The purpose of this study is to investigate the superiority of KPS-0373 to placebo, and evaluate the safety and pharmacokinetics of KPS-0373 in SCD patients.

开始日期2013-10-09

申办/合作机构

Kissei Pharmaceutical Co., Ltd.

NCT01970111 / Completed临床3期

An Extension Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)

The purpose of this study is to evaluate the long-term safety, efficacy, and pharmacokinetics of KPS-0373 in SCD patients.

开始日期-

申办/合作机构

Kissei Pharmaceutical Co., Ltd.

100 项与 Rovatirelin Hydrate 相关的临床结果

登录后查看更多信息

100 项与 Rovatirelin Hydrate 相关的转化医学

登录后查看更多信息

100 项与 Rovatirelin Hydrate 相关的专利（医药）

登录后查看更多信息

1,255

项与 Rovatirelin Hydrate 相关的文献（医药）

2024-03-01·Clinical endocrinology

Anaemia‐based screening for resistance to thyroid hormone alpha in children

Article

作者: Demir, Korcan ; Abacı, Ayhan ; Kağızmanlı, Gözde Akın ; Kırbıyık, Özgür ; Yiş, Uluç ; Böber, Ece

Abstract:

Background:

The hypothyroid phenotype associated with resistance to thyroid hormone alpha (RTH‐α) is associated with a diverse clinical picture. On the other hand, thyroid‐stimulating hormone (TSH) levels are normal. Free triiodothyronine (fT3) and free thyroxine (fT4) levels can also be normal; however, normo‐ or macrocytic anaemia is usually present in reported cases. Diagnosis is challenging and there is limited data regarding screening methods.

Objective:

The study aimed to assess the efficiency of a screening strategy for RTH‐α.

Subjects and Methods:

Out of a total of 6540 children evaluated at the outpatient clinics of paediatric neurology over 2 years and who underwent complete blood count and thyroid function tests, 432 were found to have anaemia. Within this group, we identified 42 children without an underlying specific neurological aetiology who exhibited normo‐ or macrocytic anaemia, normal TSH levels, fT3 levels in the upper half of the normal range or high, and fT4 levels in the lower half of the normal range or low. We excluded one patient who had already been diagnosed with RTH‐α and nine patients could not be reached. Subsequently, clinical evaluation, biochemical assessment, and THRA sequencing analysis were conducted on 32 children. The findings were compared with those of the known RTH‐α patients in our unit.

Results:

The median age of the patients was 5.7 (5.1–7.4) years, and 22 of them were males (69%). The main reasons for assessment in paediatric neurology clinics were autism spectrum disorder (n = 12, 38%), epilepsy (n = 11, 34%), and delay in developmental stages (n = 8, 25%). Constipation was present in five of the cases (16%), while the closure of the anterior fontanelle and tooth eruption were delayed in two cases (6%) and one case (3%), respectively. The median length/height and weight standard deviation (SD) scores were 0.3 [(−0.8)–(1.1)] and −0.1 [(−0.8)–(0.3)], respectively. The median fT3, fT4, and TSH levels were 4.6 (4.2–5.0) pg/mL, 0.9 (0.8–1.0) ng/dL, and 2.2 (1.8–3.1) uIU/mL, respectively. Thirteen of the patients (41%) had high fT3 levels, while none of them had low fT4 levels. The normo‐ or macrocytic anaemia rate was 47% (normocytic/macrocytic, n = 8/7) at the time of reassessment. Serum creatine kinase (CK) was elevated in five patients (16%; one had anaemia). None of the subjects had a pathological variant in THRA. Known RTH‐α patients had significantly lower median height SD score, higher rates of delayed tooth eruption and closure of the anterior fontanelle, lower haemoglobin levels, and higher mean corpuscular volume (MCV) and CK levels as compared to those found without RTH‐α.

Conclusions:

This approach found one known patient with RTH‐α but did not reveal any new cases. Notably, normo‐ or macrocytic anaemia did not persist in nearly half of the screened patients. A screening strategy that takes clinical findings and prominent laboratory features suggestive of RTH‐α into account could lower unnecessary genetic analysis of THRA in patients presenting with neurological problems.

