A Study of GensSci098 in Subjects With Active Thyroid Eye Disease

Phase 1

Not yet recruiting

• Conditions: GenSci098; Safety; Tolerability; Thyroid Eye Disease (TED)

• Registration Number: NCT06569758
• Lead Sponsor: Changchun GeneScience Pharmaceutical Co., Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-8-14
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Not yet recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Inclusion Criteria:<br><br> 1. At the time of signing the informed consent form (ICF): aged between 18 and 75 years<br> (inclusive).<br><br> 2. Diagnosed by the physician as having active TED associated with Graves' disease<br> (GD), based on clinical and laboratory test results, with a CAS = 3 (on the 7-point<br> scale) for the most severely affected eye at screening and baseline.<br><br> 3. Onset of active symptoms and signs of TED (including one or more of the following:<br> conjunctival injection, conjunctival edema, eyelid hyperemia, eyelid edema, caruncle<br> swelling, spontaneous retrobulbar pain, and pain when trying to gaze up or down)<br> within 12 months prior to the screening visit.<br><br> 4. Positive for thyroid stimulating hormone receptor antibodies (TRAb) at screening.<br><br> 5. Moderate to severe TED (impacting the quality of life, requiring intervention but<br> not threatening vision), usually with at least 2 of the following manifestations:<br> (1) eyelid retraction width = 2 mm, (2) moderate or severe soft tissue involvement,<br> (3) proptosis = 3 mm above normal for race and gender, (4) inconstant or constant<br> diplopia.<br><br> 6. Participants must be euthyroid with the underlying disease under control, or have<br> mild hypo- or hyperthyroidism (defined as FT4 and FT3 levels below or above 50% of<br> the normal limits) at screening. (Only applicable to Part 1)<br><br> 7. Participants must have normal thyroid function or hyperthyroidism due to GD at<br> screening. (Only applicable to Part 2)<br><br> 8. No prior treatment with antithyroid medications, or having taken antithyroid<br> medications on a stable dose for at least 6 weeks, or having not been treated with<br> antithyroid medications due to intolerable side effects for at least 6 weeks. (Only<br> applicable to Part 2)<br><br> 9. Anyone who will not be required to need or receive any immediate or planned surgical<br> ophthalmological intervention, corrective surgery or orbital irradiation during the<br> study.<br><br> 10. Female participants must meet one of the following conditions to be eligible for the<br> study:<br><br> 1. Infertile, defined as surgical sterilization (hysterectomy, bilateral<br> salpingectomy, bilateral tubal ligation, or bilateral oophorectomy) at least 6<br> weeks prior to administration or menopausal (spontaneous amenorrhea = 12 months<br> which is not caused by underlying diseases and confirmed by serum follicle<br> stimulating hormone [FSH] level = 40 mIU/mL).<br><br> 2. Fertile female participants agree, from the start of the screening visit until<br> 24 weeks after the last dose, to consistently and correctly use one of the<br> following acceptable methods of effective contraception:<br><br> 1. Complete abstinence (based on the participant's preference and usual<br> lifestyle).<br><br> 2. Use of oral contraceptives (estrogen and progesterone), and being on a<br> stable dose of the same contraceptive medication for at least 3 months<br> prior to study treatment.<br><br> 3. Injectable or implantable hormonal contraception, or placement of an<br> intrauterine device (IUD) or intrauterine system (IUS), or other forms of<br> hormonal contraception with similar efficacy (failure rate < 1%), such as<br> a hormonal vaginal ring or transdermal hormonal contraception. 4)<br> Vasectomized partner, with the procedure performed at least 6 months ago.<br><br> 11. Male participants must meet one of the following criteria to be eligible for the<br> study:<br><br> 1) agree to use a condom plus an effective method of contraception (i.e., hormonal<br> contraception initiated at least 30 days prior to administration; or placement of an<br> IUD or IUS) when engaging in sexual activity with a female partner of childbearing<br> potential from the start of the screening visit until 24 weeks after the last dose<br> and refrain from donating sperm during this period.<br><br> 2) agree to practice abstinence from the start of the screening visit until 24 weeks<br> after the last dose.<br><br> 3) have had a vasectomy at least 6 months prior to study treatment. 