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  • The Endocrine Society  (3)
  • Basel, Donald  (3)
  • Bober, Michael B  (3)
  • Ozono, Keiichi  (3)
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  • The Endocrine Society  (3)
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  • 1
    Online Resource
    Online Resource
    Persistent and Stable Growth Promoting Effects of Vosoritide in Children With Achondroplasia for up to 2 Years: Results From the Ongoing Phase 3 Extension Study
    The Endocrine Society ; 2021
    In:  Journal of the Endocrine Society Vol. 5, No. Supplement_1 ( 2021-05-03), p. A670-A671
    Details
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 5, No. Supplement_1 ( 2021-05-03), p. A670-A671
    Abstract: Objectives: Vosoritide is a potent stimulator of endochondral bone growth and is in development for the treatment of achondroplasia, the most common form of disproportionate short stature. We previously reported on a 52-week, phase 3, pivotal study that demonstrated a highly statistically significant improvement in annualized growth velocity (AGV) when vosoritide was compared to placebo in children with achondroplasia aged 5-18 years (Savarirayan et al, Lancet, 2020). This is an analysis of data after an additional 52 weeks of treatment in the ongoing phase 3 extension study. Methods: After completion of the phase 3 placebo-controlled study, 119 children were enrolled into the extension study, where they all receive open label 15 μg/kg/day vosoritide. AGV, height Z-score and body proportion ratio were analyzed to assess efficacy of vosoritide in children who were treated with vosoritide for up to 2 years. Fifty-eight continued treatment with vosoritide and 61 switched from placebo to vosoritide. Two participants on continuous vosoritide treatment discontinued before the Week 52 timepoint. Four participants on continuous vosoritide treatment and 7 participants who switched from placebo to vosoritide missed the Week 52 assessment due to Covid-19. Results: In children randomized to receive daily vosoritide, baseline mean (SD) AGV was 4.26 (1.53) cm/year. After the first 52 weeks of treatment, mean (SD) AGV was 5.67 (0.98) cm/year. Mean (SD) AGV over the second year was 5.57 (1.10) cm/year. Mean (SD) change from baseline in height Z-score improved by +0.24 (0.31) at Week 52 in the pivotal study and +0.45 (0.56) at Week 52 in the extension study. Mean (SD) upper-to-lower body segment ratio improved with a change from baseline of -0.03 (0.11) at Week 52 in the pivotal study and -0.09 (0.11) at Week 52 in the extension study. In children who switched from placebo to vosoritide after 52 weeks, baseline AGV was 4.06 (1.20) cm/year and 3.94 (1.07) cm/year after 52 weeks on placebo. In the second year, after receiving 52 weeks of vosoritide, mean AGV was 5.65 (1.47) cm/year, the mean (SD) change in height Z-score was +0.24 (0.34), and the change in upper-to-lower body segment ratio was -0.03 (0.08). No new adverse events associated with vosoritide treatment were detected with up to 2 years of continuous daily, subcutaneous treatment. Most adverse events were mild and no serious adverse events were attributed to vosoritide. The most common adverse event remains mild and transient injection site reactions. Conclusions: The effect of vosoritide administration on growth as measured through AGV and height Z-score was maintained for up to 2-years in children with achondroplasia aged 5 to 18 years, with an improvement of body proportions.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    URL: Article
    DOI: 10.1210/jendso/bvab048.1368
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
    detail.hit.zdb_id: 2881023-5
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    Online Resource
  • 2
    Online Resource
    Online Resource
    LBMON196 A Randomized Controlled Trial Of Vosoritide In Infants And Toddlers With Achondroplasia
    The Endocrine Society ; 2022
    In:  Journal of the Endocrine Society Vol. 6, No. Supplement_1 ( 2022-11-01), p. A591-A592
    Details
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 6, No. Supplement_1 ( 2022-11-01), p. A591-A592
