A Safety, Tolerability, and Efficacy Study of VC-02™ Combination Product in Subjects With Type 1 Diabetes Mellitus and Hypoglycemia Unawareness

The purpose of this trial is to test if VC-02™ combination product can be implanted subcutaneously in subjects with Type 1 Diabetes and Hypoglycemia Unawareness and maintained safely for up to two years. It will also test if VC-02 is an effective treatment for these subjects.

• VC-02 Combination Product (Combination product), also known as PEC-Direct: PEC-01 cells loaded into a Delivery Device

Primary outcomes

• Incidence of All AEs in Cohort 1 Participants [Enrollment (Visit 3, Day 1) through the Month 4 Visit]: Incidence of all AEs and evaluation of causality related to VC-02 combination product, the surgical procedures, and the immunosuppressive drug regimen.
• Change in C-peptide for Cohort 2 Subjects [Baseline to Week 26 Visit]: Change from baseline to Week 26 in C-peptide area under the curve from 0 to 4 hours following a mixed meal tolerance test.

Sex: All, ages: 18 Years to 65 Years

Inclusion Criteria:

* Men and non-pregnant women
* Diagnosis of T1DM for a minimum of five (5) years
* Hypoglycemia unawareness or significant glycemic lability
* Stable diabetic treatment
* Willingness to use a continuous glucose meter
* Acceptable candidate for implantation

Exclusion Criteria:

* History of islet cell, kidney, and/or pancreas transplant.
* Six (6) or more severe, unexplained hypoglycemic events within six (6) months of enrollment
* Uncontrolled or untreated thyroid disease or adrenal insufficiency
* Diabetic complications such as severe kidney disease or renal dysfunction, proliferative retinopathy, diabetic foot ulcers, amputations attributable to diabetes, and/or severe peripheral neuropathy
* Non-compliance with current anti-diabetic regimen
* Detectable stimulated serum C-peptide during screening period assessment.

Participant flow

Outcome results

• Incidence of All AEs in Cohort 1 Participants (Primary), Number, Adverse Events: Cohort 1 33
• Change in C-peptide for Cohort 2 Subjects (Primary), Mean, ng*hour/mL: Cohort 2 .1292 +/- .33157

Adverse events

Time frame: Adverse events were reported for Cohort 1 participants from date of enrollment through week 26. Adverse events were reported for Cohort 2 participants from date of enrollment through week 104.

Serious adverse events by term

Other adverse events by term

221 more terms not shown.

• Results publication: Keymeulen B, De Groot K, Jacobs-Tulleneers-Thevissen D, Thompson DM, Bellin MD, Kroon EJ, Daniels M, Wang R, Jaiman M, Kieffer TJ, Foyt HL, Pipeleers D. Encapsulated stem cell-derived beta cells exert glucose control in patients with type 1 diabetes. Nat Biotechnol. 2024 Oct;42(10):1507-1514. doi: 10.1038/s41587-023-02055-5. Epub 2023 Nov 27. PMID 38012450
• Results publication: Shapiro AMJ, Thompson D, Donner TW, Bellin MD, Hsueh W, Pettus J, Wilensky J, Daniels M, Wang RM, Brandon EP, Jaiman MS, Kroon EJ, D'Amour KA, Foyt HL. Insulin expression and C-peptide in type 1 diabetes subjects implanted with stem cell-derived pancreatic endoderm cells in an encapsulation device. Cell Rep Med. 2021 Dec 2;2(12):100466. doi: 10.1016/j.xcrm.2021.100466. eCollection 2021 Dec 21. PMID 35028608
• Results publication: Ramzy A, Thompson DM, Ward-Hartstonge KA, Ivison S, Cook L, Garcia RV, Loyal J, Kim PTW, Warnock GL, Levings MK, Kieffer TJ. Implanted pluripotent stem-cell-derived pancreatic endoderm cells secrete glucose-responsive C-peptide in patients with type 1 diabetes. Cell Stem Cell. 2021 Dec 2;28(12):2047-2061.e5. doi: 10.1016/j.stem.2021.10.003. PMID 34861146

• Study Protocol (PDF, 2020-05-18)
• Statistical Analysis Plan (PDF, 2021-06-06)

• Gautham Marigowda, Study director, Vice President, Clinical Development, Vertex