12. Voluntarily<br> sign the ICF and be able to understand and comply with the study's treatment regimen<br> and assessments until the end of the study<br><br>Exclusion Criteria:<br><br> 1. Decreased best corrected visual acuity due to optic neuropathy as defined by a<br> decrease in vision of 2 or more lines on the Snellen chart or standard logarithmic<br> chart, new visual field defect, or color defect secondary to optic nerve involvement<br> within the last 6 months.<br><br> 2. Corneal injury not relieved by medical management.<br><br> 3. Improvement in CAS of = 2 points within 1 month prior to screening or between<br> screening and baseline.<br><br> 4. Decrease in proptosis of = 2 mm within 1 month prior to screening or between<br> screening and baseline.<br><br> 5. Previous orbital irradiation or surgery for TED.<br><br> 6. Use of any steroid (either intravenous or oral) with a cumulative dose equivalent to<br> = 1 g of methylprednisolone for TED within 4 weeks prior to screening (discontinued<br> steroid eye drops arepermitted).<br><br> 7. Use of steroids for conditions other than TED within 4 weeks prior to screening<br> (topical steroids for dermatological conditions and inhaled steroids are permitted).<br><br> 8. Drug therapy with biologics or peptides, including teprotumumab, rituximab, or<br> tocilizumab, within 6 months or 5 half-lives of the drug (whichever is longer) prior<br> to screening.<br><br> 9. Use of any non-steroidal immunosuppressive agents within the 3 months prior to<br> screening.<br><br> 10. Pre-existing ophthalmic disease or autoimmune disease (other than TED) that, in the<br> judgment of the investigator, would preclude study participation or complicate<br> interpretation of study results.<br><br> 11. History of hyperthyroidism not caused by GD (e.g., toxic adenoma or toxic<br> multinodular goiter), and/or current or previous history of thyroid storm. (Only<br> applicable to Part 2)<br><br> 12. History of radioiodine treatment or thyroidectomy. (Only applicable to Part 2)<br><br> 13. Individuals who cannot abstain from smoking/tobacco products from the screening<br> period to the end of the study.<br><br> 14. Any known allergy to the components of the investigational product or analogues or<br> previous allergic reactions to monoclonal antibodies.<br><br> 15. Known history /diagnosis of malignancy.<br><br> 16. Acute/chronic infection within 2 weeks prior to screening.<br><br> 17. Participation in another clinical trial within 3 months before screening (except<br> those who did not receive any intervention), or within 5 half-lives of the study<br> drug in other clinical trials (whichever is longer), or concurrent enrollment in<br> another clinical trial.<br><br> 18. Those with prolonged QTcF interval in 12-lead ECG results (> 450 ms for males, > 460<br> ms for females) or clinically significant abnormalities in other 12-lead ECG<br> parameters at screening;<br><br> 19. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels > 3 times<br> the ULN, or total bilirubin (TBIL) or alkaline phosphatase (ALP) > 2 × ULN, blood<br> creatinine (Cr) = 1.5 times the ULN at screening.<br><br> 20. Positive blood pregnancy test, or lactating women at the time of screening.<br><br> 21. Positive for hepatitis C virus antibody (

Exclusion Criteria

Not provided

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Incidence and severity of adverse events (AEs) (physical examination, vital signs, laboratory tests, 12-lead electrocardiogram [ECG]).

Secondary Outcome Measures

Name	Time	Method
PK parameters after single and multiple subcutaneous doses of GenSci098: maximum concentration at steady state (Cmax,ss);;PK parameters after single and multiple subcutaneous doses of GenSci098: minimum concentration at steady state (Cmin,ss);;PK parameters after single and multiple subcutaneous doses of GenSci098: time to maximum concentration at steady state (Tmax,ss);;PK parameters after single and multiple subcutaneous doses of GenSci098: average concentration at steady state (Cav,ss);;PK parameters after single and multiple subcutaneous doses of GenSci098: area under the concentration-time curve at steady state (AUC0-t,ss);;PK parameters after single and multiple subcutaneous doses of GenSci098: apparent clearance CL/F;PK parameters after single and multiple subcutaneous doses of GenSci098: half life t1/2,;Incidences of anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs), and titer of ADA.