This is a single-center, prospective, randomized, controlled (crossover) clinical study designed to investigate the specific dose-response impact of insulin infusion rate (IIR) on blood glucose levels during a pancreatic clamp study. The investigators will recruit participants with a history of overweight/obesity and evidence of insulin resistance (i.e., fasting hyperinsulinemia plus prediabetes and/or impaired fasting glucose and/or Homeostasis Model Assessment of Insulin Resistance [HOMA-IR] score >=2.73), and with evidence of, or clinically judged to be at high risk for, uncomplicated non-alcoholic fatty liver disease (NAFLD). Participants will undergo two pancreatic clamp procedures in which individualized basal IIR are identified, followed in one by maintenance of basal IIR (maintenance hyperinsulinemia, MH) and in the other by a stepped decline in IIR (reduction toward euinsulinemia, RE). In both clamps the investigators will closely monitor plasma glucose and various metabolic parameters. The primary outcome will be the absolute and relative changes in steady-state plasma glucose levels at each stepped decline in IIR.

开始日期2023-08-29

申办/合作机构

Columbia University

[+2]

NCT00757393 / Completed临床3期IIT

Growth Hormone Therapy and Bone Quality in Pediatric Osteoporosis

The primary objective of this study is to test the hypothesis that growth hormone, administered daily by subcutaneous injection for 2 years will result in a significantly greater BMD Z-score over optimal standard therapy.

开始日期2008-09-01

申办/合作机构

The Hospital for Sick Children

NCT00355030 / Completed临床3期

Efficacy and Safety of Somatropin in Combination With Leuprorelin Compared to Somatropin Alone in Pubertal Children With Idiopathic Short Stature

The present randomized trial was initially intended to study the benefits of a combined treatment with growth hormone (GH) and a gonadotropin-releasing hormone (GnRH) agonist for pubertal children with idiopathic short stature. However, treatments were stopped in January 2012 at the request of the French drug agency. Therefore, a protocol amendment divided the study in two study periods.
Study Period 1 involved combined treatment with somatropin and leuprorelin or treatment with somatropin alone. Participants from France who participated in this Period 1 of the study were asked to participate in a long term safety follow up defined as a Period 2 of the study. Participants from the Netherlands were offered participation in Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS, clinicaltrials.gov Identifier: NCT01088412) for long term safety follow up independent of this study.

开始日期2006-06-01

申办/合作机构

Eli Lilly & Co.

100 项与生长激素(Eli Lilly & Co.) 相关的临床结果

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项与生长激素(Eli Lilly & Co.) 相关的文献（医药）

2022-08-12·Cureus

Attenuation of Human Growth Hormone-Induced Rash With Graded Dose Challenge

作者: Lozeau, Daniel ; Luo, Evelyn ; Donovan, Daniel ; Rizvi, Khizer ; Agrawal, Nidhi ; Gunther, Regina ; Caruana, Dennis ; Hessel, Justina ; Mann, Jake ; Khanijo, Sameer ; Lee-Wong, Mary ; Chan, Derek ; Neumann, Melissa ; Hasan, Zubair ; Gottesman, Eric ; Szema, Anthony M

Adult growth hormone (GH) deficiency is rare and requires replacement with extrinsic/synthetic injection. GH hypersensitivity has been reported; specifically, atopic patients may develop rashes from somatotropin therapy. Allergic and non-allergic skin reactions to recombinant human GH are uncommon and infrequently reported. We describe a graded-dose challenge with intravenous Norditropin® in a 65-year-old atopic adult woman who developed a severe whole-body rash with Norditropin FlexPro® administration on several occasions but was negative on skin-prick testing to Norditropin® percutaneously and intradermally, but the patch testing was positive for gold and nickel. The patient was registered as a direct admission to the emergency room at a university hospital for a rapid antigen coronavirus disease 2019 (COVID-19) testing after having received two COVID-19 vaccinations and re-testing four months after vaccination. She was then directly admitted to a non-COVID-19 intensive care unit with direct bedside supervision by a registered nurse and a physician board certified in internal medicine, allergy/immunology, and pulmonary diseases. The patient brought a Norditropin® pen which our pharmacy team attached to a compatible syringe for dilutions. A graded dose challenge at a final dosage of 0.1 mL was performed and the patient was monitored for allergic and other adverse drug reactions, which did not occur. At the time of writing this case report, the patient has been maintained on Norditropin FlexPro® 0.1 mL and has not experienced any adverse reactions, including recurrent skin eruptions. The case presented is the first to describe a patient who successfully tolerated a graded dose challenge of an adult patient to GH replacement therapy (as Norditropin®) under supervision in an intensive care unit, whereas prior to reporting of this case, a graded dose challenge to GH replacement therapy had only been successfully performed in a child using another formulation of somatotropin (Humatrope®). Hence, this case lends support that graded dose challenge with somatotropin analogs may be considered for patients with isolated GH deficiency such as in the case presented here.

