Study NCT04678557
A Study to Evaluate Safety, Engraftment, and Efficacy of VC-01 in Subjects With T1 Diabetes Mellitus (VC01-103)
Submitted Date:  July 6, 2023 (v7)
Quality Control Review Has Not Concluded

Note: The results information displayed below has not completed the quality control (QC) review process. ClinicalTrials.gov must post results information for applicable clinical trials (ACTs) within 30 days of submission, even if the submission has not completed the QC review process. The study sponsor or investigator is responsible for ensuring the results information meets the QC review criteria.

This submission includes brief standardized QC review comments added by the National Library of Medicine (NLM). These comments indicate the location of apparent errors, deficiencies, or inconsistencies. For more information, see the Final Rule (42 CFR Part 11) Information page.

General Comments

Quality Control Review Comment provided by the National Library of Medicine:

  1. This record has new issues that must be addressed.
Open or close this module Study Identification
Unique Protocol ID: VC01-103
Brief Title: A Study to Evaluate Safety, Engraftment, and Efficacy of VC-01 in Subjects With T1 Diabetes Mellitus (VC01-103)
Official Title: An Open-Label Phase 1/2 Study to Evaluate the Safety, Engraftment, and Efficacy of VC-01™Combination Product in Subjects With Type 1 Diabetes Mellitus [T1DM]
Secondary IDs:
Open or close this module Study Status
Record Verification: July 2023
Overall Status: Terminated [Insufficient functional product engraftment]
Study Start: June 25, 2019
Primary Completion: November 12, 2021 [Actual]
Study Completion: November 19, 2021 [Actual]
First Submitted: November 30, 2020
First Submitted that
Met QC Criteria:		 December 16, 2020
First Posted: December 22, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
Last Update Posted: July 27, 2023 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: ViaCyte
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: VC01-103 will evaluate an experimental combination product, cell replacement therapy intended to provide a functional cure to subjects with Type 1 Diabetes.
Detailed Description: This trial will test if VC-01 combination product can be implanted and maintained with safety, tolerability, and efficacy for up to Month 12/Week 52.
Open or close this module Conditions
Conditions: Type 1 Diabetes
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Other
Study Phase: Phase 1/Phase 2
Interventional Study Model: Sequential Assignment
There are two Cohorts in this study design. Cohort 1 (Phase 1) enrolls up to 30 subjects total. After Cohort 1 enrollment is completed, Cohort 2 enrollment then occurs with up to an additional 40 subjects. A total of up to 70 subjects will be enrolled under this Phase 1/2 protocol.
Number of Arms: 2
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 31 [Actual]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Sentinel units (aka Cohort 1)
VC-01 Combination Product; Up to ten (10) VC-01 sentinels
 Combination Product: VC-01 Combination Product
PEC-01 cells loaded into an Encaptra Drug Delivery System
Other Names:
  • PEC-Encap
Experimental: Dose-finding units (aka Cohort 2)
VC-01 Combination Product; Up to twelve units implanted of which up to nine (9) are VC-01-DF (dose-finding) implants and the rest are VC-01 sentinels
 Combination Product: VC-01 Combination Product
PEC-01 cells loaded into an Encaptra Drug Delivery System
Other Names:
  • PEC-Encap
Open or close this module Outcome Measures
[See Results Section.]
Primary Outcome Measures:
1. Cohort 1: The Percentage of Graft Cells Present at Post-implant Time Points Relative to Pre-clinical Models
[ Time Frame: Weeks 4, 8, 12 and 26 ]

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. The number of viable graft cells were then compared to pre-clinical model data (i.e., control cell numbers) based on animal studies performed at ViaCyte (internal study report #SP-322).
2. Cohort 2: The Change in AUC (Area Under Curve) From Baseline to Week 26 in C-peptide During 4-hour MMTT
[ Time Frame: To Week 26 ]

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.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 65 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Men and non-pregnant women
  • Diagnosis of T1DM for a minimum of 3 years.
  • Stable, optimized diabetic regimen
  • Acceptable candidate for implant and explant procedures.
  • Willing and able to comply with protocol requirements.
  • Meet insulin dosing requirements per protocol

