Efficacy and safety of candidate biosimilar CT-P41 versus reference denosumab: a double-blind, randomized, active-controlled, Phase 3 trial in postmenopausal women with osteoporosis.

Autor:	Reginster, Jean-Yves, Czerwinski, Edward, Wilk, Krzysztof, Borowy, Przemysław, Strzelecka, Anna, Budlewski, Tomasz, Janowska-Maus, Monika, Szymanowski, Krzysztof, Kwiatek, Joanna, Postol, Svitlana, Põder, Airi, Supronik, Jerzy, Kim, SungHyun, Suh, JeeHye, Han, NooRi, Kim, NaHyun, Bae, SeoHee, Silverman, Stuart L.
Předmět:	THERAPEUTIC use of monoclonal antibodies PATIENT safety BODY mass index BONE density STATISTICAL sampling BLIND experiment BIOLOGICAL products POSTMENOPAUSE RANDOMIZED controlled trials DESCRIPTIVE statistics MONOCLONAL antibodies DISEASES DRUG efficacy OSTEOPOROSIS WOMEN'S health CONFIDENCE intervals
Zdroj:	Osteoporosis International; Nov2024, Vol. 35 Issue 11, p1919-1930, 12p
Abstrakt:	Summary: 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. Purpose: To demonstrate equivalence of candidate biosimilar CT-P41 and US reference denosumab (US-denosumab) in postmenopausal women with osteoporosis. Methods: 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). Results: 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. Conclusions: CT-P41 was equivalent to US-denosumab in women with postmenopausal osteoporosis, with respect to primary efficacy and PD endpoints. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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