Sequential hormone therapy followed by tetuzumab for moderate-to-severe active thyroid eye disease after steroid treatment

Efficacy and Safety of Sequential Hormone Therapy and Tetuzumab Therapy in Patients With Moderate to Severe TAO in the Active Stage After Glucocorticoid Treatment

This trial will test whether adding tetuzumab after prior steroid treatment helps people with moderate-to-severe active thyroid eye disease.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 96 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Shanghai Changzheng Hospital (Academic / other)
• Drugs / interventions: Tetuzumab
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07152366 on ClinicalTrials.gov

What this trial studies

This Phase 4 interventional study enrolls patients with moderate-to-severe active thyroid-associated ophthalmopathy who had prior glucocorticoid therapy with inadequate response. Participants receive sequential hormone management followed by tetuzumab (IBI311), a fully human anti–IGF-1R monoclonal antibody that blocks IGF-1/2 signaling and can inhibit orbital fibroblast proliferation. Outcomes will include changes in inflammatory activity (CAS), ocular symptoms such as proptosis and diplopia, safety measures, and orbital imaging (MRI) over the follow-up period. The study is conducted at Shanghai Changzheng Hospital and focuses on patients after standard steroid therapy has failed to produce satisfactory results.

Who should consider this trial

Good fit: Adults with moderate-to-severe active TAO (Clinical Activity Score ≥4) who previously received glucocorticoids but had an inadequate response are ideal candidates.

Not a fit: Patients with sight-threatening disease requiring urgent surgery, other orbital lesions, prior orbital radiotherapy or orbital surgery, or significant hearing or liver abnormalities per the exclusion criteria are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the treatment could reduce eye inflammation, lessen bulging and double vision, and improve vision and quality of life for people with active TAO.

How similar studies have performed: Yes — IGF-1R–blocking therapy for thyroid eye disease, exemplified by teprotumumab, has shown clinical benefit in prior trials, so this approach builds on that evidence.

Eligibility criteria

Inclusion 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.
* participants have received glucocorticoid treatment for TAO in the past，but did not responsive or has an unsatisfactory effect.

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 befor 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).
* 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.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai Changzheng Hospital — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Tuo Li, Vice Professor

Conditions Thyroid Associated Ophthalmopathies; IGF-1R; TED; glucocorticoids; MRI