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

Обзор

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.

Вмешательства

• Препарат 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.
• Препарат 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.

Первичные конечные точки

• Percentage of participants who were overall treatment responders ater 4 times and at the end of treatment [Срок оценки: up to 24 weeks]
• Percentage of participants who were CAS categorical responders after 4 times and at the end of the treatment [Срок оценки: up to 24 weeks]
• Percentage of participants who were diplopia responders after 4 times and at the end of the treatment [Срок оценки: up to 24 weeks]
• Percentage of participants who were proptosis responders after 4 times and and the end of the treatment [Срок оценки: up to 24 weeks]
• Percentage of participants who were ATA categorical responders after 4 times and at the end of the treatment [Срок оценки: up to 24 weeks]

Вторичные конечные точки (3)

• Incidence and characterization of nonserious treatment emergent adverse events (TEAEs) during the treatment [Срок оценки: through study completion, an average of 1 year]
• change of GO-QoL from baseline after 4 times and at the end of the treatment [Срок оценки: up to 24 weeks]
• Changes of the visual field in the dark areas from baseline after 4 times and at the end of the treatment [Срок оценки: up to 24 weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• Shanghai Changzheng Hospital — Changhua
• Shanghai Changzheng Hospital — Шанхай

Идентификаторы

NCT: NCT07152340 · ASAP-1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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