The RJVA-001 First in Human Trial in Adults with Inadequately Controlled Type 2 Diabetes.

Prior treatment

• 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.
• Contraindication to systemic steroids or sirolimus.
• Participant is on a weight loss program and is not in the weight maintenance phase, or is on a GLP-1 weight loss medication.
• History of non-adherence to diabetes treatment in the previous 6 months, as determined by the Investigator.
• Concomitant Medication Exclusions as stated in the study protocol.
• Immunization with live vaccines within 30 days prior to screening, Visit 1.

Other illness

• Diagnosis 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.
• History of clinically significant valvular heart disease or severe aortic stenosis.
• Acute coronary syndrome, stroke or transient ischemic attack as stated in the study protocol.
• History of dose-limiting persistent adverse side effects from GLP-1RA use.
• History of severe peripheral vascular disease.
• 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.
• Suspected GI malignancy.
• History of blood dyscrasias or any disorders causing hemolysis or unstable erythrocytes.
• History of alcohol or illicit substance abuse as stated in the study protocol.
• Participant has poorly controlled hypertension as defined in the study protocol.
• 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.
• Known history of diabetic retinopathy.
• Active systemic infection or undergoing treatment for recent infection. Does not apply to completely treated infection.
• Condition(s) requiring systemic immunomodulation or whose immune status makes the participant a poor candidate for clinical trial participation.
• History of chronic or acute pancreatitis, or elevated fasting triglycerides as stated in the study protocol.
• Family history of hemochromatosis or cystic fibrosis, as self-reported by the participants will be documented.
• History of tuberculosis.
• Known hypersensitivity or allergy to eggs, milk, wheat, or [13C]-labeled Spirulina substrates.
• 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.

Lab values

• Laboratory and Radiographic Exclusions as stated in the study protocol.
• History of symptomatic heart failure with reduced or preserved ejection fraction.

Other

• General contraindications to deep or conscious sedation or general anesthesia or high risk as determined by anesthesiologist.
• Contraindications to upper gastrointestinal (GI) endoscopy.
• Symptomatic cholelithiasis or cholecystitis unless treated by cholecystectomy.
• Any contraindications to the infusate to be delivered.

• Signed and dated written informed consent in accordance with Good Clinical Practice and local legislation.
• Normal calcitonin level as stated in the study protocol.
• Based on Investigator’s judgement, continuous dose escalation or modification of participant’s current treatment regimen is deemed unacceptable.
• Participant has deferred insulin therapy.
• 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.
• Participants must be willing to abstain from semen/blood donation through 1 year after RJVA-001 injection.
• Participants must be willing to abstain from alcohol use until completion of the sirolimus taper.
• Participants must agree not to initiate any new or intensive diet or exercise regimens and/or any new weight loss medications during study participation.
• Age 35 to 70 years (inclusive).
• Agree to use appropriate form of contaception for the study duration and for at least 1 year after RJVA-001 infusion.
• Diagnosis of Type 2 Diabetes.
• Body mass index as indicated in the study protocol.
• Fasting plasma glucose and hemoglobin A1c levels as stated in the study protocol.
• 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.
• Random C-peptide level as stated in the study protocol.
• Normal thyroid function as defined in the study protocol.