2017-01-01·Clinical Pediatric Endocrinology

Incidence of diabetes mellitus and neoplasia in Japanese short-statured children treated with growth hormone in the Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS)

Article

作者: Hasegawa, Tomonobu ; Yokoya, Susumu ; Child, Christopher J. ; Jia, Nan ; Funai, Jumpei ; Tanaka, Toshiaki ; Ozono, Keiichi ; Chihara, Kazuo ; Iwamoto, Noriyuki ; Kanzaki, Susumu ; Tanaka, Hiroyuki ; Ihara, Katsuichiro ; Seino, Yoshiki

The primary goal of the Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS) was to assess the safety and effectiveness of Humatrope^®, a GH preparation, in the treatment of pediatric patients with short stature. We report our findings in the GH-treated Japanese pediatric population focusing on the incidence of type 2 diabetes (T2D) and occurrence of neoplasms. A total of 2,345 Japanese patients were assessed for safety. During a mean observation period of 3.2 yr, T2D occurred in 3 patients (0.13%) and slowly progressive insulin-dependent diabetes mellitus (SPIDDM) related to underlying mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) in 1 patient (0.04%). Neoplasms were reported in 13 patients (0.56%), including 1 patient with brain tumor (germinoma) and 5 with craniopharyngiomas (4 recurrences); the remainder were benign, typically dermatological, neoplasms. The incidence of diabetes mellitus determined in the study did not differ from previous reports in GH-treated pediatric patients, and there was no apparent increase in the risk of new neoplastic lesions or malignant tumors.

2013-01-01·Endocrine journal4区 · 医学

An observational study of the effectiveness and safety of growth hormone (Humatrope<sup>®</sup>) treatment in Japanese children with growth hormone deficiency or Turner syndrome

4区 · 医学

Article

作者: Seino, Yoshiki ; Hasegawa, Tomonobu ; Tai, Shigeru ; Fujieda, Kenji ; Tanaka, Toshiaki ; Ozono, Keichi ; Kanzaki, Susumu ; Chihara, Kazuo ; Yokoya, Susumu ; Tanaka, Hiroyuki

This study assessed the effectiveness and safety of growth hormone (GH; Humatrope(®)) therapy in Japanese children with GH deficiency (GHD) or Turner syndrome (TS) enrolled in the Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS). GeNeSIS is an open-label, multinational, multicenter, observational study conducted in 30 countries. In this interim report, there were 1129 GH treatment-naïve children with GHD, with a mean chronological age (± standard deviation) of 8.75 (3.32) years, and 90 girls with TS, with a mean chronological age of 8.93 (3.67) years. The mean height standard deviation score (SDS) increased from -2.73 (0.63) SD and -2.71 (0.63) SD at study entry to -2.22 (0.68) SD and -2.20 (0.60) SD after 1 year of treatment in the GHD and TS groups, respectively. In both groups, mean height SDS increased further with each year of treatment to 4 years; however, the magnitude of change in height SDS declined with time. The mean insulin-like growth factor-I SDS increased from below the mean of the reference population at study entry to a level similar to (GHD group) or higher than (TS group) the mean of the reference population during the 4-year treatment period. The incidence of serious adverse events (AEs), treatment-related AEs, and AEs related to glucose intolerance was low in both groups (0.1% to 3.0%). In conclusion, GH treatment in Japanese children with GHD or TS resulted in increased growth over a 4-year treatment period with a favorable safety profile; however, the improvements in growth declined with time.

