under the serum concentration–time profile (AUC) from time zero extrapolated to infinity (AUC0–inf) and from zero to last quantifiable concentration (AUClast). Secondary endpoint was the maximum serum drug concentration (Cmax). Study participants were monitored for treatment-emergent adverse events (TEAEs) and samples were collected for anti-drug antibody (ADA) testing throughout the study. Results Pharmacokinetic parameters were similar across groups. The respective geometric least-squares mean ratios (GLSMR) of AUC0–inf, AUClast and Cmax were: 95.7%, 96.0% and 101.8% for HLX04 versus bevacizumab-US; 94.3%, 94.6% and 100.5% for HLX04 versus bevacizumab-EU; and 90.0%, 90.4% and 98.2% for HLX04 versus bevacizumab-CN. For all test-to-reference comparisons, two-sided 90% confidence intervals of GLSMR for AUC0–inf, AUClast and Cmax fell in the pre-specified bioequivalence range (80–125%). There were no notable differences in the frequency, nature and/or grade of TEAEs. No deaths were reported and no ADAs were detected during the study. Conclusion HLX04 had similar safety and pharmacokinetic profiles to reference bevacizumab in healthy Chinese males, supporting the confirmatory Phase 3 study investigating the efficacy and safety equivalence between HLX04 and bevacizumab in patients with metastatic colorectal cancer (NCT03511963). Clinical trial registration The study was registered with Clinicaltrials.gov, NCT03483649.

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A phase I, randomized, double-blinded, single-dose study evaluating the pharmacokinetic equivalence of the biosimilar IBI305 and bevacizumab in healthy male subjects

Cited by 11 publications

References 0 publications

A Phase I, Randomized, Single-Dose Study Evaluating the Biosimilarity of TAB008 to Bevacizumab in Healthy Volunteers

A Phase I, Randomized, Single-Dose Study Evaluating the Biosimilarity of TAB008 to Bevacizumab in Healthy Volunteers

A phase I, randomized, single-dose pharmacokinetic study comparing sb8 (bevacizumab biosimilar) with reference bevacizumab in healthy volunteers

A phase 1 randomized study compare the pharmacokinetics, safety and immunogenicity of HLX04 to reference bevacizumab sourced from the United States, the European Union, and China in healthy Chinese male volunteers

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