Abstract
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.
Highlights
Thyroid carcinoma had an estimated incidence of 567,233 new cases and 41,071 deaths in 2018, worldwide
We report the pharmacokinetics, pharmacodynamics, safety, and tolerance of SNA001, the first Recombinant human thyrotropin stimulating hormone (rhTSH) analog to be available in China, in patients with differentiated thyroid carcinoma
ThyrogenTM is on the market in 72 countries or regions [11]
Summary
Thyroid carcinoma had an estimated incidence of 567,233 new cases and 41,071 deaths in 2018, worldwide. In China, the estimated incidence in 2015 was 90,000 cases with approximately 6,800 deaths [1,2,3]. Both estimates show that, despite the high incidence, thyroid carcinoma has high survival rates. Around 30% of patients relapse, with two-thirds of the recurrences occurring within the first decade after therapy. Near-total, thyroidectomy followed by iodine-131 adjuvant and L-thyroxine therapy and regular follow-up approach are adopted, nearly 90% of the patients remain permanently free of the disease [5]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