项与生长激素(Eli Lilly & Co.) 相关的新闻（医药）

2024-03-13

·CPHI制药在线

增高药竞争白热化：周制剂前途可期，口服疗法进展顺利

关注并星标CPHI制药在线3月8日，维昇药业（VISEN Pharmaceuticals）宣布中国国家药品监督管理局（NMPA）已受理隆培促生长素（lonapegsomatropin，Skytrofa）的上市许可申请（BLA）。隆培促生长素是第一个在欧美获批上市的长效生长激素，每周注射一次，用于治疗儿童生长激素缺乏症。隆培促生长素是采用全球极具创新性的TransConTM（Transient Conjugation, 暂时连接）专利技术平台设计的人生长激素前药，能够以可控的方式在体内缓慢释放未经修饰的生长激素，血浆半衰期可达30.7（±12.7）小时，支持每周一次给药。已公布的隆培促生长素针对中国生长激素缺乏症（GHD）儿童患者的3期临床试验数据显示：治疗52周时，隆培促生长素治疗组儿童生长激素缺乏症患者的年化生长速率（AHV）显著高于生长激素日制剂组（10.66厘米/年Vs 9.75厘米/年），达到研究主要终点。此外，在52周治疗期间，隆培促生长素治疗组和生长激素日制剂组患者的平均胰岛素样生长因子-1（IGF -1）标准差积分(SDS)均增加至正常范围内，且隆培促生长素组相对较高。IGF -1是肝脏对生长激素反应时产生的一种多肽，可刺激软骨细胞增殖、分化和胶原的合成。而且，隆培促生长素耐受性良好，安全性与生长激素日制剂相当。隆培促生长素由Ascendis Pharma开发，维昇药业拥有其在大中华区的独家开发、制造和商业化权益。2021年8月，该药被FDA用于治疗年龄在一岁及以上、体重至少11.5公斤、因内源性生长激素分泌不足而导致生长迟缓的儿童患者。2022年1月，该药在欧盟被批准用于治疗因内源性生长激素分泌不足而导致的3-18岁儿童和青少年生长迟缓。据公司财报，隆培促生长素2022年、2023年销售额分别为35百万欧元和179百万欧元，预计2024年将达到320-340百万欧元。生长激素药物的发展迭代生长激素缺乏症（GHD），又称垂体性侏儒，因下丘脑-垂体轴的器质性病变或是功能性异常导致生长激素缺乏引起，患者不仅表现为身材矮小，还存在代谢异常、心理社会挑战、认知缺陷和生活质量差等问题。据公开资料，我国儿童患矮小症的比例约为3%，其中GHD最为常见，占比约三分之一。补充生长激素是目前公认治疗儿童GHD最有效方法之一。生长激素是人脑垂体前叶嗜酸性细胞分泌的一种长度为191个氨基酸的肽类激素，通过刺激肝脏等组织产生胰岛素样生长因子（IGF -1）发挥生理功能，促进骨骼生长，促进蛋白质合成，调节脂肪、糖、矿物质代谢等，在人体生长发育过程中发挥重要作用。根据制备技术的迭代，生长激素药物的研发经历了五代更替。其中第一代生长激素从人脑垂体中提取，存在来源受限、传递传染性疾病的风险，且会引起慢性脑部海绵样变性导致死亡，世界各国已相继停用。第二代生长激素是利用大肠杆菌包涵体技术合成的基因重组人生长激素（rhGH），与天然生长激素结构不同，由192个氨基酸组成，但容易产生抗体影响疗效，目前已淘汰。第三代生长激素是利用普通大肠杆菌以及哺乳动物真核表达系统，表达合成的含有191个氨基酸的 rhGH ，结构与hGH还有差异，存在易产生抗体、成本高和易污染等缺点。第四代生长激素是利用哺乳动物细胞重组DNA技术合成的含有191个氨基酸的生长激素，其结构和天然的生长激素结构更为接近，目前仅被极少数生产厂家沿用。第五代生长激素是利用分泌型大肠杆菌表达技术合成，其氨基酸含量、序列和蛋白质结构与人垂体生长激素完全一致，因此生物活性高、免疫原性低、副作用少。剂型上，目前市面上的生长激素产品包括短效粉针、短效水针和长效水针，其中粉针粉针和短效水针在疗效上没有显著差异，但针粉临床使用繁琐，注射前需抽取抑菌水注入冻干粉容器中重新配制，不过其稳定性较水针好。金赛药业领跑，国内多款生长激素产品获批上市目前，国内已批准多款生长激素产品，详见下表。整体来看，国内生长激素持有企业比较集中，主要为金赛药业、安科生物等。其中金赛药业是国内生长激素的领军企业，且是国内唯一实现短效粉针、短效水针、长效水针三种剂型全部上市的企业。据米内网数据，2022年中国城市公立医院、县级公立医院、城市社区中心以及乡镇卫生院（简称中国公立医疗机构）终端生长激素销售规模约为67亿元，其中金赛药业是行业老大，市场占比超80%：在粉针剂市场，金赛药业市场份额占比超50%；在水针剂市场，金赛药业市场份额高达99%；金赛增是国内唯一获批的长效水针，2022年销售额超7亿元。对比国外，国内批准的长效生长激素水针有限，仅金赛药业的金赛增。