Diffuse toxic goiter
Conditions
Interventions
Cohort 1 (90 mg):GenSci098 90 mg, single subcutaneous injection
Cohort 2 (180 mg):GenSci098 180 mg, single subcutaneous injection
Cohort 3 (270 mg):GenSci098 270 mg, single subcutaneous injection
Sponsors
The First Affiliated Hospital of China Medical University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Signed informed consent form (ICF); age = 18 years. 2. Previously or at screening diagnosed with Graves' disease (GD) by a physician based on clinical and laboratory findings (provide examination reports and medical records). 3. Screening laboratory results meet the following criteria: FT4 > 1.5 × ULN and = 5 × ULN; TSH < LLN; TRAb positive (based on the upper limit of normal at the study center). 4. Patients who have never received antithyroid drugs (ATDs), or those who previously received ATDs but have discontinued treatment for = 4 weeks prior to screening. 5. Female subjects must meet one of the following conditions to participate: (1) Not of childbearing potential, defined as having undergone surgical sterilization (hysterectomy, bilateral salpingectomy, bilateral tubal ligation, or bilateral oophorectomy) at least 6 weeks before dosing, or being postmenopausal (spontaneous amenorrhea for = 12 months not caused by underlying disease, with serum follicle-stimulating hormone [FSH] = 40 mIU/mL); (2) Of childbearing potential, and agree to consistently use one of the following acceptable effective contraceptive methods from the screening visit until 140 days after the last dose: 1) Complete abstinence (based on the subject's preference and usual lifestyle); 2) Condoms combined with the rhythm method; 3) Oral contraceptives (estrogen and progestin), with stable use of the same contraceptive medication for at least 3 months prior to receiving study treatment; 4) Injectable or implantable hormonal contraception, intrauterine device (IUD), or intrauterine system (IUS), or other forms of hormonal contraception with similar efficacy (failure rate < 1%), such as hormonal vaginal rings or transdermal hormonal contraceptives; 5) Their male partner underwent surgical sterilization at least 6 months ago. 6. Male subjects must meet one of the following conditions to participate: (1) Agree to use effective contraceptive measures (such as condoms combined with the rhythm method, or hormonal contraception started at least 30 days before dosing, or IUD/IUS) when engaging in sexual activity with female partners of childbearing potential from the screening visit until 140 days after the last dose, and refrain from donating sperm during this period; (2) Agree to complete abstinence from the screening visit until 140 days after the last dose; (3) Underwent surgical sterilization at least 6 months before study treatment. 7. Voluntarily sign the ICF, able to understand and comply with the study protocol and assessments, and attend regular follow-up visits on schedule.
Exclusion criteria
Exclusion criteria: 1. History of hyperthyroidism caused by non-Graves' disease (e.g., toxic multinodular goiter or toxic thyroid adenoma). 2. Previous treatment with radioactive iodine (RAI) or thyroid surgery (fine-needle aspiration biopsy of the thyroid is permitted). 3. History of thyroid storm, and/or currently assessed by the investigator as having related risks. 4. Use of any dose of levothyroxine (L-T4), desiccated thyroid extract, or liothyronine within 4 weeks prior to screening. 5. Patients with active Thyroid Eye Disease (TED), defined as Clinical Activity Score (CAS) = 3, severe soft tissue involvement (defined as at least one of conjunctival injection or eyelid swelling being severe in the CAS score), or intermittent/persistent diplopia. 6. Previous orbital radiotherapy or surgery for TED, or requiring immediate surgical or medical intervention for TED, and/or planning radiotherapy, surgery, or medical treatment for TED during the study. 7. Evidence of optic neuropathy and/or corneal damage. 8. Use of glucocorticoids (intravenous, oral, or intraorbital injection) or immunosuppressants within 3 months prior to screening, or biologics within 6 months prior to screening. 9. Unable to stop smoking/use tobacco products from screening until the end of the study. 10. Known allergy to any component of the investigational drug or its analogs, or previous allergic reaction to monoclonal antibodies. 11. Participation in other clinical trials within 3 months prior to screening (except for those who received no interventions), or within 5 half-lives of other investigational drugs (whichever is longer), or currently participating in other clinical trials. 12. Screening 12-lead ECG showing QTcF interval prolongation (male > 450 ms, female > 460 ms), or other clinically significant abnormalities in 12-lead ECG parameters. 13. Screening alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 × upper limit of normal (ULN), or total bilirubin (TBIL) > 2 × ULN, or serum creatinine (Cr) = 1.5 × ULN. 14. Female subjects who are pregnant or breastfeeding at screening, or have a positive blood pregnancy test at screening. 15. Positive human immunodeficiency virus antibody (HIV Ab) or Treponema pallidum particle agglutination assay (TPPA) at screening; positive hepatitis C virus antibody (HCV Ab) at screening; positive hepatitis B surface antigen (HBsAg) at screening, or currently receiving anti-hepatitis B virus treatment. 16. History of drug addiction or abuse, or positive urine drug screen at screening. 17. Concurrent other autoimmune diseases requiring treatment, assessed by the investigator as unsuitable for participation in the study. 18. Known or confirmed history of malignancy. 19. History of splenectomy; major surgery within 6 months prior to screening or planned major surgery in the near future. 20. Suffering from or having a history of other serious infectious, cardiovascular, respiratory, hepatobiliary, renal, endocrine, digestive, hematological, or neurological diseases, assessed by the investigator as potentially posing safety risks. 21. Presence of other clinically significant laboratory abnormalities, or other reasons deemed by the investigator as unsuitable for participation in this clinical study (such as any medical or other conditions that may affect the clinical trial).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The incidence and severity of adverse events (AE), physical examination, vital signs, laboratory tests, 12-lead electrocardiogram, etc.; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic parameters of GenSci098 after single subcutaneous administration: AUC0-t, AUC0-8, Cmax, Tmax, t1/2, CL/F, Vd/F, etc.;Incidence and titers of anti-drug antibodies (ADA);Incidence of neutralizing antibodies (NAb);Changes in serum thyroid function panel (TSH, FT3, FT4, TT3, rT3, TT4);Changes in TSH receptor antibody (TRAb) and thyroid-stimulating antibody (TSAAb);Globe proptosis (CAS);Diplopia (CAS);Quality of life in ophthalmic disease (GO-QoL); | — |
Countries
China
Contacts
Public ContactShan Zhongyan
The First Affiliated Hospital of China Medical University
Outcome results
None listed