Treatment of Active Thyroid Eye Disease With MHB018A in a Randomized, Placebo-Controlled Study

A Phase III, Randomized, Double-Masked, Placebo-Controlled Study to Evaluate the Efficacy of MHB018A Injection Treatment in Subjects With Active Moderate to Severe Thyroid Eye Disease.

The primary objective of this study is to evaluate the efficacy of MHB018A injection compared with placebo in participants with active moderate-to-severe TED.

The investigational drug, MHB018A, is a monoclonal antibody that inhibits the activity of a cell surface receptor called insulin-like growth factor-1 receptor (IGF-1R). Inhibition of IGF-1R may help to reduce the inflammation and associated tissue swelling that occurs in patients with thyroid eye disease (TED). The primary objective of this study is to evaluate the efficacy of MHB018A injection compared with placebo in participants with active moderate-to-severe TED.

Inclusion Criteria:

1. Subjects voluntarily participating in the study and signing the informed consent form;
2. Aged 18-75 years (inclusive), of any gender;
3. Clinical diagnosis of active Thyriod Eye Disease (TED). The Clinical Activity Score (CAS) of the study eye/target eye at screening and baseline must be ≥3 points (7-point scale).
4. Subjects with a clinical diagnosis of moderate to severe TED at screening and baseline.
5. Does not require immediate surgical ophthalmological intervention, and no corrective surgery/orbital radiotherapy is planned during the study.
6. Diabetic subjects must have well-controlled stable disease.
7. Sufficient bone marrow and organ function.
8. Eligible subjects of childbearing potential (male and female) must agree to use reliable contraceptive methods; female subjects of childbearing potential must have a negative blood pregnancy test within 7 days before the first use of the study drug and must not be breastfeeding.
9. Subject is willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the study.

Exclusion Criteria:

1. Decreased best corrected visual acuity due to optic neuropathy as defined by a decrease in vision within the last 6 months of two lines of Snellen chart, new visual field defect or color defect secondary to optic nerve involvement.
2. Corneal decompensation unresponsive to medical management.
3. Decrease in CAS of ≥ 2 points or decrease in proptosis of ≥ 2 mm between screening and baseline.
4. Free thyroxine (FT4) and free triiodothyronine (FT3) levels <50% above or below the normal reference range at screening.
5. Subjects who have previously received orbital radiotherapy or ophthalmic surgery for TED.
6. Subjects who received oral or intravenous corticosteroids or corticosteroid eye drops/ointments for TED within 4 weeks before the first dose; subjects who received periorbital/orbital steroid injections within 3 months before the first dose.
7. Subjects who used oral or intravenous corticosteroids for reasons other than TED within 4 weeks prior to Screening, excluding local use (topical, nasal, inhalation).
8. Any previous treatment with rituximab, tocilizumab, other immunosuppressive agent use within 3 months prior to Screening.
9. Previous treatment targeting IGF-1R.
10. Selenium and biotin must be discontinued 3 weeks prior to Screening and must not be restarted during the trial; however, taking a multivitamin that includes selenium and/or biotin is allowed.
11. Use of an investigational agent for any condition within 30 days prior to Screening or anticipated use during the course of the trial.
12. Identified pre-existing ophthalmic disease that, in the judgment of the Investigator, would preclude study participation or complicate interpretation of study results.
13. Malignant condition in the past 5 years before signing the ICF (except successfully treated basal/squamous cell carcinoma of the skin).
14. Acute cardiovascular disease history or treatment within 6 months before the first dose.
15. Presence of poorly controlled hypertension with systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg; Renal artery stenosis.
16. Pregnant or lactating women.
17. Drug or alcohol abuse during the screening period.
18. Hearing impairment history in either ear during the screening period; or abnormal pure tone audiometry results.
19. Biopsy-proven or clinically suspected inflammatory bowel disease.
20. Positive results for serum virology tests (defined as pos
21. Subjects who received or planned to receive live or attenuated live vaccines within 4 weeks before the first dose or during the study period.
22. Subjects who underwent major surgery within 4 weeks before the first dose or are expected to undergo surgery during the study period or within 4 weeks after the study.
23. Known hypersensitivity to any of the components of MNB018A or prior hypersensitivity reactions to mAbs.