Type 1 Diabetes Mellitus With Hypoglycemia
Conditions
Brief summary
VC02-101 will evaluate an experimental cell replacement therapy intended to provide a functional cure to subjects with Type 1 Diabetes and Hypoglycemia Unawareness.
Detailed description
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.
Interventions
COMBINATION_PRODUCTVC-02 Combination Product
PEC-01 cells loaded into a Delivery Device
Sponsors
California Institute for Regenerative Medicine (CIRM)
Horizon 2020 - European Commission
Vertex Pharmaceuticals Incorporated
ViaCyte
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Intervention model description
There are two Cohorts in this study design. Cohort 1 was to enroll up to 15 subjects total. After Cohort 1 enrollment was completed, Cohort 2 was to enroll up to an additional 60 subjects.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Belgium, Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 VC-02 Combination Product:
Up to ten (10) VC-02-20 implants and up to two (2) VC-02-300 implants
VC-02 Combination Product: PEC-01 cells loaded into a Delivery Device | 2 |
| Cohort 2 VC-02 Combination Product; Up to twelve units implanted of which up to ten (10) are VC-02-300 implants and the rest are VC-02-20 implants.
VC-02 Combination Product: PEC-01 cells loaded into a Delivery Device | 47 |
| Total | 49 |
Baseline characteristics
| Characteristic | Total | Cohort 2 | Cohort 1 |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 49 Participants | 47 Participants | 2 Participants |
| Age, Continuous | 47.2 years STANDARD_DEVIATION 9.58 | 47.9 years STANDARD_DEVIATION 9.19 | 32 years STANDARD_DEVIATION 5.66 |
| Duration of Type 1 Diabetes | 32.7 years STANDARD_DEVIATION 13.92 | 33.2 years STANDARD_DEVIATION 13.65 | 20 years STANDARD_DEVIATION 19.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 48 Participants | 46 Participants | 2 Participants |
| Region of Enrollment Belgium | 5 participants | 5 participants | 0 participants |
| Region of Enrollment Canada | 28 participants | 28 participants | 0 participants |
| Region of Enrollment United States | 16 participants | 14 participants | 2 participants |
| Sex: Female, Male Female | 23 Participants | 22 Participants | 1 Participants |
| Sex: Female, Male Male | 26 Participants | 25 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 47 |
| other Total, other adverse events | 2 / 2 | 47 / 47 |
| serious Total, serious adverse events | 0 / 2 | 19 / 47 |
Outcome results
Primary
Change in C-peptide for Cohort 2 Subjects
Change from baseline to Week 26 in C-peptide area under the curve from 0 to 4 hours following a mixed meal tolerance test.
Time frame: Baseline to Week 26 Visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Change in C-peptide for Cohort 2 Subjects | .1292 ng*hour/mL | Standard Deviation 0.33157 |
Primary
Incidence of All AEs in Cohort 1 Participants
Incidence of all AEs and evaluation of causality related to VC-02 combination product, the surgical procedures, and the immunosuppressive drug regimen.
Time frame: Enrollment (Visit 3, Day 1) through the Month 4 Visit
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Incidence of All AEs in Cohort 1 Participants | Total Adverse Events | 33 Adverse Events |
| Cohort 1 | Incidence of All AEs in Cohort 1 Participants | Adverse Events Related to IP | 2 Adverse Events |
| Cohort 1 | Incidence of All AEs in Cohort 1 Participants | Adverse Events Related to Surgical Procedure | 24 Adverse Events |
| Cohort 1 | Incidence of All AEs in Cohort 1 Participants | Adverse Events Related to Immunosuppression | 8 Adverse Events |