The primary objective of this study is to evaluate the efficacy of MHB018A injection compared with placebo in participants with active moderate-to-severe TED.
The investigational drug, MHB018A, is a monoclonal antibody that inhibits the activity of a cell surface receptor called insulin-like growth factor-1 receptor (IGF-1R). Inhibition of IGF-1R may help to reduce the inflammation and associated tissue swelling that occurs in patients with thyroid eye disease (TED). The primary objective of this study is to evaluate the efficacy of MHB018A injection compared with placebo in participants with active moderate-to-severe TED.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
84
MHB018A 450mg for subcutaneous injection once every 4 weeks (Q4W)
6 subcutaneous injections of MHB018A placebo once every 4 weeks (q4w)
Proptosis response rate at Week 24
The percentage of subjects with a reduction in proptosis of ≥2 mm in the study eye/target eye compared to baseline, without deterioration (≥2 mm) in the fellow eye.
Time frame: Week 24
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
Time frame: Baseline, up to Week 24
Percentage of subjects with CAS of 0 or 1
The percentage of subjects with a CAS (Clinical Activity Score) of 0 or 1 in the study eye/target eye. CAS ranges from 0 to 7, while higher scores mean a worse outcome.
Time frame: Week 24
Change in CAS
The mean change from baseline to Week 24 in the CAS (Clinical Activity Score) in the study eye/target eye. CAS ranges from 0 to 7, while higher scores mean worse outcome.
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.
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Time frame: 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 to Week 24
Anti-MHB018A antibody (ADA) incidence
The percentage of subjects developing anti-MHB018A antibodies.
Time frame: Up to Week 24 and at end-of-trial (EOT) visit