Trial Outcomes & Findings for A Study to Evaluate Safety, Engraftment, and Efficacy of VC-01 in Subjects With T1 Diabetes Mellitus (NCT NCT04678557)

Last Updated: 2023-10-18

Results Overview

Through histology, the potential for functional engraftment of VC-01 combination product could be assessed in Cohort 1 subjects. Explanted sentinel units from subjects were processed and stained for markers identifying the number of graft cell nuclei (i.e., signifying the cells were viable). The percentage of viable graft cells in these explanted units were then compared to the percentage of viable graft cells from the pre-clinical (i.e., animal) models. These pre-clinical models are based on animal studies performed at ViaCyte (ref: internal study report). The data in Outcome Measure Data Table represent the % of viable graft cells present in the explanted sentinels compared to what was expected based on the animal model at Weeks 4, 8, 12, and 26 (e.g., At Week 4, there was an average of 18.27% viable graft cells in the participant's explants compared to what was expected based on the animal models).

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

31 participants

Primary outcome timeframe

Weeks 4, 8, 12 and 26

Results posted on

2023-10-18

Participant Flow

Participant milestones

Participant milestones
Measure	8 or 10 Sentinel Units Implanted (Cohort 1) VC-01 combination product is comprised of PEC-01 cells loaded into an Encaptra Drug Delivery System. In Cohort 1 of this study, 8 or 10 VC-01 sentinel units were surgically implanted in each subject during a single procedure. Sentinel units are smaller versions of the product not intended to provide efficacy but are instead explanted at various timepoints over the course of the study and examined histologically.	9 Dose Finding Units Implanted (Cohort 2) A total of 12 VC-01 units were implanted in each of the Cohort 2 subjects in a single surgical procedure. Of those units, 9 were VC-01 Dose Finding (DF) units. DF units are larger than sentinels and intended to remain implanted during the duration of participation in the trial to assess efficacy. The remaining 3 units implanted were the smaller VC-01 sentinel units intended for explant at various time points for analysis histologically.
Overall Study STARTED	17	14
Overall Study COMPLETED	16	0
Overall Study NOT COMPLETED	1	14

Reasons for withdrawal

Reasons for withdrawal
Measure	8 or 10 Sentinel Units Implanted (Cohort 1) VC-01 combination product is comprised of PEC-01 cells loaded into an Encaptra Drug Delivery System. In Cohort 1 of this study, 8 or 10 VC-01 sentinel units were surgically implanted in each subject during a single procedure. Sentinel units are smaller versions of the product not intended to provide efficacy but are instead explanted at various timepoints over the course of the study and examined histologically.	9 Dose Finding Units Implanted (Cohort 2) A total of 12 VC-01 units were implanted in each of the Cohort 2 subjects in a single surgical procedure. Of those units, 9 were VC-01 Dose Finding (DF) units. DF units are larger than sentinels and intended to remain implanted during the duration of participation in the trial to assess efficacy. The remaining 3 units implanted were the smaller VC-01 sentinel units intended for explant at various time points for analysis histologically.
Overall Study Withdrawal by Subject	1	0
Overall Study Lack of Efficacy	0	13
Overall Study Safety Evaluation	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sentinel Units (Aka Cohort 1) n=17 Participants VC-01 Combination Product; Up to ten (10) VC-01 sentinels VC-01 Combination Product: PEC-01 cells loaded into an Encaptra Drug Delivery System	Dose-finding Units (Aka Cohort 2) n=14 Participants VC-01 Combination Product; Up to twelve units implanted of which up to nine (9) are VC-01-DF (dose-finding) implants and the rest are VC-01 sentinels VC-01 Combination Product: PEC-01 cells loaded into an Encaptra Drug Delivery System	Total n=31 Participants Total of all reporting groups
Age, Continuous	37.0 years STANDARD_DEVIATION 13.11 • n=5 Participants	44.1 years STANDARD_DEVIATION 8.53 • n=7 Participants	40.2 years STANDARD_DEVIATION 11.7 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=5 Participants	14 Participants n=7 Participants	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	17 participants n=5 Participants	14 participants n=7 Participants	31 participants n=5 Participants
Body Mass Index	24.98 kg/m^2 STANDARD_DEVIATION 2.992 • n=5 Participants	27.28 kg/m^2 STANDARD_DEVIATION 2.807 • n=7 Participants	26.00 kg/m^2 STANDARD_DEVIATION 3.09 • n=5 Participants
Duration of Type 1 Diabetes	19.4 years STANDARD_DEVIATION 12.08 • n=5 Participants	26.4 years STANDARD_DEVIATION 11.24 • n=7 Participants	22.5 years STANDARD_DEVIATION 12.0 • n=5 Participants

