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Evaluation of SNA001, a Novel Recombinant Human Thyroid Stimulating Hormone Injection, in Patients With Differentiated Thyroid Carcinoma

SNA001 is a novel recombinant human thyroid stimulating hormone (rhTSH). rhTSH has long been approved in several countries to facilitate monitoring and ablation of thyroid carcinoma without hypothyroidism caused by thyroid hormone withdrawal (THW). To assess the safety, tolerance, pharmacokinetic an...

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Autores principales: Gu, Yushen, Xu, Hongrong, Yang, Yanling, Xiu, Yan, Hu, Pengcheng, Liu, Min, Wang, Xiangqing, Song, Jun, Di, Yan, Wang, Jian, Zhang, Xiaoxia, Xu, Tao, Li, Xuening, Shi, Hongcheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927955/
https://www.ncbi.nlm.nih.gov/pubmed/33679603
http://dx.doi.org/10.3389/fendo.2020.615883
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author Gu, Yushen
Xu, Hongrong
Yang, Yanling
Xiu, Yan
Hu, Pengcheng
Liu, Min
Wang, Xiangqing
Song, Jun
Di, Yan
Wang, Jian
Zhang, Xiaoxia
Xu, Tao
Li, Xuening
Shi, Hongcheng
author_facet Gu, Yushen
Xu, Hongrong
Yang, Yanling
Xiu, Yan
Hu, Pengcheng
Liu, Min
Wang, Xiangqing
Song, Jun
Di, Yan
Wang, Jian
Zhang, Xiaoxia
Xu, Tao
Li, Xuening
Shi, Hongcheng
author_sort Gu, Yushen
collection PubMed
description SNA001 is a novel recombinant human thyroid stimulating hormone (rhTSH). rhTSH has long been approved in several countries to facilitate monitoring and ablation of thyroid carcinoma without hypothyroidism caused by thyroid hormone withdrawal (THW). To assess the safety, tolerance, pharmacokinetic and pharmacodynamic properties of SNA001, the two-period (SNA001 period and THW period), dose-ascending study in well-differentiated thyroid cancer (DTC) patients was designed. Three doses (0.45 mg, 0.9 mg, and 1.35 mg) of SNA001 were intramuscularly injected, twice in the SNA001 period to stimulate iodine-131 uptake and thyroglobulin (Tg) release. 24 h after the last dose of SNA001, iodine-131 (111–185 MBq) was administrated, followed by whole-body scan (WBS) 48 h later. THW period began just after SNA001 washout and lasted for about 3–6 weeks. When TSH level was above 30 mU/L, iodine-131 (111–185 MBq) was administrated, followed by a WBS and Tg detection 48 h later. Twenty-four DTC patients after thyroidectomy were enrolled; mean peak concentrations of SNA001 in 0.45, 0.9, and 1.35 mg groups were 18.5, 26.7, and 37.0 ng/ml (about 244.7, 354.2, and 489.6 mU/L) respectively, within 28–32 h after first dose of SNA001. SNA001 was metabolized in a dose-dependent manner. The results of WBS and Tg release in the SNA001 period were compared with those in the THW period. Compared to Tg level in baseline, the Tg levels in SNA001 and THW periods were increased, with 78% of subjects showing higher Tg levels in the THW period. 100% of the patients had concordant qualitative results of the scans within two periods in three groups. Symptoms of hypothyroidism were relieved in the SNA001 period compared with THW period, though there was no significant difference in most of the scale scores. There were no serious adverse events related to SNA001; the most common adverse events were gastrointestinal symptoms of mild and transient nature. Thus, SNA001 promises to be a safe and effective method to stimulate iodine-131 uptake and Tg secretion during monitoring and ablation for DTC without the disadvantages of incidental hypothyroidism.
