Thyroid Associated OphthalmopathiesPhase 4NCT07152340
The Safety and Efficacy of Sequential Hormone Therapy and IBI311 Therapy in Patients With Active Moderate to Severe TAO in the Initial Treatment.
A Phase 4 study testing IBI311 and Glucocorticoids in people with Thyroid Associated Ophthalmopathies, run by Shanghai Changzheng Hospital at 2 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Thyroid Associated Ophthalmopathies
- What is being tested?
- IBI311 and Glucocorticoids
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 2 sitesChina
- Study dates
- 10 Apr 2025to 1 May 2030
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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 locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Recruiting
Shanghai Changzheng Hospital
Changhua, Shanghai Municipality, 200003
Tuo Li, MD, +86-13918507887, zoe_leeto@hotmail.com
Wei-yi Zhou, MD, +86-18689756502, weiyizhou@smmu.edu.cn
- Not yet recruiting
Shanghai Changzheng Hospital
Shanghai, Shanghai Municipality, 200003
Tuo Li, Vice Professor, +86-13918507887, zoe_leeto@hotmail.com
About this study
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.
Read more
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:
- To evaluate the efficacy of IBI311 treatment in patients with active moderate to severe TAO in the initial treatment.
- To observe the safety of IBI311 treatment in patients with active moderate to severe TAO in the initial treatment.
- 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
- Being tested
- IBI311, Glucocorticoids
- Keywords
- IGF-1R, TED, glucocorticoids, MRI imaging
- Medical subject headings
- Graves Ophthalmopathy, Insulin-Like Growth Factor I, Resistance To
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IBI311Drug
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.
GlucocorticoidsDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| IBI311 | Active comparator | 8 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 7 infusions) Receives: Drug: IBI311 |
| Glucocorticoid | Active comparator | 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. Receives: Drug: Glucocorticoids |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of participants who were overall treatment responders ater 4 times and at the end of treatment
Subjects in the study eye with a reduction of ≥2 mm in exophthalmos and a reduction of ≥2 points in the clinical activity score (CAS) from baseline, and no deterioration in the contralateral eye (an increase of ≥2 mm in exophthalmos or an increase of ≥2 points in CAS)
Measured: up to 24 weeks
Percentage of participants who were CAS categorical responders after 4 times and at the end of the treatment
The CAS is a 7-item description of clinical activity, including:
- Spontaneous orbital pain;
- Gaze evoked orbital pain;
- Eyelid swelling that is considered to be due to active (inflammatory phase) thyroid eye disease/ Graves' Ophthalmopathy or Orbitopathy (TED/GO);
- Eyelid erythema;
- Conjunctival redness that is considered to be due to active (inflammatory phase) TED/GO (ignore "equivocal" redness);
- Chemosis;
- Inflammation of caruncle or plica. Each item is scored (1=present; 0=absent) and scores for each item are summed for total score of 0 (no inflammatory symptoms) to 7 (most inflammatory symptoms).
CAS categorical responders were defined as subjects whose CAS in the study eyes decreased to 0 or 1 (with no or minimal inflammatory symptoms)
Measured: up to 24 weeks
Percentage of participants who were diplopia responders after 4 times and at the end of the treatment
Diplopia responders were defined as percentage of participants with ≥ 1 class improvement of eye motility from baseline assessed by Gorman score.
Gorman score: 1 = no diplopia, 2 =intermittent diplopia, 3 = inconstant (gaze-evoked) diplopia, 4 = constant diplopia in primary or reading position.
Measured: up to 24 weeks
Percentage of participants who were proptosis responders after 4 times and and the end of the treatment
Proptosis responders were defined as subjects whose exophthalmos in the study eye decreased by ≥2 mm compared to the baseline, and whose exophthalmos in the contralateral eye did not deteriorate (increase by ≥2 mm) at the end of the intervention observation period -1.
Measured: up to 24 weeks
Percentage of participants who were ATA categorical responders after 4 times and at the end of the treatment
Participants whose baseline ATA score of the study eye was >4, with a reduction of ≥1 grade in the ATA score, while there was no corresponding deterioration in the contralateral eye (≥1 grade deterioration).
The denominator is the number of subjects with a baseline ATA score grade >4.
Measured: up to 24 weeks
Secondary outcomes (3)
Incidence and characterization of nonserious treatment emergent adverse events (TEAEs) during the treatment
Measured: through study completion, an average of 1 year
change of GO-QoL from baseline after 4 times and at the end of the treatment
Measured: 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
Measured: up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2025
- Study start10 Apr 2025
- Primary completion30 Apr 2027 (estimated)
- Study completion1 May 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Thyroid Associated OphthalmopathiesStudies of the same condition, open and under way.
