A Study to Evaluate Safety, Engraftment, and Efficacy of VC-01 in Subjects With T1 Diabetes Mellitus

Study Overview
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Brief Summary
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VC01-103 will evaluate an experimental combination product, cell replacement therapy intended to provide a functional cure to subjects with Type 1 Diabetes.

Detailed Description
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This trial will test if VC-01 combination product can be implanted and maintained with safety, tolerability, and efficacy for up to Month 12/Week 52.

Official Title
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An Open-Label Phase 1/2 Study to Evaluate the Safety, Engraftment, and Efficacy of VC-01™Combination Product in Subjects With Type 1 Diabetes Mellitus [T1DM]

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Combination Product: VC-01 Combination Product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and non-pregnant women Diagnosis of T1DM for a minimum of 3 years. Stable, optimized diabetic regimen Acceptable candidate for implant and explant procedures. Willing and able to comply with protocol requirements. Meet insulin dosing requirements per protocol Exclusion Criteria: • Advanced complications associated with diabetes

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: There are two Cohorts in this study design. Cohort 1 (Phase 1) enrolls up to 30 subjects total. After Cohort 1 enrollment is completed, Cohort 2 enrollment then occurs with up to an additional 40 subjects. A total of up to 70 subjects will be enrolled under this Phase 1/2 protocol.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sentinel units (aka Cohort 1)<br>VC-01 Combination Product; Up to ten (10) VC-01 sentinels | Combination Product: VC-01 Combination Product<br>* PEC-01 cells loaded into an Encaptra Drug Delivery System<br>* Other names: PEC-Encap;|
| Experimental: Dose-finding units (aka Cohort 2)<br>VC-01 Combination Product; Up to twelve units implanted of which up to nine (9) are VC-01-DF (dose-finding) implants and the rest are VC-01 sentinels | Combination Product: VC-01 Combination Product<br>* PEC-01 cells loaded into an Encaptra Drug Delivery System<br>* Other names: PEC-Encap;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1: The Percentage of Graft Cells Present at Post-implant Time Points Relative to Pre-clinical Models | Through histology, the potential for functional engraftment of VC-01 combination product could be assessed in Cohort 1 subjects. Explanted sentinel units from subjects were processed and stained for markers identifying the number of graft cell nuclei (i.e., signifying the cells were viable). The percentage of viable graft cells in these explanted units were then compared to the percentage of viable graft cells from the pre-clinical (i.e., animal) models. These pre-clinical models are based on animal studies performed at ViaCyte (ref: internal study report). The data in Outcome Measure Data Table represent the % of viable graft cells present in the explanted sentinels compared to what was expected based on the animal model at Weeks 4, 8, 12, and 26 (e.g., At Week 4, there was an average of 18.27% viable graft cells in the participant's explants compared to what was expected based on the animal models). | Weeks 4, 8, 12 and 26 | 
| Cohort 2: The Change in AUC (Area Under Curve) From Baseline to Week 26 in C-peptide During 4-hour MMTT | Evaluation of clinical efficacy of VC-01 combination product in Cohort 2 subjects was intended by measuring C-peptide levels during a 4-hour Mixed Meal Tolerance Test (MMTT). Blood glucose and C-peptide data were collected from subjects at timepoints 0, 30, 60, 90, 120, 180, 240 minutes after ingestion of a meal (i.e., BOOST drink). These C-peptide data points could be used to create the AUC calculation. If the implanted units contained mature, insulin-producing cells, stimulated C-peptide levels would be expected to increase over the time course in reaction to the meal. | To Week 26 |