2024-02-20·The Journal of clinical endocrinology and metabolism

TSH and FT4 Reference Interval Recommendations and Prevalence of Gestational Thyroid Dysfunction: Quantification of Current Diagnostic Approaches

Article

作者: Taylor, Peter N ; Grineva, Elena N ; Korevaar, Tim I M ; Walsh, John P ; Vasukova, Elena A ; Brown, Suzanne J ; Tao, Fang-Biao ; Lu, Xuemian ; Chatzi, Lida ; Popova, Polina V ; Vafeiadi, Marina ; Nicolaides, Kypros H ; Huang, Kun ; Ashoor, Ghalia ; Derakhshan, Arash ; Sitoris, Georgiana ; Aminorroaya, Ashraf ; Bliddal, Sofie ; Poppe, Kris G ; Suvanto, Eila ; Palomaki, Glenn E ; Osinga, Joris A J ; López-Bermejo, Abel ; Chen, Liangmiao ; Männistö, Tuija ; Pop, Victor J M ; Bassols, Judit ; D'Alton, Mary E ; Hattersley, Andrew ; Feldt-Rasmussen, Ulla ; Chaker, Layal ; Vaidya, Bijay ; Nelson, Scott M ; Kianpour, Maryam ; Broeren, Maarten A C ; Vrijkotte, Tanja G M

Abstract:

Context:

Guidelines recommend use of population- and trimester-specific thyroid-stimulating hormone (TSH) and free thyroxine (FT4) reference intervals (RIs) in pregnancy. Since these are often unavailable, clinicians frequently rely on alternative diagnostic strategies. We sought to quantify the diagnostic consequences of current recommendations.

Methods:

We included cohorts participating in the Consortium on Thyroid and Pregnancy. Different approaches were used to define RIs: a TSH fixed upper limit of 4.0 mU/L (fixed limit approach), a fixed subtraction from the upper limit for TSH of 0.5 mU/L (subtraction approach) and using nonpregnancy RIs. Outcome measures were sensitivity and false discovery rate (FDR) of women for whom levothyroxine treatment was indicated and those for whom treatment would be considered according to international guidelines.

Results:

The study population comprised 52 496 participants from 18 cohorts. Compared with the use of trimester-specific RIs, alternative approaches had a low sensitivity (0.63-0.82) and high FDR (0.11-0.35) to detect women with a treatment indication or consideration. Sensitivity and FDR to detect a treatment indication in the first trimester were similar between the fixed limit, subtraction, and nonpregnancy approach (0.77-0.11 vs 0.74-0.16 vs 0.60-0.11). The diagnostic performance to detect overt hypothyroidism, isolated hypothyroxinemia, and (sub)clinical hyperthyroidism mainly varied between FT4 RI approaches, while the diagnostic performance to detect subclinical hypothyroidism varied between the applied TSH RI approaches.

Conclusion:

Alternative approaches to define RIs for TSH and FT4 in pregnancy result in considerable overdiagnosis and underdiagnosis compared with population- and trimester-specific RIs. Additional strategies need to be explored to optimize identification of thyroid dysfunction during pregnancy.

2024-01-01·Annals of surgical treatment and research

Effect of thyroid-stimulating hormone suppression on quality of life in thyroid lobectomy patients: interim analysis of a multicenter, randomized controlled trial in low- to intermediate-risk thyroid cancer patients (MASTER study)

Article

作者: Kim, Woochul ; Kim, Hee Kyung ; Lee, Ja Kyung ; Kim, Mijin ; Kang, Yea Eun ; Choi, June Young ; Ryu, Junsun ; Ku, Eu Jeong ; Jung, Kyong Yeun ; Cho, Jae Won ; Yu, Hyeong Won ; Kim, Su-Jin

Purpose:

Current clinical practices favor less or no thyroid-stimulating hormone (TSH) suppression for low- to intermediate-risk thyroid cancer patients who receive thyroid lobectomy. The association of TSH suppression on health-related quality of life (HR-QoL) in patients after thyroid lobectomy is not well studied. This study aimed to evaluate the effect of TSH suppression on patient HR-QoL after thyroid lobectomy.