目前，国外已批准多款长效生长激素水针，即Ascendis Pharma的Skytrofa、诺和诺德的Sogroya和辉瑞的Ngenla。上述四款长效生长激素的长效作用机制还不太一样。其中Skytrofa是凭借TransCon技术，该技术可使其给药后以可控方式在一周内缓慢释放未经修饰的活性生长激素，从而发挥作用。Sogroya是一种hGH的长效类似物，由天然的hGH经过修饰以增强其与血浆白蛋白的结合，使其适合每周一次给药。Ngenla也是一种长效hGH类似物，利用OPKO专有的C末端肽段（CTP）长效技术在一段天然生长激素序列的C和N末端分别加上了2个和1个来自人类绒毛膜促性腺激素（HCG）β亚基的CTP拷贝，使其半衰期得以延长。金赛增是全球首支上市的聚乙二醇（PEG）化长效生长激素注射液，其利用天然肽键连接了惰性PEG和天然结构的生长激素，从而降低其被肾脏过滤的速度和蛋白酶对它的降解作用，进而提高其在人体内的稳定性。此外，微球技术也被开发用长效生长激素领域，如基因泰克的Nutropin Depot、韩国LG Life Sciences的 Declage。其中Nutropin Depot是全球第一个上市的长效生长激素，其采用PLGA缓释微球技术，缓释效果显著，1999年获批上市，但后续因注射局部疼痛，4年后退市。Declage采用的是透明质酸技术，2007年在韩国上市。长效生长激素有哪些后备军长效生长激素是儿童GHD生长激素替代疗法研发的热门方向，目前全球药企已研发出多款在研长效生长激素，详见下表。我国药企也积极布局长效生长激素，其中特宝生物的怡培生长激素已于今年1月在国内报产。怡培生长激素由特宝生物自主研发，其采用40kD Y型分支聚乙二醇（YPEG）分子对rhGH进行单分子修饰，优选高生物学活性、非N-末端位点为主的修饰组分，在保证疗效的同时，旨在降低给药剂量，获得更佳的长期药物安全性。已公布的2/3期研究数据显示：儿童GHD患者接受12周治疗后，怡培生长激素100、120、140μg/kg/周组和重组人生长激素35μg/kg/天组（对照组）的身高增长速度分别为7.07、10.39、12.27厘米/年和11.58厘米/年。天境生物的伊坦生长激素进展也相对较快，其治疗儿童GHD的3期研究已达到非劣效性主要终点，今年将递交上市申请。该药是基于Genexine的专利hyFc®技术开发，hyFc部分由人免疫球蛋白D（IgD）和G4（IgG4）的一部分组成。前者包含一个柔性铰链，后者可通过新生儿Fc受体（FcRn）介导的代谢调控延长半衰期。已公布的3期临床试验结果显示：伊坦生长激素组患者的年化身高生长速率（AHV）为10.76厘米/年，而Norditropin（诺泽）组患者的AHV为10.28厘米/年。值得一提的是，围绕伊坦生长激素药企间达成数项交易。该药由Genexine开发，2015年10月天士力子公司Tasgen（被天境生物收购）与Genexine达成协议，获得伊坦生长激素的中国权益。2021年11月，天境生物将伊坦生长激素的商业化权益授权给济川药业。安科生物、优诺金的长效生长激素处于2期临床，其中AK2017通过采用Fc融合蛋白结合技术延长半衰期，是重组人GH同源二聚体与通过突变的人IgG4-Fc的融合蛋白。此外，除了皮下注射生长激素，儿童GHD患者还有望迎来口服疗法。2023年11月，Lumos Pharma生长激素促分泌素受体（GHSR）激动剂LUM-201治疗儿童GHD的两项2期研究（OraGrowtH210研究和OraGrowtH212研究）达到了所有主要终点及次要终点。总结生长激素药物的问世给儿童生长激素缺乏症（GHD）患者带来了希望。历经60多年的发展，生长激素药物的研发取得巨大成功，已从每日一次给药实现每周一次给药的跨越。全球儿童GHD的治疗规模也随之扩大，Frost & Sullivan数据显示其2030年有望达到60亿美元。目前，我国也已批准多款生长激素药物，但长效制剂相对国外较少，而且生长激素药物的市场渗透率也比较低。不过随着生长激素纳入集采，我国将有更多的儿童GHD患者接受生长激素治疗。期待未来有更多的新型生长激素药物获批上市，造福众多儿童GHD患者。参考资料： 1.《生长激素行业深度：长效剂型快速放量，产品出海未来可期》.青山医药笔记.2024-02-07 2.《洞察o创新｜慎思而笃行：生长激素发展历程带来的挑战与风险》.全球健康产业创新观察.2023-07-20 3.《临床需求决定研发方向：生长激素的不断进步史》.医学界儿科频道.2022-10-14 【智药研习社近期直播预告】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

