Sequential glucocorticoid therapy followed by IBI311 for active moderate-to-severe thyroid eye disease

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

This trial tests whether giving standard glucocorticoids followed by the anti-IGF-1R antibody IBI311 helps adults with active moderate-to-severe thyroid-associated ophthalmopathy (TAO).

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 64 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Shanghai Changzheng Hospital (Academic / other)
• Drugs / interventions: Tetuzumab, temumab
• Locations: 2 sites (Changhua, Shanghai Municipality and 1 other locations)
• Trial ID: NCT07152340 on ClinicalTrials.gov

What this trial studies

This Phase 4 interventional trial gives participants initial glucocorticoid (hormone) treatment followed by the monoclonal anti‑IGF‑1R antibody IBI311 to treat active moderate-to-severe TAO. Eligible participants have TAO defined by Bartley criteria, meet EUGOGO definitions of moderate-to-severe disease, and have a clinical activity score (CAS) of ≥4 in the study eye. The protocol excludes patients with sight‑threatening disease, prior orbital radiotherapy or surgery, significant hearing loss, or marked liver enzyme abnormalities, and uses clinical measures (CAS), imaging (MRI), and safety labs to monitor response and adverse events. The trial is conducted at Shanghai Changzheng Hospital with scheduled visits for treatment administration and follow-up assessments.

Who should consider this trial

Good fit: Adults with active moderate-to-severe TAO (Bartley criteria, EUGOGO definitions) who have a CAS ≥4 in the study eye and have not recently received glucocorticoid treatment for TAO are ideal candidates.

Not a fit: Patients with sight‑threatening TAO needing urgent intervention, concurrent orbital lesions, prior orbital radiotherapy or surgery, significant hearing impairment, or marked liver enzyme elevations are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this sequential approach could reduce orbital inflammation and improve vision, eye symptoms, and appearance in people with active moderate-to-severe TAO.

How similar studies have performed: Other IGF‑1R blocking antibodies, most notably teprotumumab, have shown strong clinical benefit in thyroid eye disease, so the approach of targeting IGF‑1R has supporting evidence.

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.

Where this trial is running

Changhua, Shanghai Municipality and 1 other locations

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

Study contacts

• Study coordinator: Tuo Li, Vice Professor

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