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This is a multicenter, randomized, double-masked, placebo-controlled Phase II/III study in subjects with active thyroid eye disease. Approximately 114 subjects meeting study eligibility criteria will be randomly assigned to IBI311 or placebo on day 1 (D1) in a 2:1 ratio stratified by smoking status
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Participants with TED will be randomized to receive 4 intravenous infusions of Placebo with an interval of 3 weeks for phase II and 8 intravenous infusions of Placebo with an interval of 3 weeks for phase III. |
|
| IBI311 | Active Comparator | Participants with TED will be randomized to receive 4/8 intravenous infusions of IBI311 with an interval of 3 weeks for phase II/III. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IBI311 | Biological | 10 mg/kg on Day 1 followed by 20 mg/kg q3W for the remaining 7 infusions for phase II/III. |
|
| Measure | Description | Time Frame |
|---|---|---|
| The proptosis responder rate of the study eye (defined as percentage of subjects with a ≥ 2mm reduction from Baseline in proptosis in the study eye, without deterioration [≥ 2 mm increase] of proptosis in the non-study eye). | proptosis assessment: amount of protrusion of the eye from the orbital rim measured by Hertel exophthalmometer | Week 12 for phase II, Week 24 for phase III |
| Measure | Description | Time Frame |
|---|---|---|
| The overall responder rate in the study eye. | Responder rate were defined as participants with a reduction in clinical activity score (CAS, see Secondary Outcome Measure 2 description for details) of ≥ 2 points, and a reduction in proptosis of ≥ 2 mm in the study eye, and no deterioration (increase in CAS of ≥ 2 points or increase in proptosis of ≥ 2 mm) in the non-study eye.) | Week12 and Week24 for phase II, Week 24 for phase III |
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Key Inclusion Criteria:
Key Exclusion Criteria:
Subjects will be ineligible for study participation if they meet any of the following criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine | Shanghai | Shanghai Municipality | 200000 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41066129 | Derived | Zhang H, Sun J, Li Y, Zhu L, Shan Z, Lu W, Shen J, Shi Y, Tao L, Jiang H, Ji L, Zhu Y, Gu H, Liu X, Sun B, Tian Y, Liu Q, Zhou J, Zhao H, Guan H, Zhu L, Wen J, Lu Y, Qiao J, Zhang W, Deng J, Lu S, Han-Zhang H, Qian L, Zhou H, Fan X. IGF-1R Inhibitor IBI311 for the Treatment of Active Thyroid Eye Disease in Chinese Patients: The RESTORE-1 Randomized Clinical Trial. JAMA Ophthalmol. 2025 Nov 1;143(11):964-971. doi: 10.1001/jamaophthalmol.2025.3350. |
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| ID | Term |
|---|---|
| D049970 | Graves Ophthalmopathy |
| ID | Term |
|---|---|
| D015785 | Eye Diseases, Hereditary |
| D005128 | Eye Diseases |
| D006111 | Graves Disease |
| D005094 | Exophthalmos |
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| placebo | Biological | 4 does of placebo for phase II; 8 does of placebo for phase III. |
|
| Percentage of subjects with a CAS value of 0 or 1 in the study eye. | According to the 7-item European Group on Graves' Ophthalmopathy (EUGOGO) amendment, CAS was used to evaluate clinical activity. For each of the following items, one point is given: spontaneous orbital pain, gaze evoked orbital pain, eyelid swelling that is considered to be due to active (inflammatory phase) Graves' ophthalmopathy (GO), eyelid erythema, conjunctival redness that is considered to be due to active (inflammatory phase) GO, chemosis, and inflammation of caruncle or plica. The sum of these points is the total score, with 0 indicating no clinical activity and 7 indicating the most severe clinical activity. | Week12 and Week24 for phase II, Week 24 for phase III |
| Mean Change of the CAS value in the study eye. | Baseline to Week 12 and Week 24 for phase II |
| Mean change from Baseline in proptosis measurement in the study eye. | proptosis measurement: see Primary Outcome Measure 1 description for details | Baseline to Week 12 and Week 24 for phase II, Baseline to Week 24 for phase III |
| The proptosis responder rate of the study eye. | proptosis responder rate: see Primary Outcome Measure 1 description for details | Week 24 for phase II |
| The diplopia responder rate of the study eye. | Week12 and Week24 for phase II, Week 24 for phase III |
| D009916 |
| Orbital Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D006042 | Goiter |
| D013959 | Thyroid Diseases |
| D004700 | Endocrine System Diseases |
| D006980 | Hyperthyroidism |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |