Treatment of Active Thyroid Eye Disease With MHB018A in a Randomized, Placebo-Controlled Study

Inclusion criteria

• Body weight ≤ 120 kg.
• Clinical diagnosis of active TED with documented medical evidence of symptoms and signs in the study eye occurring within the 12 months prior to study screening. The CAS of the study eye at screening and baseline must be ≥ 3 points (7-point scale).
• Clinical diagnosis of moderate-to-severe TED at screening and baseline.
• Do not require immediate surgical ophthalmological intervention, and no corrective surgery/orbital radiotherapy is planned during the study.
• Diabetic participants must have well-controlled stable disease.

Exclusion criteria

• Participants who have: a compressive optic neuropathy of TED that requires timely and effective medical intervention; corneal abnormalities that may compromise the assessment of efficacy; previously received orbital radiotherapy or ophthalmic surgery for TED.
• Participants who received: oral or intravenous corticosteroids or corticosteroid eye drops/ointments for TED within 4 weeks prior to the first dose of study intervention; periorbital or intraorbital steroid within 3 months before the first dose of study intervention; oral or intravenous corticosteroids for reasons other than TED within 4 weeks prior to the first dose of study intervention, excluding local use (topical, nasal, inhalation); other immunosuppressive agent, including treatment with any anti-CD20 monoclonal antibody (eg, rituximab) within 6 months before the first dose of study intervention; or treatment with any other immunosuppressive agent (eg, tocilizumab) within 3 months before the first dose of study intervention; or receipt of periorbital or intraorbital administration of any such immunosuppressive agent at any time (eye drops or ointments for dry eye are permitted); previous treatment targeting IGF-1R.
• Have received: selenium and vitamin D supplements (as single agents) within 2 weeks prior to the first dose of study intervention or during the study (non-prescription multivitamin containing them is permitted), radioactive iodine treatment within 8 weeks prior to the first dose of study intervention; periocular botulinum toxin injection within 12 months prior to the first dose of study intervention; an investigational agent for any condition (including TED) within 30 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention.
• Identified pre-existing ophthalmic disease that, would preclude study participation or complicate interpretation of the study results.
• Any malignancy within 5 years prior to the first dose of study intervention, with the exception of successfully treated malignancies such as basal cell carcinoma, squamous cell carcinoma of the skin or carcinoma of the thyroid.
• Acute cardiovascular disease history or treatment within 6 months before the first dose (including but not limited to stroke, transient ischemic attack, acute myocardial infarction, unstable angina, coronary artery bypass graft surgery, percutaneous coronary intervention \[excluding diagnostic angiography\], severe arrhythmia).
• At screening, cardiac disease with 12-lead ECG indicating the presence of sinus or atrioventricular block, or the Investigator believes that the ECG abnormality at screening will interfere with the interpretation of ECG results during subsequent follow-up, especially excluding QTcF \> 450 ms (male) and QTcF \> 470 ms (female).
• Presence of poorly controlled hypertension.
• Presence at screening in either ear of an abnormal baseline PTA audiometry assessment. History of tinnitus requiring medical intervention prior or during screening or other significant ear diseases.
• Biopsy-proven or clinically suspected inflammatory bowel disease (eg, diarrhea with or without blood or rectal bleeding associated with abdominal pain or cramping/colic, urgency, tenesmus, or incontinence for more than 4 weeks without a confirmed alternative diagnosis or endoscopic or radiologic evidence of enteritis/colitis without a confirmed alternative diagnosis).
• Positive for serum virological tests, defined as: positive HIV antibody; positive HBsAg with HBV-DNA \> ULN; or positive HCV antibody with HCV-RNA \> ULN.
• Active syphilis, defined as a positive treponema pallidum-specific antibodies test (TPPA or FTA-ABS) and a consultation with an infectious disease specialist confirming the need for anti-syphilis treatment.
• Active tuberculosis, defined as a positive interferon-gamma release assay (IGRA or T-SPOT) for mycobacterium tuberculosis infection and a consultation with an infectious disease specialist confirming the need for anti- tuberculosis treatment.
• Active bacterial or fungal infection requiring systemic treatment within 7 days before the first administration.
• Participants who received or plan to receive live or attenuated live vaccines within 4 weeks before the first dose or during the study period.
• Participants who underwent major surgery within 4 weeks before the first dose or are expected to undergo surgery during the study period or within 4 weeks after the study.
• Known hypersensitivity to any of the components of MHB018A or prior hypersensitivity reactions to monoclonal antibodies.