- More trials run by Shanghai Changzheng HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Changzheng Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tuo Li, MD, Shanghai Changzheng Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07152340
- Sponsor's protocol ID
- ASAP-1
- Status last verified
- Jun 2025
- First submitted
- 14 Jun 2025
- Last updated
- 3 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Safety and Efficacy of Sequential Hormone Therapy and IBI311 Therapy in Patients With Active Moderate to Severe TAO in the Initial Treatment.
- ClinicalTrials.gov ID
- NCT07152340
- Acronym / sponsor ID
- ASAP-1
- Conditions
- Thyroid Associated Ophthalmopathies
- Keywords
- IGF-1R, TED, glucocorticoids, MRI imaging
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 64 participants (estimated)
- Lead sponsor
- Shanghai Changzheng HospitalUniversity, hospital or other
- Study start
- 10 Apr 2025 (actual)
- Primary completion
- 30 Apr 2027 (estimated)
- Study completion
- 1 May 2030 (estimated)
- First posted
- 3 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To evaluate the efficacy of IBI311 treatment in patients with active moderate to severe TAO in the initial treatment.
- To observe the safety of IBI311 treatment in patients with active moderate to severe TAO in the initial treatment.
- Head-to-head comparison of sequential hormone therapy and IBI311 therapy in patients with active moderate to severe TAO in the initial treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IBI311 | Active comparator | Drug: IBI3118 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 7 infusions) |
| Glucocorticoid | Active comparator | Drug: GlucocorticoidsPatients 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IBI311IBI311 is a fully human anti-IGF-1R mAb. IBI311 will be provided in single-dose 10-mL glass vials as a Injection solution containing. | Drug | IBI311 |
| Glucocorticoids500mg 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. | Drug | Glucocorticoid |
Primary outcome
Percentage of participants who were overall treatment responders ater 4 times and at the end of treatment
Time frame: up to 24 weeks
Subjects in the study eye with a reduction of ≥2 mm in exophthalmos and a reduction of ≥2 points in the clinical activity score (CAS) from baseline, and no deterioration in the contralateral eye (an increase of ≥2 mm in exophthalmos or an increase of ≥2 points in CAS)
Percentage of participants who were CAS categorical responders after 4 times and at the end of the treatment
Time frame: up to 24 weeks
The CAS is a 7-item description of clinical activity, including: 1. Spontaneous orbital pain; 2. Gaze evoked orbital pain; 3. Eyelid swelling that is considered to be due to active (inflammatory phase) thyroid eye disease/ Graves' Ophthalmopathy or Orbitopathy (TED/GO); 4. Eyelid erythema; 5. Conjunctival redness that is considered to be due to active (inflammatory phase) TED/GO (ignore "equivocal" redness); 6. Chemosis; 7. Inflammation of caruncle or plica. Each item is scored (1=present; 0=absent) and scores for each item are summed for total score of 0 (no inflammatory symptoms) to 7 (most inflammatory symptoms). CAS categorical responders were defined as subjects whose CAS in the study eyes decreased to 0 or 1 (with no or minimal inflammatory symptoms)
Percentage of participants who were diplopia responders after 4 times and at the end of the treatment
Time frame: up to 24 weeks
Diplopia responders were defined as percentage of participants with ≥ 1 class improvement of eye motility from baseline assessed by Gorman score. Gorman score: 1 = no diplopia, 2 =intermittent diplopia, 3 = inconstant (gaze-evoked) diplopia, 4 = constant diplopia in primary or reading position.
Percentage of participants who were proptosis responders after 4 times and and the end of the treatment
Time frame: up to 24 weeks
Proptosis responders were defined as subjects whose exophthalmos in the study eye decreased by ≥2 mm compared to the baseline, and whose exophthalmos in the contralateral eye did not deteriorate (increase by ≥2 mm) at the end of the intervention observation period -1.
Percentage of participants who were ATA categorical responders after 4 times and at the end of the treatment
Time frame: up to 24 weeks
Participants whose baseline ATA score of the study eye was >4, with a reduction of ≥1 grade in the ATA score, while there was no corresponding deterioration in the contralateral eye (≥1 grade deterioration). The denominator is the number of subjects with a baseline ATA score grade >4.
3 secondary outcomes
Incidence and characterization of nonserious treatment emergent adverse events (TEAEs) during the treatment
Time frame: through study completion, an average of 1 year
change of GO-QoL from baseline after 4 times and at the end of the treatment
Time frame: 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
Time frame: up to 24 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing IBI311 and Glucocorticoids in people with Thyroid Associated Ophthalmopathies, run by Shanghai Changzheng Hospital at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tuo Li, Vice Professor (+86-13918507887, zoe_leeto@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of participants who were overall treatment responders ater 4 times and at the end of treatment (time frame: up to 24 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2025.