PRIMARY outcome

Timeframe: Weeks 4, 8, 12 and 26

Population: For each timepoint, explanted sentinel units containing PEC-01 cells from the 17 subjects were stained and evaluated for graft cell survival (i.e., viability). Not all subjects had units explanted at every timepoint, and units explanted that had "de minimus" graft cell survival (i.e., minimal, \< 500 cells, \< 4% of pre-clinical controls) could not be evaluated and were not included in the summary table.

Outcome measures

Outcome measures
Measure	Sentinel Units (Aka Cohort 1) n=81 VC01 sentinels (contains PEC-01 cells) VC-01 Combination Product; Up to ten (10) VC-01 sentinels VC-01 Combination Product: PEC-01 cells loaded into an Encaptra Drug Delivery System
Cohort 1: The Percentage of Graft Cells Present at Post-implant Time Points Relative to Pre-clinical Models Week 4	18.27 %cells in sentinels rel to animal models Standard Deviation 13.94
Cohort 1: The Percentage of Graft Cells Present at Post-implant Time Points Relative to Pre-clinical Models Week 8	6.23 %cells in sentinels rel to animal models Standard Deviation 4.63
Cohort 1: The Percentage of Graft Cells Present at Post-implant Time Points Relative to Pre-clinical Models Week 12	7.58 %cells in sentinels rel to animal models Standard Deviation 7.27
Cohort 1: The Percentage of Graft Cells Present at Post-implant Time Points Relative to Pre-clinical Models Week 26	8.02 %cells in sentinels rel to animal models Standard Deviation 8.09

PRIMARY outcome

Timeframe: To Week 26

Population: Stimulated C-peptide data from the MMTT showed every value from baseline and Week 26 samples at all timepoints to be "undetectable" (\<0.1 ng/mL) except for one subject for whom the AUC could be calculated. Analyzing the data was deemed futile because the number of surviving graft cells was noted as insufficient for establishing the biological critical mass. The change from baseline to Week 26 in AUC for this one subject is provided below.

Evaluation of clinical efficacy of VC-01 combination product in Cohort 2 subjects was intended by measuring C-peptide levels during a 4-hour Mixed Meal Tolerance Test (MMTT). Blood glucose and C-peptide data were collected from subjects at timepoints 0, 30, 60, 90, 120, 180, 240 minutes after ingestion of a "meal" (i.e., BOOST drink). These C-peptide data points could be used to create the AUC calculation. If the implanted units contained mature, insulin-producing cells, stimulated C-peptide levels would be expected to increase over the time course in reaction to the meal.

Outcome measures

Outcome measures
Measure	Sentinel Units (Aka Cohort 1) n=1 Participants VC-01 Combination Product; Up to ten (10) VC-01 sentinels VC-01 Combination Product: PEC-01 cells loaded into an Encaptra Drug Delivery System
Cohort 2: The Change in AUC (Area Under Curve) From Baseline to Week 26 in C-peptide During 4-hour MMTT	0.325 ng*h/mL

Adverse Events

Sentinel Units (Aka Cohort 1)

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Dose-finding Units (Aka Cohort 2)

