Trial Outcomes & Findings for A Safety, Tolerability, and Efficacy Study of VC-02™ Combination Product in Subjects With Type 1 Diabetes Mellitus and Hypoglycemia Unawareness (NCT NCT03163511)

Last Updated: 2024-12-03

Results Overview

Incidence of all AEs and evaluation of causality related to VC-02 combination product, the surgical procedures, and the immunosuppressive drug regimen.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

49 participants

Primary outcome timeframe

Enrollment (Visit 3, Day 1) through the Month 4 Visit

Results posted on

2024-12-03

Participant Flow

Participant milestones

Participant milestones
Measure	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	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
Overall Study STARTED	2	47
Overall Study COMPLETED	1	14
Overall Study NOT COMPLETED	1	33

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 n=2 Participants 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	Cohort 2 n=47 Participants 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	Total n=49 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	47 Participants n=7 Participants	49 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	32 years STANDARD_DEVIATION 5.66 • n=5 Participants	47.9 years STANDARD_DEVIATION 9.19 • n=7 Participants	47.2 years STANDARD_DEVIATION 9.58 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	22 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	25 Participants n=7 Participants	26 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	46 Participants n=7 Participants	48 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Canada	0 participants n=5 Participants	28 participants n=7 Participants	28 participants n=5 Participants
Region of Enrollment Belgium	0 participants n=5 Participants	5 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment United States	2 participants n=5 Participants	14 participants n=7 Participants	16 participants n=5 Participants
Duration of Type 1 Diabetes	20 years STANDARD_DEVIATION 19.8 • n=5 Participants	33.2 years STANDARD_DEVIATION 13.65 • n=7 Participants	32.7 years STANDARD_DEVIATION 13.92 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort 1 n=2 Participants 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
Incidence of All AEs in Cohort 1 Participants Total Adverse Events	33 Adverse Events
Incidence of All AEs in Cohort 1 Participants Adverse Events Related to IP	2 Adverse Events
Incidence of All AEs in Cohort 1 Participants Adverse Events Related to Surgical Procedure	24 Adverse Events
Incidence of All AEs in Cohort 1 Participants Adverse Events Related to Immunosuppression	8 Adverse Events

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort 1 n=42 Participants 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
Change in C-peptide for Cohort 2 Subjects	.1292 ng*hour/mL Standard Deviation .33157

Adverse Events

Cohort 1

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Cohort 2

Serious events: 19 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Gautham Marigowda

Vertex Pharmaceuticals, Inc

Phone: 617-961-0568

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Cohort 1 n=2 participants at risk 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	Cohort 2 n=47 participants at risk 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
Injury, poisoning and procedural complications Hematoma, post-procedural	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	6.4% 3/47 • Number of events 3 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Eye disorders Diabetic Retinopathy	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Gastrointestinal disorders Colitis	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Gastrointestinal disorders Food Poisoning	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
General disorders Adverse Drug Reaction	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	4.3% 2/47 • Number of events 2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Infections and infestations Appendicitis Perforated	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Infections and infestations Covid-19	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Infections and infestations Gastroenteritis Norovirus	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Infections and infestations Liver Abscess	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Infections and infestations Parvovirus B19 Infection	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Infections and infestations Pneumonia	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	4.3% 2/47 • Number of events 2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Infections and infestations Pyelonephritis	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Injury, poisoning and procedural complications Fall	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Injury, poisoning and procedural complications Incision Site Hematoma	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Injury, poisoning and procedural complications Post-procedural complication	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Injury, poisoning and procedural complications Post Procedural Hypotension	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Injury, poisoning and procedural complications Post Operative Ileus	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Injury, poisoning and procedural complications Procedural Nausea	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Metabolism and nutrition disorders Diabetic Ketoacidosis	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Metabolism and nutrition disorders Hypoglycemia	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	4.3% 2/47 • Number of events 5 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine Leiomyoma	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Psychiatric disorders Psychotic Disorder	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Renal and urinary disorders Acute Kidney Injury	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.

Other adverse events
Measure	Cohort 1 n=2 participants at risk 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	Cohort 2 n=47 participants at risk 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
Blood and lymphatic system disorders Anaemia	100.0% 2/2 • Number of events 4 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	29.8% 14/47 • Number of events 18 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Blood and lymphatic system disorders Haemolytic anaemia	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Blood and lymphatic system disorders Neutropenia	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	6.4% 3/47 • Number of events 3 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Blood and lymphatic system disorders Normocytic anaemia	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	4.3% 2/47 • Number of events 2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Cardiac disorders Angina pectoris	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Cardiac disorders Bundle branch block right	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Cardiac disorders Palpitations	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Cardiac disorders Tachycardia	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	4.3% 2/47 • Number of events 3 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Ear and labyrinth disorders Eustachian tube obstruction	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Ear and labyrinth disorders Motion sickness	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Ear and labyrinth disorders Tinnitus	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	4.3% 2/47 • Number of events 2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Endocrine disorders Autoimmune thyroiditis	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Endocrine disorders Hypothyroidism	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	4.3% 2/47 • Number of events 2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Eye disorders Conjunctivitis allergic	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Eye disorders Diabetic retinopathy	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Eye disorders Eye inflammation	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Eye disorders Glaucoma	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Eye disorders Vision blurred	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	6.4% 3/47 • Number of events 4 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Eye disorders Vitreous floaters	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	4.3% 2/47 • Number of events 3 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Eye disorders Vitreous haemorrhage	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	4.3% 2/47 • Number of events 2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Gastrointestinal disorders Abdominal distension	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	8.5% 4/47 • Number of events 4 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Gastrointestinal disorders Abdominal pain	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	8.5% 4/47 • Number of events 4 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	6.4% 3/47 • Number of events 6 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Gastrointestinal disorders Anal incontinence	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Gastrointestinal disorders Aphthous ulcer	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Gastrointestinal disorders Constipation	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	17.0% 8/47 • Number of events 9 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Gastrointestinal disorders Diarrhoea	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	42.6% 20/47 • Number of events 33 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Gastrointestinal disorders Faeces soft	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Gastrointestinal disorders Flatulence	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	6.4% 3/47 • Number of events 4 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Gastrointestinal disorders Food poisoning	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	4.3% 2/47 • Number of events 3 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Gastrointestinal disorders Gastrointestinal disorder	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	4.3% 2/47 • Number of events 2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Gastrointestinal disorders Irritable bowel syndrome	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Gastrointestinal disorders Nausea	100.0% 2/2 • Number of events 2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	40.4% 19/47 • Number of events 34 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.
Gastrointestinal disorders Oesophagitis	0.00% 0/2 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.	2.1% 1/47 • Number of events 1 • 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. AEs were reported on a CRF at visit 2 (Wk -4) and at every subsequent visit through end of study. The definitions used for classifying AEs/SAEs are consistent with clinicaltrials.gov definitions. Adverse Events of Special Interest (AESIs) are defined as AEs that lead to the unexpected or premature explantation of VC-02-300 or sentinel units, AEs that result in early withdrawal from study, and severe hypoglycemic events occurring after VC-02 implantation possibly or definitely related to VC-02.