Thyroid Eye Disease
Conditions
Brief summary
This is a multicenter, randomized, open-label, active-controlled Phase IV clinical trial in participants with active thyroid eye disease (TED). Approximately 92 eligible participants will be randomized to the teprotumumab N01 group and the intravenous glucocorticoid (IVGC) group in a 1:1 ratio on Day 1. The randomization stratification factor is diplopia at baseline (Gorman diplopia score ≥1 vs. Gorman diplopia score = 0).
Interventions
BIOLOGICALTeprotumumab N01
A total of 8 intravenous infusions of Teprotumumab N01 injection will be administered: 10 mg/kg on Day1, followed by 20 mg/kg in Week3-21, once every 3 weeks(Q3W).
DRUGMethylprednisolone
A total of 12 intravenous infusions of methylprednisolone will be administered: 500 mg for the first six doses (on Day 1 and weekly throughout Weeks 1-5), and then 250 mg for the following six doses (weekly throughout Weeks 6-11). Based on disease deterioration and treatment response, participants will receive individualized treatment after IVGC therapy.
Sponsors
Innovent Biologics (Suzhou) Co. Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Written informed consent. 2. Male or female subject between the ages of 18 and 80 years at screening. 3. Weight between 45 kg and 100 kg. 4. Moderate-to-severe active TED: * CAS ≥ 3 in the study eye at screening and baseline; * Usually associated with at least two of the following: lid retraction ≥ 2 mm, moderate or severe soft tissue involvement, exophthalmos ≥ 3 mm above normal, and/or inconstant or constant diplopia; * ≤ 12 months since the onset of active TED symptoms according to subjects' chief complaint or medical record at screening; 5. Exophthalmos ≥ 16 mm in the study eye at baseline. 6. Infertile female participants or fertile female participants with negative blood pregnancy test results during the screening period and agree to take contraceptive measures from screening to 120 days after the last dose; male participants should agree to use contraceptive measures from screening to 120 days after the last dose.
Exclusion criteria
Key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The proptosis responder rate of the study eye | Week15 | The proptosis response rate of the study eye was defined as the percentage of participants with a ≥ 2 mm reduction in proptosis of the study eye from baseline and without a ≥ 2 mm increase in proptosis of the fellow eye. Proptosis assessment: protrusion of the eye from the orbital rim as measured using a Hertel exophthalmometer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The diplopia response rate | Weeks 15, 24 and 48 | The diplopia response rate was defined as the percentage of participants with an improvement in Gorman diplopia score of ≥ 1 grade |
| The diplopia resolution rate | Weeks 15, 24 and 48 | The diplopia resolution rate was defined as the percentage of participants with Gorman diplopia score = 0 |
| Change from baseline in proptosis of the fellow eye | Weeks 15, 24 and 48 | Proptosis assessment: protrusion of the eye from the orbital rim as measured using a Hertel exophthalmometer. |
| Change from baseline of the Graves' Ophthalmopathy Quality of Life (GO-QoL) questionnaire score | Weeks 15, 24 and 48 | Change from baseline of the total GO-QoL score, GO-QoL visual functioning subscale and appearance subscale scores. The scores for the visual functioning and appearance subscales should be considered independently. A higher score on each subscale denotes a better quality of life. |
| Number, incidence, severity, and correlation with the investigational drug or treatment of all ocular and systemic adverse events (AE), treatment-emergent adverse events (TEAE), and serious adverse events (SAE). | After receiving Teprotumumab N01 or IVGC treatment for 48 weeks | All AE，TEAE and SAE listed above are reference data used to support the safety and tolerability assessment of the drug. |
| Change from baseline in proptosis of the study eye | Weeks 15, 24 and 48 | Proptosis assessment: protrusion of the eye from the orbital rim as measured using a Hertel exophthalmometer. |
| The overall response rate of the study eye | Weeks 15, 24 and 48 | The overall response rate of the study eye was defined as the percentage of participants with a decrease in Clinical Activity Score \[CAS\] of ≥ 2 points from baseline in the study eye and a decrease in proptosis of ≥ 2 mm from baseline in the study eye, without deterioration in the fellow eye \[deterioration is defined as an increase in CAS of ≥ 2 points or an increase in proptosis of ≥ 2 mm\]. |
| Change from baseline in proptosis of the study eye on MRI imaging | Week15 | Proptosis of the study eye as measured on orbital MRI imaging. |
| The proptosis response rate of the study eye | Weeks 24 and 48 | The proptosis response rate of the study eye was defined as the percentage of participants with a ≥ 2 mm reduction in proptosis of the study eye from baseline and without a ≥ 2 mm increase in proptosis of the fellow eye. |
| The composite effective rate of the study eye | Weeks 15, 24 and 48 | The composite effective rate of the study eye was defined as the percentage of participants with improvement in 2 or more of the 4 indicators \[a. ≥2 mm reduction of lid aperture; b. ≥1 point decrease in the five-item CAS (redness of eyelids, swelling of eyelids, redness of conjunctiva, chemosis, and swelling of caruncle or plica); c. ≥2 mm reduction in proptosis; d. ≥8° improvement in ocular motility\] in the study eye and without corresponding deterioration in the fellow eye. |
| Rate of CAS of 0 or 1 in the study eye | Weeks 15, 24 and 48 | According to the 7-item European Group on Graves' Ophthalmopathy (EUGOGO) amendment, CAS was used to evaluate clinical activity. For each of the following items, one point is given: spontaneous orbital pain, gaze evoked orbital pain, eyelid swelling, eyelid erythema, conjunctival redness, chemosis, and inflammation of caruncle or plica. The sum of these points is the total score, with 0 indicating no clinical activity and 7 indicating the most severe clinical activity. |
| Change from baseline in CAS of the study eye | Weeks 15, 24 and 48 | According to the 7-item European Group on Graves' Ophthalmopathy (EUGOGO) amendment, CAS was used to evaluate clinical activity. For each of the following items, one point is given: spontaneous orbital pain, gaze evoked orbital pain, eyelid swelling, eyelid erythema, conjunctival redness, chemosis, and inflammation of caruncle or plica. The sum of these points is the total score, with 0 indicating no clinical activity and 7 indicating the most severe clinical activity. |
Countries
China
Contacts
CONTACTLily Zhang
Outcome results
None listed