Methods:

This study included patients enrolled in an ongoing, multicenter, randomized controlled study investigating the effects of TSH suppression. Patients were randomized to either the low-TSH group (TSH target range, 0.3-1.99 µIU/mL) or the high-TSH group (TSH target range, 2.0-7.99 µIU/mL). The HR-QoL, hyperthyroidism symptom, and depression symptom questionnaires performed preoperatively and 2 weeks and 3 months postoperatively were evaluated.

Results:

Total of 669 patients (low-TSH group, 340; high-TSH group, 329) were included. Although total HR-QoL score changes were not different between the 2 groups, the high-TSH group had a significantly higher score in the physical domain at postoperative 3 months (P = 0.046). The 2 groups did not have significant differences in hyperthyroidism and depression scores.

Conclusion:

In the short-term postoperative period, the physical HR-QoL scores in thyroid lobectomy patients were better when they did not receive TSH suppression. This study suggests the importance of considering HR-QoL when setting TSH suppression targets in thyroid lobectomy patients.

项与 Rovatirelin Hydrate 相关的新闻（医药）

2023-09-26

·CPHI制药在线

新药 | 泽璟制药重组人促甲状腺激素3期临床达主要终点，国内还有谁在布局?

关注并星标CPHI制药在线近日，泽璟制药宣布其研发的注射用重组人促甲状腺激素（rhTSH）用于分化型甲状腺癌患者术后辅助诊断的3期临床试验ZGTSH004达到了方案预设的主要终点。 ZGTSH004研究是一项开放、单臂、自身对照、多中心的3期临床研究，在中国医学科学院北京协和医院、河南省肿瘤医院等研究中心开展，这项临床试验主要目的是评价分化型甲状腺癌术后辅助诊断131I全身显像（WBS）中，使用rhTSH处理的显像效果不劣于甲状腺激素撤除疗法（THW）。结果显示，该研究有效性和安全性结果符合预期，达到方案预设的主要终点。泽璟制药将向中国国家药品监督管理局药品审评中心（CDE）提交生物新药上市申请（Pre-BLA）的沟通交流申请，推进注射用重组人促甲状腺激素的上市进程。 rhTSH的临床应用与市场潜力据全国肿瘤登记中心的数据显示，我国每年新发甲状腺癌病人约 22 万人，并以每年 20% 的速度持续增长。分化型甲状腺癌（DTC) 占所有甲状腺癌病例数的 95% 以上。根据Frost & Sullivan分析，近年来，由于早期诊断手段的进步和筛查加强，分化型甲状腺癌新发病例数快速增加，由2016年的19.2万人增长到了2020年的21.0万人。根据Frost & Sullivan的预测，到2030年，分化型甲状腺癌的新发病例数会增长至26.0万人。促甲状腺激素（TSH）是糖蛋白激素家族成员，其能够增加碘以及放射碘的摄取和有机化，从而杀伤甲状腺癌细胞。与此同时，TSH 的激活也可以导致甲状腺细胞释放甲状腺球蛋白（Tg）、三碘甲状腺原氨酸（T3）和甲状腺素（T4），其中 Tg 作为血液中甲状腺癌的肿瘤标志物，被用于检测甲状腺癌。重组人促甲状腺素（rhTSH）是基于生物技术生产的化合物，其在分子结构及作用方面与天然促甲状腺激素（TSH）相同。手术切除+TSH 抑制治疗+131I 治疗是目前国际公认的分化型甲状腺癌治疗的金标准。131I 治疗或随访复查前，均需要将病人血清 TSH 水平升高至 30mU/L 以上。提升 TSH 的方法有 2 种：一是传统的甲状腺激素撤退（THW），即停服甲状腺素 3-4 周，以提高内源性 TSH 的分泌；二是给予外源性 TSH，即肌肉注射 rhTSH。