Clinical Trials

Inclusion Criteria:

• Participant, male or female, is ≥ 18 years of age at the time of informed consent.
• Participant is willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
• Participant has a diagnosis of GSD1a with confirmation by G6PC gene sequencing.
  • Note: genetic confirmation of GSD1a is needed by the time of study drug administration. However, all Screening procedures and other assessments may proceed based on clinical diagnosis alone.
• Participant has a documented history of ≥ 1 hypoglycemic event with blood glucose < 60 mg/dL (< 3.3 mmol/L) and/or symptoms of hypoglycemia in the absence of acute illness, with at least one such event in the 4 weeks before signing the ICF.
• Participant’s aspartate aminotransferase and alanine aminotransferase values are < 1.5 × the upper limit of normal (may be repeated up to 2 times during Screening at the discretion of the Investigator).
• Participant has an absolute neutrophil count ≥ 1500/mm^3, a platelet count ≥ 150,000/mm^3, and hemoglobin ≥ 10 g/dL.
• Participant, if female, must meet the following criteria:
  • Not of childbearing potential (a follicle-stimulating hormone [FSH] level may be measured at the discretion of the Investigator to confirm postmenopausal status); or
  • If of childbearing potential, must be either not sexually active or using at least one method of highly effective contraception (failure rate < 1% per year when used consistently and correctly) at least 28 days before administration of mRNA-3745 and for 28 days following administration of mRNA-3745.
• Participant, if female, must have a negative serum pregnancy test (beta human chorionic gonadotropin [β-hCG]) at Screening and a negative urine pregnancy test on Day -1.
• Participant, if male and sexually active with a female partner of childbearing potential, must agree to practice a highly effective method of contraception for 28 days following the dose of mRNA-3745.

Exclusion Criteria: 

• Participant has genetically confirmed diagnosis of another inborn error of metabolism in addition to GSD1a.
• Participant has previously received gene therapy for GSD1a.
• Participant has a history of liver transplantation.
• Participant has a diagnosis of hepatocellular carcinoma.
• Participant has at least 1 hepatic adenoma > 5 cm in size.
• Participant has at least 1 hepatic adenoma with an increase in size of > 2 cm OR a finding of > 5 newly diagnosed hepatic adenomas, when compared with the last imaging obtained with a consistent technique (magnetic resonance imaging [MRI]) performed in the preceding 2 years, when available.
• Participant has a diagnosis of type 1 or type 2 diabetes mellitus.
• Participant has positive serology for human immunodeficiency virus (HIV-1, HIV-2), hepatitis B surface antigen (HBsAg+) with hepatitis B surface antibody (HBsAb-), and/or hepatitis C at Screening.
• Participant has blood triglyceride levels > 750 mg/dL at Screening (May be repeated up to 2 times during Screening at the discretion of the Investigator).
• Participant has estimated glomerular filtration rate < 60 mL/min/1.73 m^2 as estimated by the modification of diet in renal disease equation for adults (calculated by the Modification of Diet in Renal Disease Study Equation).
• Participant has a clinically relevant abnormal 12-lead ECG at Screening or Day ˗1 confirmed by repeat (including prolonged Fridericia corrected QT interval, defined as > 450 ms for males and > 470 ms for females, AV block second degree or higher, permanent pacemaker, or implantable cardioverter defibrillator).
• Participant for whom MRI and contrast media would be contraindicated.
• Inability to adhere to alcohol prohibition from 14 days before through 21 days after the study drug administration.
• Participant has any other clinically significant medical condition that in the Investigator’s opinion could interfere with the interpretation of study results, pose additional risk in administering study drug, or limit the participant’s participation in the study.

Eligibility last updated 9/10/21. Questions regarding updates should be directed to the study team contact.