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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Active Moderate to Severe Graves' Orbitopathy
• Intervention / Treatment: Drug: SHR-1314

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. Male or female between the ages of 18 and 70 (including boundary values)
3. Onset of active GO symptoms fewer than 9 months prior to baseline.
4. 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.
5. Moderate-to-severe active GO (not sight-threatening but has an appreciable impact on daily life).
6. Does not require immediate surgical ophthalmological intervention.

Exclusion Criteria:

1. Pregnant or lactating women.
2. allergy to the study drug or to any component of the study drug.
3. Significant abnormalities in laboratory and ECG.
4. 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.
5. Corneal decompensation unresponsive to medical management.
6. Decrease in CAS of ≥ 2 points between Screening and Baseline.
7. Decrease in proptosis of ≥ 2 mm between Screening and Baseline.
8. Previous orbital irradiation or surgery for TED.
9. Any other ophthalmic disease that might interfere the study or the study result confirmed by investigator.
10. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group; SHR-1314 s.c	Drug: SHR-1314; SHR-1314 subcutaneously

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Suzhou Suncadia Biopharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 13, 2022
• Primary Completion (Anticipated): March 30, 2023
• Study Completion (Anticipated): June 14, 2023

Study Registration Dates

• First Submitted: May 23, 2022
• First Submitted That Met QC Criteria: May 23, 2022
• First Posted (Actual): May 27, 2022

Study Record Updates

• Last Update Posted (Actual): May 27, 2022
• Last Update Submitted That Met QC Criteria: May 23, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Eye Diseases; Endocrine System Diseases; Genetic Diseases, Inborn; Thyroid Diseases; Eye Diseases, Hereditary; Graves Disease; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Graves Ophthalmopathy
• Other Study ID Numbers: SHR-1314-205

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No