This is a multicenter, open-label extension (OLE) study of MHB018A in subjects with moderate-to-severe TED.
The primary objective of this study is to evaluate the improvement in proptosis from baseline (defined as the most recent measurement prior to the first dose in this study) following treatment with MHB018A Injection in subjects with active or chronic TED who previously received placebo in either the MHB018A-P-301 or MHB018A-P-302 studies, and the safety and tolerability of MHB018A Injection in TED subjects.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
258
MHB018A 450mg for subcutaneous injection once every 4 weeks (Q4W)
Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, China
Proptosis Responder Rate at Week 24
The proptosis response rate at Week 24 in the study eye for subjects with active or chronic TED who received MHB018A placebo in either the MHB018A-P-301 or MHB018A-P-302 studies: the proportion of subjects achieving a reduction of ≥2 mm in proptosis from baseline (defined as the most recent measurement prior to the first dose in this study) in the study eye, without deterioration in the other eye (defined as an increase in proptosis of ≥2 mm).
Time frame: Week 24
TED relapse rate
TED relapse rate from treatment discontinuation to relapse (for subjects with active or chronic TED who previously received and completed 24 weeks of MHB018A Injection treatment in either the MHB018A-P-301 or MHB018A-P-302 study, meet the disease relapse enrollment criteria for this study during the safety follow-up period, and receive retreatment with MHB018A Injection)
Time frame: From baseline up to Week 24
TED relapse time
TED relapse time from treatment discontinuation to relapse (for subjects with active or chronic TED who previously received and completed 24 weeks of MHB018A Injection treatment in either the MHB018A-P-301 or MHB018A-P-302 study, meet the disease relapse enrollment criteria for this study during the safety follow-up period, and receive retreatment with MHB018A Injection)
Time frame: Up to Week 24 and at end-of-trial (EOT) visit
Overall response rate
The percentage of subjects with ≥2-points in Clinical Activity Score (CAS) reduction and ≥2 mm reduction in proptosis from baseline, provided there is no corresponding deterioration (≥2-points/mm increase) in CAS or proptosis in the fellow eye.
Time frame: Week 24
Change in proptosis
Change from baseline in proptosis in the study eye as measured by exophthalmometer at Week 24
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Time frame: Baseline, up to Week 24
Percentage of subjects with CAS of 0 or 1
The percentage of subjects with a CAS of 0 or 1 in the study eye/target eye.
Time frame: Week 24
Change in CAS
The mean change from baseline to Week 24 in the CAS in the study eye/target eye.
Time frame: Week 24
Diplopia response rate
The percentage of subjects with a reduction in diplopia severity by ≥1 grade.
Time frame: Week 24
Change in Quality of Life (GO-QOL) Scores
The mean change in scores from the Graves' Ophthalmopathy Quality of Life questionnaire compared to baseline. The GO-QoL is a self-filled questionnaire containing 16 items. The raw scores for items 1-8 and items 9-16 are summed separately, each yielding a total raw score ranging from 8 to 24. Each raw score is then transformed into a 0-100 scale using the following formula: Total Score = (Raw Score - 8) ÷ 16 × 100. Higher scores indicate better quality of life.
Time frame: Up tp Week 24
Pharmacokinetic Parameter Trough Concentration for MHB018A
Trough concentration (Ctrough) will be assessed using non-compartmental methods in participants randomized to the MHB018A group.
Time frame: Up tp Week 24
Incidence of Adverse Events (AEs) During Treatment
Including Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and AEs leading to early study withdrawal, along with laboratory tests, 12-lead ECGs, vital signs, and physical examinations.
Time frame: Up to Week 24 and at end-of-trial (EOT) visit