Efficacy and Safety of SHR-1314 by Subcutaneous Injection in Active Moderate to Severe Graves' Orbitopathy Patients

Study Overview
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Brief Summary
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This is a single-arm, prospective, open-label, Phase II study that explored the efficacy and safety of SHR-1314 in active moderate to severe Graves' Orbitopathy. The study consists of a 6-week screening period, a 16-week treatment period, and a 12-week follow-up period. Eighteen adult patients with active moderate to severe Graves' Orbitopathy will be enrolled. Eligible subjects will receive SHR-1314 subcutaneously. The primary endpoint was the proptosis responder rate and will be evaluated at 16weeks.

Official Title
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A Single-arm, Open-label, Prospective Phase II Study to Evaluate the Efficacy and Safety of SHR-1314 by Subcutaneous Injection in Active Moderate to Severe Graves' Orbitopathy Patients

Conditions
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Active Moderate to Severe Graves' Orbitopathy

Intervention / Treatment
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* Drug: SHR-1314


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must be able to understand and communicate with the investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study assessment is performed. Male or female between the ages of 18 and 70 (including boundary values) Onset of active GO symptoms fewer than 9 months prior to baseline. Clinical diagnosis of Graves' disease associated with active GO with a CAS ≥ 3 (on the 7-item scale) for the most severely affected eye(study eye) at Screening and Baseline. Moderate-to-severe active GO (not sight-threatening but has an appreciable impact on daily life). Does not require immediate surgical ophthalmological intervention. Exclusion Criteria: Pregnant or lactating women. allergy to the study drug or to any component of the study drug. Significant abnormalities in laboratory and ECG. Decreased best corrected visual acuity due to optic neuropathy as defined by a decrease in vision of 2 lines on the Snellen chart, new visual field defect, or color defect secondary to optic nerve involvement within the last 6 months. Corneal decompensation unresponsive to medical management. Decrease in CAS of ≥ 2 points between Screening and Baseline. Decrease in proptosis of ≥ 2 mm between Screening and Baseline. Previous orbital irradiation or surgery for TED. Any other ophthalmic disease that might interfere the study or the study result confirmed by investigator. Patients with serious, progressive and uncontrolled cardiovascular, liver, kidney, lung, gastrointestinal, hematopoietic, endocrine, nervous and psychiatric diseases, or other conditions that considered inappropriate for patients to participate this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: SHR-1314 s.c in the treatment group, no placebo
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>SHR-1314 s.c | Drug: SHR-1314<br>* SHR-1314 subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the proptosis responder rate | Proptosis responder is defined as a ≥ 2 mm reduction from Baseline in proptosis in the study eye, without deterioration [≥ 2 mm increase] of proptosis in the fellow eye) | week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving response in reduction of clinical activity score(CAS) | reduction of CAS is defined as reduction of ≥ 2 points of CAS from Baseline to Week16. | week 16 | 
| Overall responder rate | Overall responder rate is defined as percentage of subjects with≥ 2-point reduction in CAS AND ≥ 2 mm reduction in proptosis from Baseline, provided there is no corresponding deterioration [≥ 2-point/mm increase] in CAS or proptosis in the fellow eye at Week 16 | week 16 | 
| The percentage of subjects with a CAS value of 0 or 1 in the study eye | the clinical activity score of subject is 0 or 1. | week 16 | 
| The mean change from Baseline to Week 16 in proptosis measurement in the study eye | Average change in proptosis in study eye. | week 16 | 
| Diplopia response rate at Week16 | Proportion of participants with Baseline diplopia > 0 and a reduction of ≥ 1 grade with no corresponding deterioration (≥ 1 grade worsening) in the fellow eye at Week 16. | week 16 | 
| The mean change from Baseline to Week 16 in the GO-QoL score | Average change in the Graves' ophthalmopathy quality of life questionnaire (GO-QOL) score. The GO-QoL contains 8 questions on visual functioning and 8 questions on appearance; answers on each subscale are transformed to scores ranging from 0 (worst) to 100 (best). | week 16 |