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外链

KEGG	Wiki	ATC	Drug Bank
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研发状态

适应症	最高研发状态	国家/地区	公司
垂体性侏儒症	批准上市	日本更多	Eli Lilly Japan KK 更多
侏儒症	批准上市	美国更多	Eli Lilly & Co. 更多
特发性矮小症	批准上市	美国更多	Eli Lilly & Co. 更多
生长激素缺乏症	批准上市	日本更多	Eli Lilly Japan KK 更多
成长不全	无进展	美国更多	Eli Lilly & Co. 更多

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00001305 (CTgov)	临床3期	成骨不全症IV型 \| 生长激素缺乏症	42	Humatrope	醖獵願鬱鹹襯壓鑰顧廠(鹹網願襯餘鏇淵糧積膚) = 窪淵憲鏇獵鹽網憲艱網齋醖艱積觸艱衊繭鑰積 (鏇蓋遞範憲淵鏇鏇憲繭, 淵憲齋艱糧觸遞膚憲窪 ~ 積觸醖選糧襯鏇獵觸簾) 更多	-	2019-01-29
NCT00355030 (CTgov)	临床3期	特发性矮小症	91	Somatropin+Leuprorelin (Somatropin and Leuprorelin)	願願鑰齋淵憲構餘醖繭(繭簾鬱製窪糧餘繭夢鏇) = 壓壓淵獵獵觸積範齋蓋顧餘鹽糧鹽範簾築鏇簾 (繭鬱鏇構鹽繭衊憲壓蓋, 構網繭範膚遞壓簾選觸 ~ 壓餘觸壓構艱鏇遞衊壓) 更多	-	2016-10-18
				somatropin (Somatropin)	願願鑰齋淵憲構餘醖繭(繭簾鬱製窪糧餘繭夢鏇) = 窪餘顧網鬱鹽遞顧齋衊顧餘鹽糧鹽範簾築鏇簾 (繭鬱鏇構鹽繭衊憲壓蓋, 鬱襯鏇鹽醖廠艱壓積糧 ~ 蓋網築鹽夢範願製範築) 更多
NCT00266656 (CTgov)	临床4期	特纳综合症	69	GDFG+Humatrope (Early Treated)	鬱窪網醖顧膚糧齋壓襯(遞壓憲醖製築鏇製製齋) = 獵蓋蓋觸築壓觸廠餘艱鏇淵選鬱齋觸製鑰積廠 (餘簾簾糧廠蓋壓製醖觸, 襯築鬱餘糧築願醖範網 ~ 選襯築鹽遞觸壓壓糧憲) 更多	-	2016-08-23
				B9R+Humatrope (Early Untreated)	鬱窪網醖顧膚糧齋壓襯(遞壓憲醖製築鏇製製齋) = 積夢繭網襯憲鏇衊廠構鏇淵選鬱齋觸製鑰積廠 (餘簾簾糧廠蓋壓製醖觸, 製壓餘築觸襯網糧衊顧 ~ 築艱製簾膚鏇鏇構衊夢) 更多
NCT00191165 (CTgov)	临床3期	生长激素缺乏症	27	Somatropin (High Dose Somatropin)	遞觸窪憲壓選鏇淵餘鑰(鑰顧廠鑰壓築鏇壓鏇艱) = 壓廠網願憲衊襯範觸衊鏇壓範蓋範鹹糧願艱襯 (獵衊餘獵範願糧築積醖, 餘願壓鑰憲醖膚衊製襯 ~ 築齋衊觸夢窪觸衊簾鑰) 更多	-	2009-06-08
				Somatropin (Label Dose Somatropin)	遞觸窪憲壓選鏇淵餘鑰(鑰顧廠鑰壓築鏇壓鏇艱) = 鏇膚襯範齋廠積衊範窪鏇壓範蓋範鹹糧願艱襯 (獵衊餘獵範願糧築積醖, 餘繭鏇窪範顧憲鏇製願 ~ 憲鏇鹽憲積齋選淵範鬱) 更多