College of Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Krakowskie Centrum Medyczne, Kraków, Poland.
Osteoporos Int. 2024 Nov;35(11):1919-1930. doi: 10.1007/s00198-024-07161-x. Epub 2024 Jul 23.
This 78-week (18-month) study conducted in 479 postmenopausal women with osteoporosis evaluated the efficacy, pharmacodynamics, pharmacokinetics, safety, and immunogenicity of candidate biosimilar CT-P41 relative to US reference denosumab. CT-P41 had equivalent efficacy and pharmacodynamics to US-denosumab, with similar pharmacokinetics and comparable safety and immunogenicity profiles.
To demonstrate equivalence of candidate biosimilar CT-P41 and US reference denosumab (US-denosumab) in postmenopausal women with osteoporosis.
This 78-week (18-month), double-blind, randomized, active-controlled Phase 3 study (NCT04757376) comprised two treatment periods (TPs). In TPI, patients (N = 479) were randomized 1:1 to 60 mg subcutaneous CT-P41 or US-denosumab. At Week 52, those who had received CT-P41 in TPI continued to do so. Those who had received US-denosumab were randomized (1:1) to continue treatment or switch to CT-P41 in TPII. The primary efficacy endpoint was percent change from baseline in lumbar spine bone mineral density at Week 52. Efficacy equivalence was concluded if associated 95% confidence intervals (CI) for least squares (LS) mean group differences fell within ± 1.503%. The primary pharmacodynamic (PD) endpoint was area under the effect curve for serum carboxy-terminal cross-linking telopeptide of type I collagen through the first 26 weeks, with an equivalence margin of 80-125% (for 95% CIs associated with geometric LS mean ratios).
Equivalence was demonstrated for CT-P41 and US-denosumab with respect to primary efficacy (LS mean difference [95% CI]: - 0.139 [- 0.826, 0.548] in the full analysis set and - 0.280 [- 0.973, 0.414] in the per-protocol set) and PD (geometric LS mean ratio [95% CI]: 94.94 [90.75, 99.32]) endpoints. Secondary efficacy, PD, pharmacokinetics, and safety results were comparable among all groups up to Week 78, including after transitioning to CT-P41 from US-denosumab.
CT-P41 was equivalent to US-denosumab in women with postmenopausal osteoporosis, with respect to primary efficacy and PD endpoints.
证明候选生物类似药 CT-P41 与美国参考地舒单抗（US-denosumab）在绝经后骨质疏松症女性中的等效性。
这是一项为期 78 周（18 个月）的双盲、随机、活性对照的 3 期研究（NCT04757376），包括两个治疗期（TP）。在 TPI 中，患者（N=479）按 1:1 随机接受 60mg 皮下 CT-P41 或 US-denosumab。在第 52 周时，那些在 TPI 中接受 CT-P41 治疗的患者继续接受治疗。那些接受 US-denosumab 治疗的患者在 TPII 中按 1:1 随机继续治疗或换用 CT-P41。主要疗效终点是第 52 周时腰椎骨密度相对于基线的变化百分比。如果最小二乘（LS）均值组间差异的相关 95%置信区间（CI）落在±1.503%范围内，则认为等效。主要药效学（PD）终点是第 1 至 26 周时血清 I 型胶原羧基末端交联肽的效应曲线下面积，等效幅度为 80-125%（与几何 LS 均值比相关的 95%CI）。
在主要疗效（全分析集的 LS 均值差值[95%CI]：-0.139[-0.826，0.548]；符合方案集的 LS 均值差值：-0.280[-0.973，0.414]）和 PD（几何 LS 均值比[95%CI]：94.94[90.75，99.32]）终点方面，CT-P41 与 US-denosumab 等效。直至第 78 周，次要疗效、PD、药代动力学和安全性结果在所有组中均相似，包括从 US-denosumab 转换为 CT-P41 后。
在绝经后骨质疏松症女性中，CT-P41 与 US-denosumab 相比，在主要疗效和 PD 终点方面等效。
