Study of ZB001 in Chinese Patients With Thyroid Eye Disease

A Multiple Ascending Doses Study of ZB001 in Chinese Patients With Thyroid-Associated Ophthalmopathy

The investigational drug, ZB001 is a humanized IgG1κ monoclonal antibody targeting human IGF-1R. The study is designed to evaluate the efficacy, safety, tolerability, and pharmacokinetics（PK）/pharmacodynamics (PD) profile of ZB001 in Chinese patients with Thyroid Eye Disease.

Inclusion Criteria:

1. Male or female adults, 18 years of age or older
2. Clinical diagnosis of Graves' ophthalmopathy and CAS evaluation of eyes under study ≥ 4 points (7 points in total)
3. Moderate-to-severe active thyroid-associated ophthalmopathy (i.e., severely affects daily life): exophthalmos extent is ≥18.6 mm, or progressive exophthalmos (≥3 mm greater than the previous exophthalmos record per the investigator); accompanied by at least one of the following symptoms: eyelid retraction ≥ 2 mm; moderate or severe soft tissue involvement (conjunctival congestion, edema, periorbital congestion or edema); non-persistent or persistent diplopia
4. Before Screening, evidence of eye symptoms or signs related to thyroid-associated ophthalmopathy in medical records for ≤1 year
5. Thyroid function normal, or only mild hyperthyroidism or hypothyroidism, defined as free thyroxine (FT4) ）and free triiodothyronine (FT3) levels within 0.5-1.5 times the normal range at Screening. Efforts have been made to correct any mild hypothyroidism or hyperthyroidism in a timely manner and try to maintain normal thyroid function throughout the study. Thyroidectomy is not an exclusion.
6. If the patient is a female of childbearing potential (including a female with menopause < 1 year, amenorrhea < 1 year, or without surgical sterilization), the pregnancy test result will be negative at Screening. Such patients must agree to use the effective birth control methods described in the relevant protocol section (Section 9.2 Contraception and Pregnancy) at least one complete menstrual cycle before the first dose of the study drug, and continue to use contraception methods for 100 days after the last dose
7. Male patients must be surgically sterilized for at least 6 weeks or agree to use the effective birth control methods described in the relevant protocol section (Section 9.2 Contraception and Pregnancy) before the first dose of the study drug and within 100 days after the last dose

Exclusion Criteria:

1. In the past 6 months, due to optic neuropathy, new visual field defect or color defect secondary to optic nerve involvement, the best corrected visual acuity of the study eye decreased, defined as the result of standardized visual acuity chart decreased ≥ 0.2
2. Corneal involvement of the study eye, and no improvement after medical interventions
3. CAS decreased ≥ 2 points from Screening Assessment to Day -1
4. The exophthalmos extent of the study eye ≥ 2 mm from Screening Assessment to Day -1
5. The study eye previously received orbital radiotherapy or surgery due to thyroid-associated ophthalmopathy
6. Known history of clinically significant ear disease, ear surgery or hearing loss
7. Inflammatory bowel disease (e.g., biopsy-proven or clinical evidence of inflammatory bowel disease)
8. Cumulative use of glucocorticoid equivalent to ≥ 1g methylprednisolone as thyroid-associated ophthalmopathy treatment (A lower cumulative dose [<1g] of glucocorticoid used before Screening, or hormone eye drops withdrawn for ≥ 6 weeks before Screening, is allowed for inclusion)
9. Received any doses of oral corticosteroids to treat diseases other than thyroid-associated ophthalmopathy within 4 weeks before Screening (local application is allowed for inclusion)
10. Pregnant or lactating females
11. Smokers (≥ 5 cigarettes/day) or former smokers (≥ 5 cigarettes/day) quit within 6 months before enrollment in the study
12. Any vaccination planned during the study