A Study to Evaluate the Efficacy and Safety of HBM9161 on Moderate to Severe Thyroid Eye Disease

Study Overview
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Brief Summary
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Primary Objective: To preliminarily evaluate the efficacy of the treatment regimen of HBM9161 680 mg administered subcutaneously weekly and sequentially every other week for 12 weeks in Chinese patients with active moderate to severe TED.

Detailed Description
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This is a multicenter, randomized, double-blind and placebo-controlled study. The investigational drug is HBM9161 injection, with the indication of TED. Subjects will be randomized to treatment group I, treatment group II, or placebo group. Subjects in treatment group 1 will receive HBM9161 680 mg subcutaneously once weekly (qw) for 12 doses; Subjects in treatment group 2 will receive HBM9161 680 mg subcutaneously once weekly (qw) for 6 doses, followed by HBM9161 680 mg subcutaneously once every two weeks (q2w) for 3 doses; Subjects in placebo group will receive placebo subcutaneously once weekly (qw) for 12 doses. After the 12-week dosing period, there will be a 5-week follow-up period.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Phase 2/3 Operational Seamless Design Clinical Study to Evaluate the Efficacy and Safety of HBM9161 Subcutaneous Injection in Chinese Patients With Active, Moderate to Severe Thyroid Eye Disease (TED)

Conditions
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Thyroid Ophthalmopathy

Intervention / Treatment
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* Drug: HBM9161 680 mg qw by q2w from week 13
* Drug: Placebo
* Drug: HBM9161 680 mg qw by q2w from week 7
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent form. Male or female between the ages of 18 and 70 (including boundary values). Active TED associated with a clinical diagnosis of Graves' disease or Hashimoto's thyroiditis with CAS ≥ 3 at the screening visit and baseline (both on a 7-item scale) in the eye with the most severe proptosis. The active period of TED starts within 9 months prior to screening visit Positive anti-TSHR antibody at screening visit. Subject is willing and able to receive treatment and complete corresponding assessments as required by the protocol. Exclusion Criteria: Other uncontrolled concurrent diseases Serious TED requiring surgery or radiotherapy Suffer from autoimmune diseases or ophthalmic conditions other than TED that, in the opinion of the investigator, would impact the assessment of the study drug No significant laboratory abnormalities

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HBM9161 680 mg qw by q2w from week 13<br>Subcutaneous injection; HBM9161 680 mg qw from week 13 | Drug: HBM9161 680 mg qw by q2w from week 13<br>* HBM9161 680 mg qw by q2w from week 13<br>|
| Experimental: HBM9161 680 mg qw by q2w from week 7<br>Subcutaneous injection; HBM9161 680 mg qw by q2w from week 7 | Drug: HBM9161 680 mg qw by q2w from week 7<br>* HBM9161 680 mg qw by q2w from week 7<br>|
| Experimental: Placebo<br>Subcutaneous injection; Placebo | Drug: Placebo<br>* Placebo<br>|
| Experimental: Placebo qw by HBM9161 680mg qw from week 12<br>Placebo qw by HBM9161 680mg qw from week 12 | Drug: Placebo<br>* Placebo qw by HBM9161 680mg qw from week 12<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proptosis responder rates of the treatment groups and placebo group at Week 12 | Proptosis responder rates of the treatment groups and placebo group at Week 12 | At week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of subjects with a CAS value of 0 or 1 in the study eye | The percentage of subjects with a CAS value of 0 or 1 in the study eye | At week 6, week 12, week 18 and week 24 | 
| The change from Baseline in proptosis measurement in the study eye | The change from Baseline in proptosis measurement in the study eye | At week 6, week 12, week 18 and week 24 | 
| Composite responder rate | Composite responder rate | At week 6, week 12, week 18 and week 24 | 
| Diplopia response rate | Diplopia response rate | At week 6, week 12, week 18 and week 24 | 
| The change from baseline in the Graves' Ophthalmopathy Quality of Life (GO-QoL) Questionnaire visual function score and psychosocial function score | The change from baseline in the Graves' Ophthalmopathy Quality of Life (GO-QoL) Questionnaire visual function score and psychosocial function score | At week 6, week 12, week 18 and week 24 | 
| The changes in proptosis responder rate over time | The changes in proptosis responder rate over time | From week 1 to week 24 | 
| The change from baseline in quantitative measurement of orbital structures by MRI, including exophthalmos values, fatty tissue thickness of inner side in eye balls, thickness of extraocular muscles. All the above parameters will be measured in millimeter | The change from baseline in quantitative measurement of orbital structures by MRI, including exophthalmos values, fatty tissue thickness of inner side in eye balls, thickness of extraocular muscles. All the above parameters will be measured in millimeter | At week 12, week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TED