A Phase Ib/II, Efficacy and Safety Study of NTB003 in Participants With Thyroid Eye Disease (TED)
A Phase Ib/II, Efficacy and Safety Study of NTB003 in Participants With Thyroid Eye Disease (TED)
Multicentre, Phase Ib/II Clinical Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of NTB003 in Participants with Thyroid Eye Disease
Inclusion Criteria:
1. Male or female subjects aged 18-75 years who have signed informed consent. 2.Body weight between 40 kg and 100 kg. 3.Clinical diagnosis of thyroid eye disease (TED): Active thyroid eye disease (TED): at least one eye with a CAS ≥ 3 and proptosis ≥ 3 mm above the upper limit of normal in that eye, and the subject's first onset of TED ocular signs/symptoms (by subject report or medical records) occurred within 1 year prior to first study drug administration; Chronic Thyroid Eye Disease (TED) : bilateral CAS < 3, and the first onset of TED ocular signs/symptoms (by subject report or medical records) occurred > 12 months prior to first study drug administration.
4.Subjects clinically graded as having moderate-to-severe TED per the European Group on Graves' Orbitopathy (EUGOGO) classification at screening and baseline, typically accompanied by proptosis ≥ 3 mm above the upper limit of normal (normal range 12-16 mm). In addition, subjects should have one or more of the following features: eyelid retraction ≥ 2 mm, moderate or severe soft-tissue involvement, or intermittent/persistent diplopia.
5.Do not require immediate ophthalmic surgical intervention and no corrective surgery or orbital radiotherapy is planned during the study.
6.Euthyroid with underlying thyroid disease controlled, or mild hypothyroidism or hyperthyroidism (defined as screening free triiodothyronine [FT3] and free thyroxine [FT4] levels < 50% above or below the normal limits).
7.Subjects of childbearing potential must agree to use effective contraception during the trial and for at least 6 months after the last dose. Acceptable methods include complete abstinence, barrier contraception (e.g., condom), tubal ligation, intrauterine device, hormonal contraception (oral contraceptives, injections, transdermal patch, vaginal ring, or implant), or partner vasectomy.
8.Female subjects of childbearing potential must have a negative pregnancy test within 7 days prior to first study drug administration and must not be breastfeeding.
Exclusion Criteria:
1. A reduction of ≥2 points in the CAS value or a reduction of ≥2 mm in proptosis in the study eye from the screening assessment period to study baseline period.
2.Within 6 months prior to screening, decrease in best corrected visual acuity (BCVA) attributable to TED optic neuropathy, defined as a loss of two lines of acuity, new visual field defect, or color vision defect secondary to optic nerve involvement.
3.Corneal abnormalities that, in the investigator's opinion, could affect efficacy assessments.
4.Prior or planned orbital radiotherapy or ocular surgery for TED, including orbital decompression, strabismus surgery, eyelid surgery, or similar procedures.
5.History of clinically significant hearing impairment, or abnormal pure-tone audiometry at screening.
6.History of inflammatory bowel disease, or clinically suspected inflammatory bowel disease (e.g., unexplained diarrhea with or without blood or rectal bleeding plus abdominal pain or cramping for >4 weeks; endoscopic or imaging evidence of enteritis/colitis without other explanation).
7.Prior treatment with IGF-1 or IGF-1R-related agents. 8.Poorly controlled diabetes at screening. 9.Poorly controlled hypertension at screening. 10.AST or ALT > 3×ULN; or serum creatinine > 1.5×ULN; or platelet count < 100 × 10^9/L; or neutrophil count < 2.0 × 10^9/L at screening:.
11.Active hepatitis, defined as HBsAg positive with detectable HBV DNA above the local laboratory's lower limit of detection; or HCV antibody positive.
12.History of HIV infection or positive HIV antibody test. 13.Any active or suspected bacterial, viral, or fungal infection (e.g., severe common cold, viral syndrome, influenza-like illness) requiring intravenous antimicrobial therapy within 4 weeks prior to first dose.
14.Receipt of, or planned receipt during the study of, live or live-attenuated vaccines within 4 weeks prior to first dose.
15.Use of selenium, biotin, or traditional Chinese medicine therapies for TED (e.g., triptolide-containing compounds, Epimedium, polygonum cuspidatum, lotus seed heart, acupuncture, etc.) within 3 weeks prior to first dose or planned use during the study; combination multivitamins containing selenium and/or vitamins are permitted.
16.Use of oral or intravenous systemic glucocorticoids for any reason within 4 weeks prior to first dose; or topical ophthalmic glucocorticoid eye drops/ointments for TED within 7 days prior to first dose. Use of topical glucocorticoids for non-TED indications (e.g., dermatologic conditions) before or during the study is allowed.
17.Use of oral or intravenous nonsteroidal immunosuppressants for TED (e.g., mycophenolate mofetil, cyclosporine, methotrexate, azathioprine, etc.) within 4 weeks prior to first dose; or topical ophthalmic nonsteroidal immunosuppressant eye drops for TED within 7 days prior to first dose.
18.Periocular/orbital steroid injection within 3 months prior to first dose. 19.Treatment with anti-CD20 antibodies, interleukin-6 antibodies, or other biologic agents for TED within 3 months prior to first dose.
20.Botulinum toxin (or other chemical denervation agents) treatment for TED within 3 months prior to first dose.
21.Participation in another interventional clinical trial within 3 months prior to first dose.
22.Known or suspected allergy to the investigational product or any of its components, or prior history of hypersensitivity to other antibody drugs.
23.Any prior or concomitant disease or condition that, in the investigator's judgment, may interfere with trial compliance or affect evaluation of trial results (e.g., psychiatric disorders, recent acute cardiovascular or cerebrovascular events, history of treated or untreated malignancy within 5 years), or any other condition deemed by the investigator to make the subject unsuitable for participation.