    Abstract: Vosoritide increases annualized growth velocity (AGV) in children with achondroplasia aged 5 to 18 years. This global, phase 2, randomized, double-blind, placebo-controlled study evaluated the safety and efficacy of vosoritide on growth in children with achondroplasia aged 3 months to & lt;5 years. Methods This study compared once-daily subcutaneous administration of vosoritide, at doses of 15 or 30 μg/kg of body weight, with placebo. Eligible patients had participated, for up to 6 months, in an observational growth study to calculate their baseline AGV. The primary objective was to evaluate the safety and tolerability of vosoritide in children with achondroplasia. The primary efficacy evaluation was the change from baseline in height Z-score versus placebo at week 52 using an ANCOVA model. Secondary efficacy analyses included change from baseline in AGV and upper-to-lower body segment ratio versus placebo at Week 52 using an ANCOVA model. Results A total of 75 patients were enrolled, with 11 sentinel subjects who received vosoritide to establish PK and safety. A further 32 were randomized to receive vosoritide and 32 to receive placebo. A total of 73 patients completed the 52-week trial. All patients reported at least one adverse event. Four serious adverse events occurred with vosoritide and 8 with placebo, none were treatment-related. Two participants discontinued, one on vosoritide with pre-existing respiratory morbidity who had a fatal respiratory arrest and one on placebo who withdrew consent. In the full analysis population, vosoritide (n=43) compared to placebo (n=32), increased height Z-score by 0.30 SD (95% CI 0. 07, 0.54); increased AGV by 0.92cm/year (95% CI 0.24, 1.59); and did not worsen upper-to-lower body segment ratio which changed by -0. 06 (95% CI -0.15, 0. 03). Conclusions Daily, subcutaneous administration of vosoritide to young children with achondroplasia was safe and resulted in increases in height Z-score and AGV. (Funded by BioMarin; ClinicalTrials.gov NCT03583697) Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    URL: Article
    DOI: 10.1210/jendso/bvac150.1225
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2022
    detail.hit.zdb_id: 2881023-5
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  • 3
    Online Resource
    Online Resource
    SAT-LB18 A Randomized Controlled Trial of Vosoritide in Children With Achondroplasia
    The Endocrine Society ; 2020
    In:  Journal of the Endocrine Society Vol. 4, No. Supplement_1 ( 2020-05-08)
    Details
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 4, No. Supplement_1 ( 2020-05-08)
    Abstract: Background: Achondroplasia is a disorder caused by specific mutations in the gene encoding the fibroblast growth factor receptor 3 (FGFR3) protein. Open-label, phase 2 trials in children with achondroplasia showed that administration of vosoritide, an analogue of C-natriuretic peptide, resulted in sustained increases in annualized growth velocity. Methods: This international, randomized, double-blind, phase 3 trial compared once-daily subcutaneous administration of vosoritide, at a dose of 15 μg per kg of body weight, with placebo in children with achondroplasia aged 5 to & lt;18 years. Eligible patients had participated, for at least 6 months, in an observational growth study in order to calculate their baseline annualized growth velocity. The primary efficacy endpoint was the change from baseline in annualized growth velocity at week 52 of treatment. The primary analysis of the change from baseline in annualized growth velocity was performed using an ANCOVA model. Results: A total of 121 patients were randomized, with 60 assigned to receive vosoritide and 61 to receive placebo. A total of 119 patients completed the 52-week trial. The adjusted mean difference in annualized growth velocity between patients administered vosoritide and those administered placebo was 1.57 cm per year in favor of vosoritide (95% CI: [1.22, 1.93], two-sided p-value & lt;0.001). A total of 119 patients experienced at least one adverse event (vosoritide group, 59 [98.3%], placebo group, 60 [98.4%] ). Conclusions: Daily, subcutaneous administration of vosoritide to children with achondroplasia resulted in a significant increase in mean annualized growth velocity and similar incidence of adverse events compared to placebo.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    URL: Article
    DOI: 10.1210/jendso/bvaa046.2081
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
    detail.hit.zdb_id: 2881023-5
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    Online Resource
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