Murdoch Children's Research Institute, Royal Children's Hospital, and University of Melbourne, Parkville, Victoria, Australia.
Guy's and St. Thomas' NHS Foundation Trust, Evelina Children's Hospital, London, UK.
Sci Prog. 2021 Jan-Mar;104(1):368504211003782. doi: 10.1177/00368504211003782.
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. ClinicalTrials.gov, NCT04554940; EudraCT number, 2020-001055-40.
软骨发育不全导致颅后窝和椎管狭窄，导致婴儿因颈髓受压而死亡率增加，成年后因脊柱狭窄而发病率显著增加。Vosoritide 是一种 C 型利钠肽类似物，已被证明可改善软骨发育不全儿童的软骨内骨化。本试验的目的是评估 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颅后窝和椎管的生长。使用软骨发育不全颅后窝评分来识别有需要减压手术风险的婴儿。这是一项为期 2 年的软骨发育不全婴儿开放标签随机对照试验，0 至≤12 个月龄的婴儿接受 vosoritide 治疗。大约 20 名婴儿将按 1:1 随机分为每日皮下注射 vosoritide 联合标准治疗或标准治疗。该研究的主要和次要目的是评估 vosoritide 在有颈髓受压风险需要减压手术的儿童中的安全性和疗效。试验将在专门的骨骼发育不良治疗中心进行，这些中心有成熟的多学科护理途径和标准化的神经外科治疗颈髓受压的方法。2 年后，单独接受标准治疗的婴儿有资格转为接受 vosoritide 加标准治疗，再治疗 3 年。这项开创性的试验希望解决一个重要问题，即在有颈髓减压手术风险的婴儿中，早期使用 vosoritide 是否安全，以及是否可以改善颅后窝和椎管的生长，从而缓解狭窄。这反过来又可以减轻对周围结构的压迫，包括神经轴和脊髓，从而减轻未来的发病率和死亡率。ClinicalTrials.gov，NCT04554940；EudraCT 编号，2020-001055-40。
