NEXUS Study: A Study to Test Single and Multiple Doses of MER511 Given to 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

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.

Study Overview

• Status: Recruiting
• Conditions: Graves Disease
• Intervention / Treatment: Biological: MER511 (IV); Biological: Placebo comparator (IV); Biological: MER511 (SC); Biological: Placebo comparator (SC); Biological: MER511 (SC) for MAD; Biological: Placebo comparator (SC) for MAD

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Operations; Phone Number: +1 339-255-3030; Email: clinicaltrials@meridabio.com

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Recruiting
      • Site # 1103
      • Contact: Principal Investigator; Phone Number: 339-255-3030; Email: clinicaltrials@meridabio.com
  • Florida
    • Hollywood, Florida, United States, 33024
      • Recruiting
      • Site # 1101
      • Contact: Principal Investigator; Phone Number: 339-255-3030; Email: clinicaltrials@meridabio.com
    • Wesley Chapel, Florida, United States, 33544
      • Recruiting
      • Site # 1109
      • Contact: Principal Investigator; Phone Number: 339-255-3030; Email: clinicaltrials@meridabio.com
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Site # 1107
      • Contact: Principal Investigator; Phone Number: 339-255-3030; Email: clinicaltrials@meridabio.com
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Site # 1102
      • Contact: Principal Investigator; Phone Number: 339-255-3030; Email: clinicaltrials@meridabio.com
  • Ohio
    • Columbus, Ohio, United States, 43203
      • Recruiting
      • Site # 1104
      • Contact: Principal Investigator; Phone Number: 339-255-3030; Email: clinicaltrials@meridabio.com
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Site # 1108
      • Contact: Principal Investigator; Phone Number: 339-255-3030; Email: clinicaltrials@meridabio.com
  • Texas
    • Webster, Texas, United States, 77598
      • Recruiting
      • Site # 1105
      • Contact: Principal Investigator; Phone Number: 339-255-3030; Email: clinicaltrials@meridabio.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A (SAD) MER511 IV; For Cohorts 1-7 , each cohort participant will receive a single ascending dose of MER511 via IV administration on Day 1	Biological: MER511 (IV); Participants will receive a single dose of MER511 on Day 1
Placebo Comparator: Part A (SAD) placebo IV; For Cohorts 1-7, each cohort participant will receive a single dose of placebo via IV administration on Day 1	Biological: Placebo comparator (IV); Participants will receive a single dose of Placebo on Day 1
Experimental: Part A (SAD) MER511 SC; For Cohort 8, participants will receive a single dose of MER511 (determined from Cohort 1-7) via SC administration on Day 1	Biological: MER511 (SC); Participants will receive a single dose of MER511 on Day 1
Placebo Comparator: Part A (SAD) placebo SC; For Cohort 8, participants will receive a single dose of placebo (determined from Cohort 1-7) via SC administration on Day 1	Biological: Placebo comparator (SC); Participants will receive a single dose of Placebo on Day 1
Experimental: Part B (MAD) MER511 SC; 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	Biological: MER511 (SC) for MAD; Participants will receive multiple ascending doses of MER511 via SC administration assigned for their cohort on Day 1 and Day 29
Placebo Comparator: - Part B (MAD) placebo SC; 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	Biological: Placebo comparator (SC) for MAD; Participants will receive multiple doses of placebo via SC administration assigned for their cohort on Day 1 and Day 29

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with TEAEs (Treatment-emergent adverse events)	Adverse events that start or worsen in severity after the start of study drug will be categorized as TEAEs	- Part A (SAD) Cohorts: Day 1 up to Week 16 - Part B (MAD) Cohorts: Day 1 up to Week 24
Number of participants with clinically significant changes in ECGs, vital signs, clinical laboratory values, and physical examination	Incidence of clinically significant abnormalities in ECGs, vital signs, clinical laboratory values, and physical examination	- Part A (SAD) Cohorts: Day 1 up to Week 16 - Part B (MAD) Cohorts: Day 1 up to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum tmax (Time to maximum concentration)	Measurement of the time to maximum observed concentration	- Part A (SAD) Cohorts: Day 1 (Week 0 dosing day) Through Week 16 - Part B (MAD) Cohorts: Day 1 (Week 0 dosing day) Through Week 24
Serum AUCinf (area under concentration-time curve from time zero to infinity)	Measurement of area under concentration-time curve from time zero to infinity	Part A (SAD) Only: Day 1 (Week 0) Dosing Through Week 16
Serum AUC0-tau (area under concentration-time curve during the dosing interval)	Measurement of area under concentration-time curve during the dosing interval	Part B (MAD) Only: Day 1 (Week 0) Dosing Through Week 24
Number of participants with ADAs (Anti-drug antibody)	Blood samples will be collected to evaluate the immunogenicity of MER511 in participants with GD (Graves' disease)	- Part A (SAD) Cohorts: Day 1 (Week 0) Dosing Through Week 16 or Early Discontinuation - Part B (MAD) Cohorts: Day 1 (Week 0) Dosing Through Week 24
Serum Cmax (Maximum observed concentration)	Measurement of the maximum observed concentration	- Part A (SAD) Cohorts: Day 1 (Week 0 dosing day) through Week 16- Part B (MAD) Cohorts: Day 1 (Week 0 dosing Day) Through Week 24

Collaborators and Investigators

• Sponsor: Merida Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2025
• Primary Completion (Estimated): July 24, 2028
• Study Completion (Estimated): July 24, 2028

Study Registration Dates

• First Submitted: December 12, 2025
• First Submitted That Met QC Criteria: December 12, 2025
• First Posted (Actual): December 26, 2025

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Hyperthyroidism; Autoimmune; Graves' Disease; Autoimmune thyroid disease; Basedow disease; Exophthalmic goitre; TSHR; Anti-thyroid drugs
• Additional Relevant MeSH Terms: Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Eye Diseases; Exophthalmos; Orbital Diseases; Goiter; Thyroid Diseases; Graves Disease; Hyperthyroidism
• Other Study ID Numbers: MER511-1001; 2025-523823-23-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No