Bright George M, Do Minh-Ha T, McKew John C, Blum Werner F, Thorner Michael O
Lumos Pharma, Inc., 4200 Marathon Blvd., Suite 200, Austin, Texas 78756, USA.
Center of Child and Adolescent Medicine, Justus-Liebig University, 35390 Giessen, Germany.
J Endocr Soc. 2021 Feb 25;5(6):bvab030. doi: 10.1210/jendso/bvab030. eCollection 2021 Jun 1.
We hypothesize, based on the degree of residual hypothalamic-pituitary function, that some, but not all, children with growth hormone deficiency (GHD) may have beneficial growth responses to the orally administered growth hormone (GH) secretagogue LUM-201.
To determine if pretreatment testing can identify predictive enrichment markers (PEM) for subjects with adequate residual function who are responsive to LUM-201.
We performed an analysis of a completed, randomized, placebo-controlled trial of LUM-201, a GH secretagogue receptor agonist, in which all randomized subjects had pretreatment testing. This international multicenter study conducted in pediatric endocrinology clinics included 68 naïve-to-treatment, prepubertal children with established diagnoses of GHD. Outcome measures included the sensitivity, specificity, and predictive accuracy of potential markers to predict 6-month growth responses to oral LUM-201 and daily rhGH.
Two PEM were identified for use in defining PEM-positive status: (1) baseline insulin-like growth factor I (IGF-I) concentration >30 ng/mL and (2) peak GH response of ≥5 ng/mL upon administration of single-dose LUM-201. PEM-positive status enriches a population for better growth responses to LUM-201. PEM-negative status enriches a population for better growth responses to rhGH.
Combined, the peak GH response to single-dose LUM-201 and the baseline IGF-I concentration are effective PEMs for 6-month growth responses to LUM-201 and rhGH in prepubertal children with GHD.
基于残余下丘脑 - 垂体功能的程度，我们推测部分（而非全部）生长激素缺乏症（GHD）儿童可能对口服生长激素（GH）促分泌剂LUM - 201有有益的生长反应。
确定预处理测试是否能识别对LUM - 201有反应的、具有足够残余功能的受试者的预测性富集标志物（PEM）。
我们对一项已完成的、随机、安慰剂对照的LUM - 201（一种GH促分泌剂受体激动剂）试验进行了分析，所有随机分组的受试者都进行了预处理测试。这项在儿科内分泌诊所开展的国际多中心研究纳入了68名初治的青春期前确诊为GHD的儿童。观察指标包括预测口服LUM - 201和每日重组人生长激素（rhGH）6个月生长反应的潜在标志物的敏感性、特异性和预测准确性。
确定了两个用于定义PEM阳性状态的PEM：（1）基线胰岛素样生长因子I（IGF - I）浓度>30 ng/mL，以及（2）单剂量LUM - 201给药后生长激素峰值反应≥5 ng/mL。PEM阳性状态使人群对LUM - 201有更好的生长反应。PEM阴性状态使人群对rhGH有更好的生长反应。
对于患有GHD的青春期前儿童，单剂量LUM - 201的生长激素峰值反应和基线IGF - I浓度相结合，是预测对LUM - 201和rhGH 6个月生长反应的有效PEM。
