A randomized, double-blind, two-arm, single-dose, parallel study to compare the pharmacokinetics, pharmacodynamics, safety, and immunogenicity of Bmab 1000 and originator denosumab in healthy male participants.

Abstract

e15001 Background: Bmab 1000 has been approved as a biosimilar to originator denosumab (DENO). This study compared the pharmacokinetics (PK), pharmacodynamics (PD), safety, and immunogenicity of Bmab 1000 and DENO in healthy male participants. Methods: This randomized, double–blind, two–arm, single–dose, Phase 1, parallel study randomized Indian participants 1:1 to a single subcutaneous dose of 35 mg (0.5 mL) Bmab 100 (n=109) or DENO (n=111). A healthy, male–only population ensured a homogenous and sensitive population to detect any product differences. The study included a 3–day in–house stay and 36–week follow–up post dosing. Blood samples were collected at predefined time points for PK, PD, immunogenicity, and safety assessments. Calcium (≥1000 mg/day) and Vitamin D (≥400 IU/day, <1000 IU/day) supplementation was provided throughout to minimize the risk of hypocalcemia. The primary PK parameters were maximum observed serum denosumab concentration (C max ), area under the serum concentration–time curve from time zero to the last quantifiable concentration (AUC 0–t ), and area under the curve extrapolated to infinity (AUC 0–inf ). Bioequivalence was concluded if the 90% confidence intervals for the test/reference geometric least squares mean ratios of the primary PK parameters fell within the predefined acceptance range of 80.00–125.00%. PD and safety were analyzed descriptively. Results: Overall, 220 participants, mean age 40 years, were randomized in the study, of whom 218 received treatment (Bmab 1000, n=107; DENO, n=111). Following treatment, the PK profiles of Bmab 1000 (n=104) and DENO (n=108) were found to be comparable and met bioequivalence (Table). Assessment of the secondary PK endpoints demonstrated similarity between the groups. PD assessments (based on serum C–terminal telopeptide of Type 1 collagen) and immunogenicity evaluations (incidence and titers of anti–drug antibodies) were comparable between treatments. The safety profile of Bmab 1000 was similar to that of DENO. A single fatal event attributed to gastrointestinal symptoms, unrelated to the drug, was reported post dosing with DENO. Conclusions: This study demonstrated PK bioequivalence and comparable PD, safety, and immunogenicity between Bmab 1000 and DENO in healthy male participants. Clinical trial information: CTRI/2024/02/063265. Statistical results of the denosumab primary pharmacokinetics parameters. PK Parameter Geometric Least Squares Means Ratio (Bmab 1000/DENO) 90% Confidence Intervals C max (ng/mL) 105.77 99.30, 112.66 AUC 0–t (ng/mL.h) 106.65 99.51, 114.29 AUC 0–inf (ng/mL.h) 106.71 99.60, 114.32