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

Naval Military Medical University (Second Military Medical University)

Status and phase: Enrolling; Phase 4

Conditions: Thyroid Associated Ophthalmopathies

Treatments: Drug: IBI311; Drug: Glucocorticoids

Study type: Interventional

Funder types: Other

Identifiers

NCT07152340

ASAP-1

Details and patient eligibility

About

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.

Enrollment: 64 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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64 participants in 2 patient groups

IBI311

Active Comparator group

Description:

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

Treatment:

Drug: IBI311

Glucocorticoid

Active Comparator group

Description:

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.

Treatment:

Drug: Glucocorticoids