| Title: |
A Randomized Phase 1 Study Comparing the PK, PD, Safety, and Immunogenicity of Proposed Biosimilar RGB-14-X and Denosumab in Healthy Adult Males |
| Authors: |
Biver, Emmanuel; Body, Jean-Jacques; Sachdeva, Ashwin; Študentová, Hana; Nagy, Zsuzsanna; Kun, Attila; Horvát-Karajz, Károly; Kiefer, Joachim; Pap, Tímea; Jókai, Enikő; Vasas, Ferenc Béla; Seefried, Lothar |
| Source: |
ISSN: 1752-8054 ; Clinical and translational science, vol. 19, no. 2 (2026) e70468. |
| Publication Year: |
2026 |
| Collection: |
Université de Genève: Archive ouverte UNIGE |
| Subject Terms: |
info:eu-repo/classification/ddc/616; Adverse events; Bioequivalence; Healthy subjects; Monoclonal antibodies; Pharmacodynamics; Pharmacokinetics‐pharmacodynamics; Humans; Male; Denosumab / pharmacokinetics; Denosumab / administration & dosage; Denosumab / adverse effects; Denosumab / immunology; Denosumab / pharmacology; Biosimilar Pharmaceuticals / pharmacokinetics; Biosimilar Pharmaceuticals / administration & dosage; Biosimilar Pharmaceuticals / adverse effects; Biosimilar Pharmaceuticals / pharmacology; Adult; Double-Blind Method; Middle Aged; Healthy Volunteers; Young Adult; Area Under Curve; Injections; Subcutaneous; Therapeutic Equivalency; Bone Density Conservation Agents / pharmacokinetics; Bone Density Conservation Agents / administration & dosage; Bone Density Conservation Agents / adverse effects |
| Description: |
Denosumab is a monoclonal antibody targeting the receptor activator of nuclear factor kappa-b ligand widely used for the prevention of skeletal-related events in patients with bone metastases. This Phase 1 randomized, double-blind, two-arm, parallel-group study assessed the equivalence in pharmacokinetics (PK) and compared the pharmacodynamics (PD), safety, and immunogenicity of the proposed biosimilar RGB-14-X and reference denosumab in healthy males. Participants were randomized 1:1 to a single subcutaneous 60 mg dose of RGB-14-X or reference denosumab, with 252 days of follow-up. Primary PK endpoints were maximum observed serum concentration (C max ) and area under the concentration-time curve from time 0 to last quantifiable concentration (AUC 0-last ) and extrapolated to infinity (AUC 0-inf ). Secondary objectives were to compare additional PK parameters, safety and tolerability, PD and immunogenicity between groups. Of 165 participants randomized, 162 (98.2%) completed the study. The geometric mean ratios and corresponding 90% confidence intervals of RGB-14-X versus reference denosumab for C max , AUC 0-last , and AUC 0-inf were within the pre-specified range of 0.80-1.25, demonstrating equivalence. No notable differences were observed in secondary PK or PD parameters between groups; maximum reduction in concentration of the bone resorption marker serum C-terminal telopeptide of type I collagen (CTX) and the extent and duration of reduction in CTX levels over time were similar. RGB-14-X was well tolerated with a similar safety profile to reference denosumab. No anti-drug or neutralizing antibodies were detected in either group. RGB-14-X demonstrated biosimilarity to reference denosumab, with equivalent PK and similar PD, safety, and immunogenicity outcomes in healthy males. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/41703781; unige:192200 |
| Availability: |
https://archive-ouverte.unige.ch/unige:192200 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.6EBD5B0D |
| Database: |
BASE |