Serious events: 3 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sentinel Units (Aka Cohort 1) n=17 participants at risk VC-01 Combination Product; Up to ten (10) VC-01 sentinels VC-01 Combination Product: PEC-01 cells loaded into an Encaptra Drug Delivery System	Dose-finding Units (Aka Cohort 2) n=14 participants at risk VC-01 Combination Product; Up to twelve units implanted of which up to nine (9) are VC-01-DF (dose-finding) implants and the rest are VC-01 sentinels VC-01 Combination Product: PEC-01 cells loaded into an Encaptra Drug Delivery System
Pregnancy, puerperium and perinatal conditions Vanishing Twin Syndrome	5.9% 1/17 • Number of events 1 • Cohort 1 subjects reported adverse events over approximately 7 months (e.g., subjects implanted/treated for 6 months). Cohort 2 subjects reported adverse events over approximately 13 months (e.g., subjects implanted/treated for 12 months). AE/SAE Definitions used are the same as the ClinicalTrials.gov definitions. Systematic Assessment of AE Collection was used (e.g., regular investigator assessment was required at each study visit per protocol). In addition, routine monitoring visits to the site provided 100% source document verification of the AE Collection.	0.00% 0/14 • Cohort 1 subjects reported adverse events over approximately 7 months (e.g., subjects implanted/treated for 6 months). Cohort 2 subjects reported adverse events over approximately 13 months (e.g., subjects implanted/treated for 12 months). AE/SAE Definitions used are the same as the ClinicalTrials.gov definitions. Systematic Assessment of AE Collection was used (e.g., regular investigator assessment was required at each study visit per protocol). In addition, routine monitoring visits to the site provided 100% source document verification of the AE Collection.
Gastrointestinal disorders Small Intestinal Obstruction	0.00% 0/17 • Cohort 1 subjects reported adverse events over approximately 7 months (e.g., subjects implanted/treated for 6 months). Cohort 2 subjects reported adverse events over approximately 13 months (e.g., subjects implanted/treated for 12 months). AE/SAE Definitions used are the same as the ClinicalTrials.gov definitions. Systematic Assessment of AE Collection was used (e.g., regular investigator assessment was required at each study visit per protocol). In addition, routine monitoring visits to the site provided 100% source document verification of the AE Collection.	7.1% 1/14 • Number of events 1 • Cohort 1 subjects reported adverse events over approximately 7 months (e.g., subjects implanted/treated for 6 months). Cohort 2 subjects reported adverse events over approximately 13 months (e.g., subjects implanted/treated for 12 months). AE/SAE Definitions used are the same as the ClinicalTrials.gov definitions. Systematic Assessment of AE Collection was used (e.g., regular investigator assessment was required at each study visit per protocol). In addition, routine monitoring visits to the site provided 100% source document verification of the AE Collection.
Metabolism and nutrition disorders Hypoglycemia	0.00% 0/17 • Cohort 1 subjects reported adverse events over approximately 7 months (e.g., subjects implanted/treated for 6 months). Cohort 2 subjects reported adverse events over approximately 13 months (e.g., subjects implanted/treated for 12 months). AE/SAE Definitions used are the same as the ClinicalTrials.gov definitions. Systematic Assessment of AE Collection was used (e.g., regular investigator assessment was required at each study visit per protocol). In addition, routine monitoring visits to the site provided 100% source document verification of the AE Collection.	7.1% 1/14 • Number of events 1 • Cohort 1 subjects reported adverse events over approximately 7 months (e.g., subjects implanted/treated for 6 months). Cohort 2 subjects reported adverse events over approximately 13 months (e.g., subjects implanted/treated for 12 months). AE/SAE Definitions used are the same as the ClinicalTrials.gov definitions. Systematic Assessment of AE Collection was used (e.g., regular investigator assessment was required at each study visit per protocol). In addition, routine monitoring visits to the site provided 100% source document verification of the AE Collection.
Nervous system disorders Subarachnoid hemorrhage	0.00% 0/17 • Cohort 1 subjects reported adverse events over approximately 7 months (e.g., subjects implanted/treated for 6 months). Cohort 2 subjects reported adverse events over approximately 13 months (e.g., subjects implanted/treated for 12 months). AE/SAE Definitions used are the same as the ClinicalTrials.gov definitions. Systematic Assessment of AE Collection was used (e.g., regular investigator assessment was required at each study visit per protocol). In addition, routine monitoring visits to the site provided 100% source document verification of the AE Collection.	7.1% 1/14 • Number of events 1 • Cohort 1 subjects reported adverse events over approximately 7 months (e.g., subjects implanted/treated for 6 months). Cohort 2 subjects reported adverse events over approximately 13 months (e.g., subjects implanted/treated for 12 months). AE/SAE Definitions used are the same as the ClinicalTrials.gov definitions. Systematic Assessment of AE Collection was used (e.g., regular investigator assessment was required at each study visit per protocol). In addition, routine monitoring visits to the site provided 100% source document verification of the AE Collection.

Other adverse events

Additional Information

Medical Information

Vertex

Phone: 617-341-6777

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place