Rationale, design, and methods of a randomized, controlled, open-label clinical trial with open-label extension to investigate the safety of vosoritide in infants, and young children with achondroplasia at risk of requiring cervicomedullary decompression surgery.
Rationale, design, and methods of a randomized, controlled, open-label clinical trial with open-label extension to investigate the safety of vosoritide in infants, and young children with achondroplasia at risk of requiring cervicomedullary decompression surgery.
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DOI：
10.1177/00368504211003782
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发表时间：
2021-01
期刊：
影响因子：
2.1
通讯作者：
Day, Jonathan R. S.
中科院分区：
文献类型：
--
作者：
Savarirayan, Ravi;Irving, Melita;Maixner, Wirginia;Thompson, Dominic;Offiah, Amaka C.;Connolly, Daniel J. A.;Raghavan, Ashok;Powell, James;Kronhardt, Marcin;Jeha, George;Ghani, Sajda;Fisheleva, Elena;Day, Jonathan R. S.
软骨发育不全导致枕骨大孔和椎管狭窄，导致婴儿颈髓压迫导致死亡率增加，成年后椎管狭窄导致发病率显著增加。Vosoritide是一种C-利钠肽类似物，已被证明可改善软骨发育不全儿童的软骨内骨化。本试验的目的是评价vosoritide的安全性，以及vosoritide是否可以改善可能需要减压手术的儿童枕骨大孔和椎管的生长。将使用枕骨大孔软骨发育不全评分来识别需要减压手术的婴儿。这是一项在0至≤12个月的软骨发育不全婴儿中进行的为期2年的vosoritide开放标签随机对照试验。将约20名婴儿以1：1的比例随机分配至开放标签每日一次皮下注射vosoritide联合标准治疗组或单独标准治疗组。本研究的主要和次要目的是评价vosoritide在需要减压手术的颈髓压迫儿童中的安全性和有效性。本试验将在专门的骨骼发育不良治疗中心进行，这些中心具有完善的多学科护理途径和颈内侧压迫神经外科治疗的标准化方法。2年后，随机分配至单独标准治疗组的婴儿将有资格转换至vosoritide+标准治疗组，再持续3年。这项开创性的试验希望解决一个重要的问题，即在需要颈髓减压手术的婴儿早期使用vosoritide治疗是否安全，并且可以改善枕骨大孔和椎管的生长，缓解狭窄。这反过来可能会减少周围结构的压迫，包括神经轴和脊髓，这可能会减轻未来的发病率和死亡率。试验注册：ClinicalTrials.gov，NCT 04554940; EudraCT编号，2020-001055-40
Achondroplasia causes narrowing of the foramen magnum and the spinal canal leading to increased mortality due to cervicomedullary compression in infants and significant morbidity due to spinal stenosis later in adulthood. Vosoritide is a C-natriuretic peptide analogue that has been shown to improve endochondral ossification in children with achondroplasia. The objective of this trial is to evaluate the safety of vosoritide and whether vosoritide can improve the growth of the foramen magnum and spinal canal in children that may require decompression surgery. An Achondroplasia Foramen Magnum Score will be used to identify infants at risk of requiring decompression surgery. This is a 2-year open label randomized controlled trial of vosoritide in infants with achondroplasia ages 0 to ≤12 months. Approximately 20 infants will be randomized 1:1 to either open label once daily subcutaneous vosoritide combined with standard of care or standard of care alone. The primary and secondary aims of the study are to evaluate the safety and efficacy of vosoritide in children with cervicomedullary compression at risk of requiring decompression surgery. The trial will be carried out in specialized skeletal dysplasia treatment centers with well established multidisciplinary care pathways and standardized approaches to the neurosurgical management of cervicomedually compression. After 2 years, infants randomized to standard of care alone will be eligible to switch to vosoritide plus standard of care for an additional 3 years. This pioneering trial hopes to address the important question as to whether treatment with vosoritide at an early age in infants at risk of requiring cervicomedullary decompression surgery is safe, and can improve growth at the foramen magnum and spinal canal alleviating stenosis. This in turn may reduce compression of surrounding structures including the neuraxis and spinal cord, which could alleviate future morbidity and mortality. Trial registrations: ClinicalTrials.gov, NCT04554940; EudraCT number, 2020-001055-40
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