Adeno-associated virus serotype 9 containing the human GCG gene for Type 2 diabetes mellitus

Inclusion criteria

• {"criterion_text":"- 1. Signed and dated written informed consent in accordance with Good Clinical Practice and local legislation.\n- 10. Normal calcitonin level as stated in the study protocol.\n- 11. Based on Investigator’s judgement, continuous dose escalation or modification of participant’s current treatment regimen is deemed unacceptable.\n- 12. Participant has deferred insulin therapy.\n- 13. Able to tolerate a once-weekly injectable, once-daily injectable or oral GLP-1RA treatment as evidenced by ongoing treatment and benefit from GLP-1RAs at an efficacious dose.\n- 14. Participants must be willing to abstain from semen/blood donation through 1 year after RJVA-001 injection.\n- 15. Participants must be willing to abstain from alcohol use until completion of the sirolimus taper.\n- 16.\tParticipants must agree not to initiate any new or intensive diet or exercise regimens and/or any new weight loss medications during study participation.\n- 2. Age 35 to 70 years (inclusive).\n- 3. Agree to use appropriate form of contaception for the study duration and for at least 1 year after RJVA-001 infusion.\n- 4. Diagnosis of Type 2 Diabetes.\n- 5. Body mass index as indicated in the study protocol.\n- 6. Fasting plasma glucose and hemoglobin A1c levels as stated in the study protocol.\n- 7. Participants are taking glucagon-like peptide-1 receptor agonists (GLP-1RA) at the maximum tolerated maintenance dose and taking permitted non-insulin glucose lowering agents other than GLP-1RA.\n- 8. Random C-peptide level as stated in the study protocol.\n- 9. Normal thyroid function as defined in the study protocol."}

Exclusion criteria

• {"criterion_text":"- 1.\tDiagnosis of Type 1 diabetes or history of ketoacidosis, monogenic diabetes or latent autoimmune diabetes of adults or presence of 1 or more islet cell autoantibodies.\n- 18. History of clinically significant valvular heart disease or severe aortic stenosis.\n- 19. Acute coronary syndrome, stroke or transient ischemic attack as stated in the study protocol.\n- 2. History of dose-limiting persistent adverse side effects from GLP-1RA use.\n- 20. History of severe peripheral vascular disease.\n- 21. History of active malignancy or partial remission from clinically significant malignancy, personal or familial history of medullary thyroid carcinoma as stated in the study protocol.\n- 22. Suspected GI malignancy.\n- 23. History of blood dyscrasias or any disorders causing hemolysis or unstable erythrocytes.\n- 24. History of alcohol or illicit substance abuse as stated in the study protocol.\n- 25. Intake of an investigational drug within 5 half-lives prior to visit 1 or active participation in another clinical trial of an investigational drug or device.\n- 26. Contraindication to systemic steroids or sirolimus.\n- 10. General contraindications to deep or conscious sedation or general anesthesia or high risk as determined by anesthesiologist.\n- 27. Participant is on a weight loss program and is not in the weight maintenance phase, or is on a GLP-1 weight loss medication.\n- 28. Participant has poorly controlled hypertension as defined in the study protocol.\n- 29. Any other clinical or mental condition which, in the opinion of the Investigator, would jeopardize participant’s safety or makes participant a poor candidate for clinical trial participation.\n- 3. History of non-adherence to diabetes treatment in the previous 6 months, as determined by the Investigator.\n- 30. Laboratory and Radiographic Exclusions as stated in the study protocol.\n- 4. Known history of diabetic retinopathy.\n- 5. Active systemic infection or undergoing treatment for recent infection. Does not apply to completely treated infection.\n- 6. Condition(s) requiring systemic immunomodulation or whose immune status makes the participant a poor candidate for clinical trial participation.\n- 7. History of chronic or acute pancreatitis, or elevated fasting triglycerides as stated in the study protocol.\n- 8. Family history of hemochromatosis or cystic fibrosis, as self-reported by the participants will be documented.\n- 11. Contraindications to upper gastrointestinal (GI) endoscopy.\n- 9. Symptomatic cholelithiasis or cholecystitis unless treated by cholecystectomy.\n- 31. Concomitant Medication Exclusions as stated in the study protocol.\n- 12. History of tuberculosis.\n- 13. Immunization with live vaccines within 30 days prior to screening, Visit 1.\n- 14. Known hypersensitivity or allergy to eggs, milk, wheat, or [13C]-labeled Spirulina substrates.\n- 15. Any contraindications to the infusate to be delivered.\n- 16. History of hepatic decompensation/acute liver disease, acute or chronic active hepatitis B or C, alcoholic or autoimmune chronic hepatitis as stated in the study protocol. Known portal hypertension.\n- 17. History of symptomatic heart failure with reduced or preserved ejection fraction."}

Primary endpoints

• {"endpoint_text":"- Incidence, severity, dose-relationship of Adverse Events and changes in laboratory evaluations.","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- 1. Change in transgene secretion and glycemic parameters.","definition_or_measurement_approach":""}
• {"endpoint_text":"- 2. Anti-AAV9 antibody titers, anti-GLP-1 antibody titers and enzyme-linked immunosorbent spot for AAV9 and GLP-1.","definition_or_measurement_approach":"Measured by antibody titers and ELISpot assays for AAV9 and GLP-1."}
• {"endpoint_text":"- 3. Digital polymerase chain reaction for AAV9 in samples.","definition_or_measurement_approach":"Measured by digital PCR detection of AAV9 in biological samples."}
• {"endpoint_text":"- 4. Change from Baseline parameters using continuous glucose monitoring.","definition_or_measurement_approach":"Measured by continuous glucose monitoring parameters compared to baseline."}

Netherlands

Earliest CTIS Part Ii Submission Date

30-03-2026

Latest Decision Or Authorization Date

23-04-2026

Processing Time Days

24

Number Of Sites

1

Number Of Participants

15

Primary sponsor

Full Name

Fractyl Health Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Medpace Finland Oy

Responsibilities

codes: 1,10,11,12,15 (Providing Devices, Medical Monitoring and Safety Oversight.),2,3,4,5,6,8

Third parties

• {"country":"United States","full_name":"Precision Digital Health Inc.","duties_or_roles":"BGM and CGM device services","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Cellular Technology Ltd.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Cerba Research","duties_or_roles":"code: 4","organisation_type":"Industry"}
• {"country":"Netherlands","full_name":"Healthlink Europe B.V.","duties_or_roles":"Medical Device Distribution","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"CAIRN DIAGNOSTICS","duties_or_roles":"code: 4","organisation_type":"Industry"}
• {"country":"United States","full_name":"StageBio","duties_or_roles":"code: 4","organisation_type":"Industry"}
• {"country":"Finland","full_name":"Medpace Finland Oy","duties_or_roles":"codes: 1,10,11,12,15 (Providing Devices, Medical Monitoring and Safety Oversight.),2,3,4,5,6,8","organisation_type":"Pharmaceutical company"}