Single and multiple doses of MER511 in adults with Graves' disease.

A Phase 1, First-in-Human, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Intravenous and Subcutaneous Administration of MER511 in Adults With Graves' Disease

This trial will test whether single or repeated doses of MER511 are safe and well tolerated in adults aged 18–55 who have Graves' disease, with the drug given either into a vein or under the skin.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: Merida Biosciences (Industry-sponsored)
• Drugs / interventions: teprotumumab, radiation
• Locations: 7 sites (Phoenix, Arizona and 6 other locations)
• Trial ID: NCT07305818 on ClinicalTrials.gov

What this trial studies

This Phase 1, first-in-human, multicenter study gives single ascending intravenous or subcutaneous doses (Part A) and multiple ascending subcutaneous doses (Part B) of MER511 to adults with Graves' disease using a placebo-controlled, sponsor-open, participant- and investigator-blind design. The trial will collect safety and tolerability data as well as pharmacokinetics, pharmacodynamics, and immunogenicity through scheduled clinical assessments and blood tests. Part A evaluates single-dose escalation while Part B evaluates repeat dosing in participants aged 18–55 who are on stable antithyroid drug therapy. The study is conducted at multiple U.S. sites and includes both IV and SC administration routes.

Who should consider this trial

Good fit: Adults aged 18–55 with a confirmed diagnosis of Graves' disease who are on a stable dose of antithyroid medication, meet the study weight/BMI criteria, and can comply with visit and treatment schedules are ideal candidates.

Not a fit: Patients who have had a total thyroidectomy, have hyperthyroidism from non-Graves' causes, a history of severe blood or liver toxicity from antithyroid drugs, are outside the 18–55 age range, or cannot attend required visits are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, MER511 could offer a new targeted treatment that reduces the autoimmune activity driving Graves' disease and improves thyroid control with an acceptable safety profile.

How similar studies have performed: This is a first-in-human trial of MER511, so there are no prior human data for this specific drug and the approach is largely novel, although related TSH receptor–targeting strategies have had limited preclinical study.

Eligibility criteria

Inclusion Criteria:

1. 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:

1. 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

Where this trial is running

Phoenix, Arizona and 6 other locations

• Site # 1103 — Phoenix, Arizona, United States (Recruiting)
• Site # 1101 — Hollywood, Florida, United States (Recruiting)
• Site # 1107 — Boston, Massachusetts, United States (Recruiting)
• Site # 1102 — Rochester, Minnesota, United States (Recruiting)
• Site # 1104 — Columbus, Ohio, United States (Recruiting)
• Site # 1108 — Philadelphia, Pennsylvania, United States (Recruiting)
• Site # 1105 — Webster, Texas, United States (Recruiting)

Study contacts

• Study coordinator: Clinical Operations

Conditions Graves Disease; Graves' Disease; Hyperthyroidism; Basedow disease; Exophthalmic goitre; TSHR; Autoimmune; Anti-thyroid drugs