The Safety and Efficacy of Sequential Hormone Therapy and IBI311 Therapy in Patients With Active Moderate to Severe TAO in the Initial Treatment.

NCT ID: NCT07152340

Last Updated: 2025-09-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-10
• Study Completion Date: 2030-05-01

Brief Summary

Thyroid-associated ophthalmopathy (TAO) is an organ-specific autoimmune disease closely related to thyroid disease, which leads the incidence of orbital disease in adults and is the most common cause of diffuse toxic goiter (Graves disease, GD). The clinical manifestations of TAO are complex and varied. In severe cases, it may seriously impair visual function, affect daily life, and even cause corneal ulceration, perforation, and blindness. Therefore, a reasonable and effective treatment plan should be chosen according to the degree of TAO.

Tetuzumab (IBI311) is a fully human monoclonal insulin-like growth factor-1 receptor inhibitory antibody. It has binding activity against IGF-1R positive cells, can block the binding of IGF-1 and IGF-2 to IGF-1R, and has a dose-dependent effect. It can inhibit the proliferation of HT29 cells caused by the activation of the IGF-1R signaling pathway. Meanwhile, it can dose-dependently inhibit the proliferation of orbital fibroblasts and the secretion of hyaluronic acid (HA) in patients with TAO.

However, there are still significant gaps in the existing research evidence: the lack of head-to-head studies of temumab and glucocorticoids.

The aim of this clinical study is to:

1. To evaluate the efficacy of IBI311 treatment in patients with active moderate to severe TAO in the initial treatment.

2. To observe the safety of IBI311 treatment in patients with active moderate to severe TAO in the initial treatment.

3. Head-to-head comparison of sequential hormone therapy and IBI311 therapy in patients with active moderate to severe TAO in the initial treatment.

Conditions

Thyroid Associated Ophthalmopathies

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IBI311

8 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 7 infusions)

Group Type: ACTIVE_COMPARATOR

IBI311

Intervention Type: DRUG

IBI311 is a fully human anti-IGF-1R mAb. IBI311 will be provided in single-dose 10-mL glass vials as a Injection solution containing.

Glucocorticoid

Patients with active thyroid ophthalmopathy will receive 500 mg of methylprednasone intravenous injection once a day for 3 days, followed by once every 2 weeks, for a total of 8 times.

Group Type: ACTIVE_COMPARATOR

Glucocorticoids

Intervention Type: DRUG

500mg methylprednisolone was intravenously injected once a day for 3 consecutive days. The next treatment was carried out with an interval of 2 weeks for a total of 8 times.

Interventions

IBI311

IBI311 is a fully human anti-IGF-1R mAb. IBI311 will be provided in single-dose 10-mL glass vials as a Injection solution containing.

Intervention Type: DRUG

Glucocorticoids

500mg methylprednisolone was intravenously injected once a day for 3 consecutive days. The next treatment was carried out with an interval of 2 weeks for a total of 8 times.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Diagnosed with TAO by Bartley criteria.
• Moderate to severe patients defined by EUGOGO.
• CAS ≥4 (on the 7-item scale) for the study eye.
• Have not received glucocorticoid treatment for TAO in the past.

Exclusion Criteria

• Anticipated need for intervention due to sight-threatening complications or other significant and acute deterioration in vision.
• Combined with other lesions in the orbit.
• Receive orbital radiotherapy or surgical treatment for TED, including orbital decompression, strabismus surgery and eyelid retraction correction.
• During the screening period, if either ear has a history of tinnitus or other hearing impairment; Or abnormal pure tone audiometry results (defined as an average bone conduction hearing threshold of ≥25 dB at 0.5, 1, 2, 4 kHz or a bone conduction hearing threshold of ≥40 dB at any frequency).
• At the time of screening, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times ULN, or accompanied by active hepatitis B (defined as HBsAg positive with HBV-DNA load greater than 1000 IU/mL), or being receiving anti-hepatitis B virus treatment.
• During screening, the Glomerular Filtration Rate (GFR) was < 30 ml/min/1.73m2 (using the MDRD formula: GFR =186× serum creatinine (mg/dl) -1.154× (age) -0.203× (0.742 [if female]), unit conversion of serum creatinine: 1 μmol/L=0.0113 mg/dL); 10) At the time of screening, there was poorly controlled diabetes (defined as glycated hemoglobin ≥7.0% at the time of screening, or a new diabetes drug [oral or injection] or a dose change of the current prescribed diabetes drug > 10% within 60 days before screening).
• Screening for poorly controlled hypertension, with systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg; Or adjust the antihypertensive drug (dosage or type of drug) within 30 days before screening; Evidence of renal artery stenosis or unstable blood pressure (including orthostatic hypotension, etc.).
• At the time of screening, the 12-lead ECG showed a heart rate of < 50 beats/min or > 100 beats/min. The ECG indicated active heart disease, or the researchers believed that the abnormal ECG at the time of screening would interfere with the interpretation of the ECG results in the subsequent follow-up process. Especially, QTcF > 450 ms (for men) and QTcF > 470 ms (for women) should be excluded.
• HIV antibody or HCV antibody positive individuals or those with active syphilis (defined as those with positive non-specific syphilis antibodies or those who need anti-syphilis treatment after consultation by the infectious disease department).
• History of systemic (eg, oral or IV) steroid use of methylprednisolone for the treatment of TAO.
• Any major illness/condition or evidence of an unstable clinical condition that, in the investigators judgment, will substantially increase the risk to the participant, or confound the interpretation of safety assessments, if they were to participate in the study.
• Any other condition that, in the opinion of the investigator, would impair the ability of the participant to comply with the study procedures or impair the ability to interpret data from the participants participation in the study.
• Pregnant or lactating.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Changzheng Hospital

OTHER

Sponsor Role: lead

Responsible Party

Tuo Li, MD

Deputy Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Shanghai Changzheng Hospital

Changhua, Shanghai Municipality, China

Site Status: RECRUITING

Shanghai Changzheng Hospital

Shanghai, Shanghai Municipality, China

Site Status: NOT_YET_RECRUITING

Countries

China

Central Contacts

Tuo Li, Vice Professor

Role: CONTACT

zoe_leeto@hotmail.com

+86-13918507887

Facility Contacts

Tuo Li, MD

Role: primary

zoe_leeto@hotmail.com

+86-13918507887

Wei-yi Zhou, MD

Role: backup

weiyizhou@smmu.edu.cn

+86-18689756502

Tuo Li, Vice Professor

Role: primary

zoe_leeto@hotmail.com

+86-13918507887

Other Identifiers

ASAP-1

Identifier Type: -

Identifier Source: org_study_id