Type 2 Diabetes Diabetes
Conditions
Interventions
The Rejuva Device System is a sterile, endoscopic ultrasound intraparenchymal infusion (EUS-IPI) system with no active components. It is composed of a needle, fluid lumen within a sheath, handle and s
Sponsors
Fractyl Health, Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Signed and dated written informed consent in accordance with Good Clinical Practice (GCP) and local legislation. Participant must consent to the following: To perform CGM and SMBG testing, which the participant will record in a diary throughout the entire study, complete clinical outcome assessments and comply with study visits and other study procedures. Age 35 to 70 years (inclusive).Male and post-menopausal or surgically sterile female. Participants assigned male at birth (AMAB) are required to use a condom and their assigned female at birth (AFAB) partners must use a highly effective method of contraception for the study duration and for at least 1 year after RJVA-001 infusion.Diagnosis of Type 2 DiabetesBody Mass index (BMI) 27 to 40 kg/m2HbA1c: 7.0% to 10.0% inclusive and a FPG =270 mg/dL at Visit 1 and reconfirmed at Visit 2 and 3. Participants are 1) taking once-weekly injectable, once-daily injectable or oral GLP-1RA at the maximum tolerated maintenance dose and 2) taking 1 to 3 permitted non-insulin GLAs other than GLP-1RA. Permitted non-insulin GLAs include: MetforminThiazolidinediones (TZD)Sodium-glucose cotransporter 2 inhibitors (SGLT2i)Random C-peptide of >1.0 ng/mL (>0.3 nmol/L)Normal thyroid function, defined as thyroid stimulating hormone (TSH) =6 mIU/L and =0.4 mIU/L; participants may be on thyroid replacement as long as thyroid stimulating hormone is within these normal limits.Normal calcitonin at Screening, Visit 1.Based on Investigator’s judgement, continuous dose escalation or modification of participant’s current treatment regimen is deemed unacceptable.Participant has deferred insulin therapy. The Investigator has documented the rationale for insulin use and education about insulin therapy has been provided to the participant.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 up to Week 52.
Exclusion criteria
Exclusion criteria: Diagnosis of Type 1 diabetes or history of ketoacidosis, monogenic diabetes (neonatal diabetes or maturity onset diabetes of the young), or latent autoimmune diabetes of adults (LADA), or presence of 1 or more islet cell autoantibodies:Glutamic acid decarboxylase (GAD) antibodyIslet antigen (IA-2)Zinc transporter 8 (ZnT8) History of dose-limiting persistent adverse side effects from GLP-1RA useHistory of non-adherence to diabetes treatment in the previous 6 months, as determined by the InvestigatorKnown history of diabetic retinopathyActive systemic infection (eg, Helicobacter pylori 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 participationHistory of chronic or acute pancreatitis (except for gallstone pancreatitis treated by cholecystectomy), at high risk of acute pancreatitis per Investigator (including history of familial pancreatitis), or fasting triglycerides >600 mg/dL (>3.4 mmol/L) in the 3 months prior to Visit 1Family history of hemochromatosis or cystic fibrosis, as self-reported by the participants will be documented. Symptomatic cholelithiasis (gallstones) or cholecystitis in the previous 6 months unless treated by cholecystectomyGeneral contraindications to deep or conscious sedation or general anesthesia or high risk as determined by anesthesiologist (eg, American Society of Anesthesiology score 4 or higher) Contraindications to upper gastrointestinal (GI) endoscopy, including:Known history of a structural or functional disorder of the esophagus, including any swallowing disorder, esophageal chest pain disorders, or drug-refractory esophageal reflux symptoms, active and uncontrolled gastroesophageal reflux disease (GERD) (grade 3 esophagitis or greater)Known history of a structural or functional disorder of the stomach or duodenum, including gastric ulcer, chronic gastritis, gastric varices, hiatal hernia (a large hiatal hernia or type II and higher paraoesophageal hernia), stomach cancer or any other disorder of the stomach. Does not apply to participants diagnosed with gastric ulcer or gastritis solely due to Helicobacter pylori infection that was successfully treated.Previous GI surgery that could affect the ability to access the pancreas such as Billroth II, Roux-en-Y gastric bypass, gastric sleeveActive gastric implants (eg, gastric balloon, gastric stimulator, etc.)Clinically significant upper GI conditions (esophageal, gastric, and intestinal) such as ulcers, polyps, varices, strictures, congenital, acquired intestinal telangiectasiaHistory of tuberculosisImmunization with live vaccines within 30 days prior to screening, Visit 1.Known hypersensitivity or allergy to eggs, milk, wheat, or [13C]-labeled Spirulina substratesAny contraindications to the infusate to be deliveredHistory of hepatic decompensation/acute liver disease (except for non-alcoholic steatohepatitis) in the last 6 months prior to Visit 1, acute or chronic active hepatitis B or C (except if hepatitis C is cured), alcoholic or autoimmune chronic hepatitis. Known portal hypertension.History of symptomatic heart failure with reduced or preserved ejection fraction (New York Heart
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the safety and tolerability of RJVA-001 when delivered in the pancreas using the Rejuva Device System | — |
Secondary
| Measure | Time frame |
|---|---|
| Percent of procedures where target anatomy (body and/or tail of pancreas) was able to be accessedPercent of procedures where intended dose of infusate was delivered AEs and serious adverse events (SAEs) related to the Rejuva System Device or EUS-IPI that occur from device introduction to device removal AEs and SAEs related to the Rejuva System Device or EUS-IPI that occur from device removal up to 6 months post-procedure | — |
Countries
Australia, Germany, Netherlands
Contacts
Public ContactJ. Caplan
Fractyl Health, Inc.
Outcome results
None listed