Graves Disease
Conditions
Keywords
Graves' Disease, Hyperthyroidism, Basedow disease, Exophthalmic goitre, TSHR, Autoimmune, Anti-thyroid drugs, Autoimmune thyroid disease
Brief summary
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.
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 65 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.
Interventions
BIOLOGICALMER511 (IV)
Participants will receive a single dose of MER511 on Day 1
BIOLOGICALPlacebo comparator (IV)
Participants will receive a single dose of Placebo on Day 1
BIOLOGICALMER511 (SC)
Participants will receive a single dose of MER511 on Day 1
BIOLOGICALPlacebo comparator (SC)
Participants will receive a single dose of Placebo on Day 1
BIOLOGICALMER511 (SC) for MAD
Participants will receive multiple ascending doses of MER511 via SC administration assigned for their cohort on Day 1 and Day 29
BIOLOGICALPlacebo comparator (SC) for MAD
Participants will receive multiple doses of placebo via SC administration assigned for their cohort on Day 1 and Day 29
Sponsors
Merida Biosciences
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Sponsor-open label, participant- and investigator-blind (Masked)
Intervention model description
The study will enroll cohorts of participants who will be assigned to a dose group for Part A and Part B.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Adults 18 to 65 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. Current 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 within 3 months prior to Screening, or per required prohibited concomitant therapy washout criteria in the protocol (whichever is longer) 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 within 3 months or 5 half-lives (whichever is longer) 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) \<75 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 3 months 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with TEAEs (Treatment-emergent adverse events) | - Part A (SAD) Cohorts: Day 1 up to Week 16 - Part B (MAD) Cohorts: Day 1 up to Week 24 | Adverse events that start or worsen in severity after the start of study drug will be categorized as TEAEs |
| Number of participants with clinically significant changes 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 | Incidence of clinically significant abnormalities in ECGs, vital signs, clinical laboratory values, and physical examination |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Cmax (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 | Measurement of the maximum observed concentration |
| Serum tmax (Time to maximum 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 | Measurement of the time to maximum observed concentration |
| Serum AUCinf (area under concentration-time curve from time zero to infinity) | Part A (SAD) Only: Day 1 (Week 0) Dosing Through Week 16 | Measurement of area under concentration-time curve from time zero to infinity |
| Serum AUC0-tau (area under concentration-time curve during the dosing interval) | Part B (MAD) Only: Day 1 (Week 0) Dosing Through Week 24 | Measurement of area under concentration-time curve during the dosing interval |
| Number of participants with ADAs (Anti-drug antibody) | - 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 | Blood samples will be collected to evaluate the immunogenicity of MER511 in participants with GD (Graves' disease) |
Countries
Spain, United States
Contacts
CONTACTClinical Operations
Outcome results
None listed