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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Thyroid Ophthalmopathy
• Intervention / Treatment: Drug: Placebo; Drug: HBM9161 680 mg qw by q2w from week 13; Drug: HBM9161 680 mg qw by q2w from week 7; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Huifang Zhou; Phone Number: +86 13661901886; Email: fangzzfang@163.com
• Study Contact Backup: Name: Jing Sun; Phone Number: +86 18516204866; Email: sophiasj@126.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200011
      • Recruiting
      • Shanghai Ninth People's hospital, Shanghai Jiaotong University School of Medicine
      • Contact: Huifang Zhou; Phone Number: +8613661901886; Email: fangzzfang@163.com

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. Signed written informed consent form.
2. Male or female between the ages of 18 and 70 (including boundary values).
3. 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.
4. The active period of TED starts within 9 months prior to screening visit
5. Positive anti-TSHR antibody at screening visit.
6. Subject is willing and able to receive treatment and complete corresponding assessments as required by the protocol.

Exclusion Criteria:

1. Other uncontrolled concurrent diseases
2. Serious TED requiring surgery or radiotherapy
3. 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
4. No significant laboratory abnormalities

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Harbour BioMed (Guangzhou) Co. Ltd.
• Investigators: Principal Investigator: Huifang Zhou, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2021
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: August 3, 2021
• First Submitted That Met QC Criteria: August 19, 2021
• First Posted (Actual): August 20, 2021

Study Record Updates

• Last Update Posted (Actual): February 23, 2022
• Last Update Submitted That Met QC Criteria: February 22, 2022
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: TED
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Genetic Diseases, Inborn; Eye Diseases, Hereditary; Graves Disease; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Eye Diseases; Graves Ophthalmopathy; Thyroid Diseases
• Other Study ID Numbers: 9161.5

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes