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Pharmacokinetics, Immunogenicity and Safety Study for SHR-1309 Injection and Perjeta® in Healthy Chinese Male Volunteers.

ABSTRACT: Objectives: Pertuzumab is a monoclonal antibody for the treatment of breast cancer. The aim of this study was to compare the pharmacokinetics, immunogenicity and safety of the test preparation SHR-1309 injecta and the reference preparation Perjeta® in healthy Chinese male subjects. Methods: In this randomized, double-blind, single dose, two-way, parallel bioequivalence trial, a total of 80 qualified Chinese male subjects were selected and randomly divided into two groups. Each subject was intravenously injected with SHR-1309 or Perjeta®. Blood samples were collected at 21 different time points for pharmacokinetic analysis. In addition, immunogenicity was assessed at five different time points. The safety of the medication was monitored throughout the whole trial. Results: C_max and AUC_0-t were the primary pharmacokinetic parameters. Under a 90% confidence interval, their geometric mean ratios were 98.30 and 88.41% for SHR-1309 injection and Perjeta®, respectively. The geometric mean ratio of secondary pharmacokinetic parameters AUC_0-∞ was 88.58%. These evaluation indexes are in the standard range of 80-125%, so SHR-1309 can be considered bioequivalent to Perjeta®. After 1,680 h (day 70) of administration, the two groups had 12 and 13 subjects who produced antidrug antibody (ADA), respectively. The occurrence time and proportion of ADA in SHR-1309 and Perjeta® were similar between subjects, and they had similar immunogenicity. During the entire trial period, there were 71 drug-related adverse reactions in 29 subjects who received SHR-1309 and 61 drug-related adverse reactions in 32 subjects who received Perjeta®. The incidence of adverse reactions between the two drugs was similar. Conclusion: The pharmacokinetic parameters, immunogenicity and safety of the biosimilar SHR-1309 injection produced by Shanghai Hengrui Pharmaceutical Co. Ltd. were similar to the original drug Perjeta® produced by Roche Pharma AG. The two drugs met the bioequivalence evaluation criteria. Therefore, SHR-1309 is bioequivalent to Perjeta®. Clinical trial registration: CTR20200,738.

SUBMITTER: Cui Y

PROVIDER: S-EPMC8207516 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:This study aimed to assess and compare the pharmacokinetic (PK) and pharmacodynamic (PD) properties following a single subcutaneous injection of epoetin alfa (Eporon®) with those of the comparator (Eprex®) in healthy male subjects.A randomized, double-blind, two-sequence, crossover study was conducted. Subjects were randomly assigned to receive a single dose, that is, 4,000 IU, of the test or comparator epoetin alfa. After 4 weeks, all subjects received the alternative formulation. The primary PK parameters, maximum observed concentration (Cmax) and area under the curve extrapolated to infinity (AUCinf), were calculated with the serum erythropoietin (EPO) concentrations from blood samples collected for 144 h after dosing. The reticulocyte, hematocrit, hemoglobin and red blood cell counts were measured up to 312 h as PD markers. The primary PD parameters, maximum observed effect (Emax) and area under the effect curve (AUEC), were obtained from the baseline-corrected reticulocyte count. The serum EPO concentration and the reticulocyte count were used to assess the concentration-response relationship. The tolerability and immunogenicity profiles were assessed together.Forty-two subjects completed the study. The mean EPO concentration-time profiles were comparable between the two formulations. The geometric mean ratios (90% CI) of the Cmax and AUCinf were 0.908 (0.843-0.978) and 1.049 (0.999-1.101), respectively, both of which were within the regulatory range of 0.80-1.25. Additionally, the PD and tolerability profiles were similar between the two formulations. The time-matched serum EPO concentration and PD markers presented a counterclockwise hysteresis, suggesting a time delay between the measured concentration and the response. Both formulations were well tolerated, and production of anti-drug antibodies was not observed.The two epoetin alfa formulations had similar PK, PD and tolerability profiles. Furthermore, both formulations had a similar time-matched serum EPO concentration and erythropoietic response profile. Thus, the two formulations are expected to be used interchangeably in clinical settings.

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Pharmacokinetics, Immunogenicity and Safety Study for SHR-1309 Injection and Perjeta® in Healthy Chinese Male Volunteers.

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