Dysautonomia International

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

Purpose

The purpose of this study is to evaluate how well MER511 is tolerated and what side effects may occur in adults who have Graves' disease. The study drug will be administered either intravenously (into a vein in the arm) or subcutaneously (under the skin). Blood tests will be performed to investigate how the body processes the study drug and how the study drug affects the body.

Condition

Graves Disease

Eligibility

Eligible Ages: Between 18 Years and 55 Years
Eligible Sex: All
Accepts Healthy Volunteers: No

Inclusion Criteria

Adults 18 to 55 years of age, inclusive, at the time of signing the ICF 2. Documented GD diagnosis, 3. Receiving stable dose of ATD (Antithyroid drug) 4. Body weight at least 50 kg (110 lb) and body mass index (BMI) 18.0-35.0 kg/m2, inclusive 5. Women of childbearing potential must agree to use highly effective contraceptive methods 6. Men with partners of childbearing potential or who are pregnant must agree to use a condom or strict abstinence 7. Signed informed consent to participate in the study 8. Willingness and ability, in the opinion of the investigator, to comply with protocol requirements and restrictions (eg, dosing, schedule of assessments).

Exclusion Criteria

History of: 1. total thyroidectomy. 2. History of hyperthyroidism not caused by GD (eg, toxic adenoma, toxic multinodular goiter). 3. History of thyroid storm. 4. 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 2. Likely to require definitive treatment for GD (RAI therapy or thyroidectomy) during the study, based on GD history and anticipated prognosis. 3. Use of levothyroxine, desiccated thyroid extract, or T3 at any dose within 6 weeks prior to Screening. 4. History of active or chronic moderate-to-severe TED per EUropean Group On Graves' Orbitopathy (EUGOGO) criteria as judged by the investigator at Screening 5. History of TED-directed medical treatment (including IV/oral steroids, immunosuppressants, or teprotumumab), surgical treatment, and/or orbital radiation. 6. Major surgery or use of iodinated contrast within 3 months prior to planned IMP dosing. 7. Active systemic autoimmune disease requiring treatment that causes undue risk in the opinion of the investigator. 8. 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. 9. History of liver disease 10. Pregnant, breastfeeding, or planning to become pregnant during the study 11. Treatment with prohibited medications prior to planned IMP dosing or likely to require prohibited concomitant therapy during the study 12. Live vaccine(s) or mRNA vaccine(s) within 1 month prior to IMP dosing, or plans to receive such vaccines during the study 13. Treatment with any investigational drug within 6 months prior to enrollment 14. Total IgG level <700 mg/dL at Screening 15. 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 16. Estimated glomerular filtration rate (eGFR) <85 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation 17. Positive result for HIV antibody, HBsAg, or hepatitis C antibody with detectable viral RNA levels at Screening 18. Positive drug screen or positive test for alcohol 19. 12-lead ECG demonstrating any of the following at Screening: - QTcF interval >450 ms - QRS interval >120 ms - PR interval >220 ms 20. Blood pressure measurements demonstrating any of the following at Screening: - Systolic blood pressure ≥140 mmHg - Diastolic blood pressure ≥90 mmHg 21. Heart rate <45 bpm or >100 bpm 22. Donated more than 500 mL of blood in the 2 months prior to signing the ICF 23. 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 24. Refusal to adhere to lifestyle considerations as defined in the protocol 25. 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 26. Any other conditions that, in the opinion of the investigator or the sponsor, could interfere with participation in or completion of the study 27. Part B only: anyone who received IMP during Part A of the study

Study Design

Phase: Phase 1
Study Type: Interventional
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: The study will enroll cohorts of participants who will be assigned to a dose group for Part A and Part B.
Primary Purpose: Treatment
Masking: Double (Participant, Investigator)
Masking Description: Sponsor-open label, participant- and investigator-blind (Masked)