NEXUS Study: A Study to Test Single and Multiple Doses of MER511 Given to Adults With Graves' Disease

Exclusion Criteria38

• History of:
• total thyroidectomy.
• History of hyperthyroidism not caused by GD (eg, toxic adenoma, toxic multinodular goiter).
• History of thyroid storm.
• History of agranulocytosis, anemia, leukopenia, thrombocytopenia, vasculitis, or liver toxicity due to prior ATD therapy Treatment with RAI therapy within 12 months prior to Screening
• Likely to require definitive treatment for GD (RAI therapy or thyroidectomy) during the study, based on GD history and anticipated prognosis.
• Use of levothyroxine, desiccated thyroid extract, or T3 at any dose within 6 weeks prior to Screening.
• History of active or chronic moderate-to-severe TED per EUropean Group On Graves' Orbitopathy (EUGOGO) criteria as judged by the investigator at Screening
• History of TED-directed medical treatment (including IV/oral steroids, immunosuppressants, or teprotumumab), surgical treatment, and/or orbital radiation.
• Major surgery or use of iodinated contrast within 3 months prior to planned IMP dosing.
• Active systemic autoimmune disease requiring treatment that causes undue risk in the opinion of the investigator.
• History of cardiovascular, respiratory, renal, gastrointestinal, endocrinological (other than GD), hematological, immunodeficiency, or neurological disorders that may constitute a risk when taking the IMP or interfere with data interpretation.
• History of liver disease
• Pregnant, breastfeeding, or planning to become pregnant during the study
• Treatment with prohibited medications prior to planned IMP dosing or likely to require prohibited concomitant therapy during the study
• Live vaccine(s) or mRNA vaccine(s) within 1 month prior to IMP dosing, or plans to receive such vaccines during the study
• Treatment with any investigational drug within 6 months prior to enrollment
• Total IgG level \<700 mg/dL at Screening
• Any of the following at Screening (confirmed by single repeat measurement, if deemed necessary):
• ALT or AST \>1.5 × ULN
• Total bilirubin \>1.5 × ULN
• Estimated glomerular filtration rate (eGFR) \<85 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation
• Positive result for HIV antibody, HBsAg, or hepatitis C antibody with detectable viral RNA levels at Screening
• Positive drug screen or positive test for alcohol
• lead ECG demonstrating any of the following at Screening:
• QTcF interval \>450 ms
• QRS interval \>120 ms
• PR interval \>220 ms
• Blood pressure measurements demonstrating any of the following at Screening:
• Systolic blood pressure ≥140 mmHg
• Diastolic blood pressure ≥90 mmHg
• Heart rate \<45 bpm or \>100 bpm
• Donated more than 500 mL of blood in the 2 months prior to signing the ICF
• Current enrollment or past participation within 30 days or 5 half-lives (whichever is longer) prior to signing the ICF in any other clinical trial involving an IMP
• Refusal to adhere to lifestyle considerations as defined in the protocol
• Employee of the investigator, clinic, or sponsor with direct involvement in the proposed study or other studies under the direction of the investigator or clinic, as well as family members of the employee or investigator
• Any other conditions that, in the opinion of the investigator or the sponsor, could interfere with participation in or completion of the study
• Part B only: anyone who received IMP during Part A of the study