Clinical Trial of Dose-tolerance, Pharmacokinetics and Iodine Uptake For rhTSH In Post-thyroidectomized Patients

Study Overview
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Brief Summary
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Phase I/II Clinical Trial of Dose-tolerance, Pharmacokinetics and Iodine Uptake Effects For Recombinant Human Thyroid Stimulating Hormone In Post-thyroidectomized Patients

Detailed Description
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This phase I/II study of rhTSH, To observe the safety and tolerability characteristics of different doses of rhTSH In Post-thyroidectomized Patients, and to observe the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD).

Official Title
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Phase I/II Clinical Trial of Dose-tolerance, Pharmacokinetics and Iodine Uptake For Recombinant Human Thyroid Stimulating Hormone In Post-thyroidectomized Patients

Conditions
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Differentiated Thyroid Cancer

Intervention / Treatment
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* Drug: Recombinant Human Thyroid Stimulating Hormone for Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathological diagnosis of differentiated thyroid cancer, including papillary thyroid cancer (including papillary carcinoma follicular subtype), follicular thyroid cancer, and Hurthle cell thyroid cancer; Screening ages 18-75 (including 18 Age and 75 years old, male or female; Weight 45kg-80kg (including 45kg and 80kg, limited to the dose escalation test); Complete thyroidectomy or near total resection, and plan to start 131I diagnosis or ablation Patients Serum TSH ≤ 0.5 mU/L; Women of childbearing age are HCG-negative and must continue contraception until more than 3 months after the end of the trial; Subjects (including partners) from 2 weeks prior to dosing to the last study drug There is no pregnancy plan within 3 months after the drug and voluntary effective contraceptive measures are taken. For specific contraceptive measures, see Appendix 3; Normal ECG. Intermittent atrial premature beats, supraventricular tachycardia (SVT) or supraventricular block-independent PR interval abnormalities, right bundle branch block, mild sinus bradycardia (asymptomatic, and no treatment required) Can be grouped; Low iodine diet before enrollment for more than 4 weeks; Patients are voluntarily enrolled, and written informed consent forms can be used for treatment and visits as required by the program. Exclusion Criteria: Patients who are not eligible for THST withdrawal due to pituitary disease or other diseases; Patients not eligible for 131I diagnosis or treatment; Any significant clinical and laboratory abnormalities (eg, severe cardiopulmonary disease, hepatic insufficiency, renal function) Incomplete, congestive heart failure, advanced lung disease or advanced cardiovascular and cerebrovascular disease, active infection); Hypertensive patients who cannot be reduced to the following range due to medical treatment (systolic blood pressure <140 mmHg, diastolic blood pressure <90 mmHg); Patients who have used any water-soluble radiographic contrast agent intravenously within 4 weeks before administration; Patients who underwent intrathecal iodine angiography or gallbladder iodine imaging within 3 months prior to administration; taken/eaten within 4 weeks prior to administration Drugs/foods that affect iodine uptake or metabolism, such as multivitamins, glucocorticoids, diuretics, lithium, thiouracil, tazobactam, algae, iodine (except thyroid hormone replacement therapy); before administration Stroke, unstable angina (CCS class II or higher), atrial fibrillation or medication (within beta blocker or digoxin) within 6 months Patients with a history of arrhythmia; pregnant or lactating women; a history of drug use and/or alcohol abuse within 3 months prior to dosing; patients who are allergic to rhTSH and its excipients; patients with positive infection-related tests : Includes hepatitis C and AIDS; Participated in any drug or medical device clinical trial within 1 month prior to the trial; Those who were unable to participate in the trial as judged by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rhTSH<br>Phase 1: 0.9mgx1d、0.9mgx2d、1.8mgx1d、1.8mgx2d, intramuscularly (IM) ; Phase 2: patients will be treated at the recommended dose for phase 2(RP2D).The RP2D will be determined by the Phase 1. | Drug: Recombinant Human Thyroid Stimulating Hormone for Injection<br>* rhTSH was dissolved in 1.2 mL of sterile water for injection to obtain a solution containing 0.9 mg/mL rhTSH.<br>* Other names: rhTSH;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTD | the maximum tolerathed dose | up to 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | maximum serum thyrotropin concentrations | up to 5 days | 
| AUC | area under curve of serum thyrotropin concentration | up to 5 days | 
| Serum Tg | serum Tg levels | up to 7 days | 
| radioiodine uptake | whole body radioiodine imaging after rhTSH administration and after thyroid hormone withdrawal | up to 8 weeks | 
| adverse event | classification and degree of adverse events | up to 8 weeks |