国内外多个指南强力推荐使用 rhTSH 作为停用甲状腺素的取代疗法，如《欧洲甲状腺学会（ETA）共识（2022 版）》、中国肿瘤临床诊疗指南《甲状腺癌诊疗指南 (2022 版)》等。图片来源：智碘化蝶与 THW 方式相比，使用 rhTSH能够安全、快速提升血清 TSH 水平，仅需 1-2 天即可达到治疗要求，缩短治疗等待时间，还能够满足特殊患者的需求：即使停服甲状腺素后，体内 TSH 水平仍达不到治疗要求的患者。此外，选择 rhTSH 方式不需要停服甲状腺素，不会引起甲状腺功能减退如体重增加、畏寒、抑郁等不适症状，提高患者生活质量，最大程度的降低疾病复发的风险。 1998年，Genzyme公司研发的重组人促甲状腺素α（rhTSH）药物Thyrogen在美国上市，先后获批用于分化型甲状腺癌术后的辅助治疗和随访中用作血清甲状腺球蛋白（Tg）测试的辅助诊断工具。 Thyrogen可安全、快速提升人体血清促甲状腺素水平，避免了停服甲状腺激素产生的不良反应，因此，被诸多相关的临床指南推荐作为碘131治疗前与随访复查检测中停服甲状腺激素时的替代疗法。但上市20多年，已进入全球共72个国家和地区的Thyrogen，曾在中国大陆地区递交多次IND申请，最终都因各种原因以失败告终。而中国每年新发甲状腺癌20余万人，大陆地区至今无任何一个rhTSH药物上市，市场完全空白，医生与患者均无药可用。根据 Frost & Sullivan 的预测，由于国内甲状腺癌患者数量的逐年增加，相关 rhTSH 市场将由 2023 年的 1.6 亿元增长到 2030 年的 14.1 亿元。 rhTSH：智核生物与泽璟制药两强争霸虽然rhTSH在临床上存在巨大的市场需求，但其作为糖蛋白类药物，其开发工艺复杂、研发难度大、技术壁垒高，目前在国内还无同类上市产品。公开资料显示，国内仅智核生物和泽璟制药两个玩家在布局，原研药Thyrogen由于生产工艺问题，在中国大陆地区难以上市，这也成为国内玩家弯道超车的机会。智核生物重组人促甲状腺素注射液（SNA001) 的生物制品许可申请（BLA）已于2022年7月获 CDE 受理，拟用于无远处转移分化型甲状腺癌患者在甲状腺全切或近全切术后碘 [131I] 清除残余甲状腺组织的治疗。最新审评进度显示，SNA001已进入补充资料任务第一轮，最快有望于今年获批上市。图片来源：CDE官网而此次泽璟制药达到3期临床终点的是：重组人促甲状腺激素（rhTSH）对比停服甲状腺激素疗法用于分化型甲状腺癌患者术后辅助诊断"。两家公司拟申请的适应症并不一致，智核生物申报的rhTSH应用于治疗，而泽璟即将提交上市申请的rhTSH应用于诊断，形成了差异化竞争。期待国内rhTSH尽快上市，满足甲状腺癌治疗和诊断的临床需求，为我国广大的甲状腺癌患者带来全新选择。参考来源： 1. Hofmann MC, et al. Molecular mechanisms of resistance to kinase inhibitors and redifferentiation in thyroid cancers. Endocr Relat Cancer. 2022 Sep 14;29(11):R173-R190. 2. Haugen BR, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016 Jan;26(1):1-133. 3. 各企业官网 4. CDE官网来源：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~

临床结果临床3期

100 项与 Rovatirelin Hydrate 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D10594	-	-	DB15338

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
脊髓小脑性共济失调	申请上市	日本	Kissei Pharmaceutical Co., Ltd.	2021-12-22
脊髓小脑变性	临床3期	日本	Kissei Pharmaceutical Co., Ltd.	2013-10-09
半规管裂综合征	临床2期	日本	Kissei Pharmaceutical Co., Ltd.	2009-03-18
帕金森病	临床前	日本	Shionogi & Co., Ltd.	-

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02889302 \| NCT01970098 (Pubmed \| J Neurol Neurosurg Psychiatry)	临床3期	小脑共济失调	-	rovatirelin 2.4 mg	(顧鬱窪蓋醖齋淵蓋願鹹): adjusted mean change = -0.61 (95% CI, -1.16 ~ -0.06), P-Value = 0.029	-	2020-03-01
				placebo