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

Merida Biosciences

Status and phase: Enrolling; Phase 1

Conditions: Graves Disease

Treatments: Biological: MER511 (SC); Biological: Placebo comparator (SC); Biological: MER511 (SC) for MAD; Biological: Placebo comparator (IV); Biological: MER511 (IV); Biological: Placebo comparator (SC) for MAD

Study type: Interventional

Funder types: Industry

Identifiers

NCT07305818

2025-523823-23-00 (EU Trial (CTIS) Number)

MER511-1001

Details and patient eligibility

About

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.

Full description

This Phase 1, first-in-human, multicenter study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of single and multiple ascending doses of MER511 administered to adults (18 to 55 years of age, inclusive) with GD (Graves' disease).

The study will consist of 2 sequential parts: a single ascending dose (SAD) part (Part A) followed by a multiple ascending dose (MAD) part (Part B).

Part A will employ a placebo-controlled, sponsor-open, participant- and investigator-blind design to evaluate the safety, tolerability, PK, PD, and immunogenicity of single ascending intravenous doses and a single subcutaneous dose of MER511.

Part B will employ a placebo-controlled, sponsor-open, participant- and investigator-blind design to assess the safety, tolerability, PK, PD, and immunogenicity of multiple subcutaneous doses of MER511.

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

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. 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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100 participants in 6 patient groups, including a placebo group

Part A (SAD) MER511 IV

Experimental group

Description:

For Cohorts 1-7 , each cohort participant will receive a single ascending dose of MER511 via IV administration on Day 1

Treatment:

Biological: MER511 (IV)

Part A (SAD) placebo IV

Placebo Comparator group

Description:

For Cohorts 1-7, each cohort participant will receive a single dose of placebo via IV administration on Day 1

Treatment:

Biological: Placebo comparator (IV)

Part A (SAD) MER511 SC

Experimental group

Description:

For Cohort 8, participants will receive a single dose of MER511 (determined from Cohort 1-7) via SC administration on Day 1

Treatment:

Biological: MER511 (SC)

Part A (SAD) placebo SC

Placebo Comparator group

Description:

For Cohort 8, participants will receive a single dose of placebo (determined from Cohort 1-7) via SC administration on Day 1

Treatment:

Biological: Placebo comparator (SC)

Part B (MAD) MER511 SC

Experimental group

Description:

Up to 3 cohorts of participants will receive multiple ascending doses of MER511 via SC administration assigned for their cohort on Day 1 and Day 29

Treatment:

Biological: MER511 (SC) for MAD

- Part B (MAD) placebo SC

Placebo Comparator group

Description:

Up to 3 cohorts of participants will receive multiple doses of placebo via SC administration assigned for their cohort on Day 1 and Day 29

Treatment:

Biological: Placebo comparator (SC) for MAD