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spelling pubmed-79279552021-03-04 Evaluation of SNA001, a Novel Recombinant Human Thyroid Stimulating Hormone Injection, in Patients With Differentiated Thyroid Carcinoma Gu, Yushen Xu, Hongrong Yang, Yanling Xiu, Yan Hu, Pengcheng Liu, Min Wang, Xiangqing Song, Jun Di, Yan Wang, Jian Zhang, Xiaoxia Xu, Tao Li, Xuening Shi, Hongcheng Front Endocrinol (Lausanne) Endocrinology SNA001 is a novel recombinant human thyroid stimulating hormone (rhTSH). rhTSH has long been approved in several countries to facilitate monitoring and ablation of thyroid carcinoma without hypothyroidism caused by thyroid hormone withdrawal (THW). To assess the safety, tolerance, pharmacokinetic and pharmacodynamic properties of SNA001, the two-period (SNA001 period and THW period), dose-ascending study in well-differentiated thyroid cancer (DTC) patients was designed. Three doses (0.45 mg, 0.9 mg, and 1.35 mg) of SNA001 were intramuscularly injected, twice in the SNA001 period to stimulate iodine-131 uptake and thyroglobulin (Tg) release. 24 h after the last dose of SNA001, iodine-131 (111–185 MBq) was administrated, followed by whole-body scan (WBS) 48 h later. THW period began just after SNA001 washout and lasted for about 3–6 weeks. When TSH level was above 30 mU/L, iodine-131 (111–185 MBq) was administrated, followed by a WBS and Tg detection 48 h later. Twenty-four DTC patients after thyroidectomy were enrolled; mean peak concentrations of SNA001 in 0.45, 0.9, and 1.35 mg groups were 18.5, 26.7, and 37.0 ng/ml (about 244.7, 354.2, and 489.6 mU/L) respectively, within 28–32 h after first dose of SNA001. SNA001 was metabolized in a dose-dependent manner. The results of WBS and Tg release in the SNA001 period were compared with those in the THW period. Compared to Tg level in baseline, the Tg levels in SNA001 and THW periods were increased, with 78% of subjects showing higher Tg levels in the THW period. 100% of the patients had concordant qualitative results of the scans within two periods in three groups. Symptoms of hypothyroidism were relieved in the SNA001 period compared with THW period, though there was no significant difference in most of the scale scores. There were no serious adverse events related to SNA001; the most common adverse events were gastrointestinal symptoms of mild and transient nature. Thus, SNA001 promises to be a safe and effective method to stimulate iodine-131 uptake and Tg secretion during monitoring and ablation for DTC without the disadvantages of incidental hypothyroidism. Frontiers Media S.A. 2021-02-17 /pmc/articles/PMC7927955/ /pubmed/33679603 http://dx.doi.org/10.3389/fendo.2020.615883 Text en Copyright © 2021 Gu, Xu, Yang, Xiu, Hu, Liu, Wang, Song, Di, Wang, Zhang, Xu, Li and Shi http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Gu, Yushen
Xu, Hongrong
Yang, Yanling
Xiu, Yan
Hu, Pengcheng
Liu, Min
Wang, Xiangqing
Song, Jun
Di, Yan
Wang, Jian
Zhang, Xiaoxia
Xu, Tao
Li, Xuening
Shi, Hongcheng
Evaluation of SNA001, a Novel Recombinant Human Thyroid Stimulating Hormone Injection, in Patients With Differentiated Thyroid Carcinoma
title Evaluation of SNA001, a Novel Recombinant Human Thyroid Stimulating Hormone Injection, in Patients With Differentiated Thyroid Carcinoma
title_full Evaluation of SNA001, a Novel Recombinant Human Thyroid Stimulating Hormone Injection, in Patients With Differentiated Thyroid Carcinoma
title_fullStr Evaluation of SNA001, a Novel Recombinant Human Thyroid Stimulating Hormone Injection, in Patients With Differentiated Thyroid Carcinoma
title_full_unstemmed Evaluation of SNA001, a Novel Recombinant Human Thyroid Stimulating Hormone Injection, in Patients With Differentiated Thyroid Carcinoma
title_short Evaluation of SNA001, a Novel Recombinant Human Thyroid Stimulating Hormone Injection, in Patients With Differentiated Thyroid Carcinoma
title_sort evaluation of sna001, a novel recombinant human thyroid stimulating hormone injection, in patients with differentiated thyroid carcinoma
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927955/
https://www.ncbi.nlm.nih.gov/pubmed/33679603
http://dx.doi.org/10.3389/fendo.2020.615883
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