Exclusion Criteria:

• Advanced complications associated with diabetes
Open or close this module Contacts/Locations
Study Officials: Manasi Jaiman, MD
Principal Investigator
ViaCyte, Inc.
Locations: United States, California
AMCR Institute
Escondido, California, United States, 92025
Diablo Clinical Research
Walnut Creek, California, United States, 94598
United States, Georgia
Atlanta Diabetes Associates
Atlanta, Georgia, United States, 30318
United States, Texas
Texas Diabetes & Endocrinology
Austin, Texas, United States, 78731
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Citations:
Links:
Available IPD/Information:
Open or close this module Document Section
Study Protocol
Document Date: September 29, 2020
Uploaded: 03/28/2023 16:08
File Name: Prot_000.pdf
Statistical Analysis Plan
Document Date: March 15, 2021
Uploaded: 03/28/2023 16:31
File Name: SAP_001.pdf
Study Results
Open or close this module Participant Flow
Recruitment Details
Pre-assignment Details
 
Arm/Group Title 8 or 10 Sentinel Units Implanted (Cohort 1) 9 Dose Finding Units Implanted (Cohort 2)
Arm/Group Description 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.

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.
Period Title: Overall Study
Started 17 14
Completed 16 0
Not Completed 1 14
Reason Not Completed
Withdrawal by Subject 1 0
Lack of Efficacy 0 13
Safety Evaluation 0 1
Open or close this module Baseline Characteristics
Arm/Group TitleSentinel Units (Aka Cohort 1)Dose-finding Units (Aka Cohort 2)Total
Arm/Group Description

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

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 of all reporting groups
Overall Number of Baseline Participants 17 14 31
Baseline Analysis Population Description [Not Specified]
Age, Continuous
Mean (Standard Deviation)
Unit of measure: years
Number Analyzed17 Participants14 Participants31 Participants
37.0(13.11)44.1(8.53)40.2(11.7)
Sex: Female, Male
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed17 Participants14 Participants31 Participants
Female
10
58.82%
6
42.86%
16
51.61%
Male
7
41.18%
8
57.14%
15
48.39%
Ethnicity (NIH/OMB)
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed17 Participants14 Participants31 Participants
Hispanic or Latino
3
17.65%
0
0%
3
9.68%
Not Hispanic or Latino
14
82.35%
14
100%
28
90.32%
Unknown or Not Reported
0
0%
0
0%
0
0%
Region of Enrollment
Measure Type: Number
Unit of measure: participants
Number Analyzed17 Participants14 Participants31 Participants
United States
171431
Body Mass Index
Mean (Standard Deviation)
Unit of measure: kg/m^2
Number Analyzed17 Participants14 Participants31 Participants
24.98(2.992)27.28(2.807)26.00(3.09)
Duration of Type 1 Diabetes
Mean (Standard Deviation)
Unit of measure: years
Number Analyzed17 Participants14 Participants31 Participants
19.4(12.08)26.4(11.24)22.5(12.0)
Open or close this module Outcome Measures
1. Primary Outcome:
Title Cohort 1: The Percentage of Graft Cells Present at Post-implant Time Points Relative to Pre-clinical Models
Description 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. The number of viable graft cells were then compared to pre-clinical model data (i.e., control cell numbers) based on animal studies performed at ViaCyte (internal study report #SP-322).
Time Frame Weeks 4, 8, 12 and 26
Outcome Measure Data
Analysis Population Description
For each timepoint, explanted units from the 17 subjects were stained and evaluated for graft cells (note: not all subjects had units explanted at every timepoint)
   
Arm/Group TitleSentinel Units (Aka Cohort 1)
Arm/Group Description

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

Overall Number of Participants Analyzed17
Overall Number of Units Analyzed
Type of Units Analyzed: VC01-20 (-01)
71
Mean (Standard Deviation)
Unit of Measure: % cells in subjects vs. animal models
 
Week 4
Number Analyzed39 VC01-20 (-01)
18.88(14.43)
Week 8
Number Analyzed8 VC01-20 (-01)
6.23(4.63)
Week 12
Number Analyzed19 VC01-20 (-01)
7.38(7.77)
Week 26
Number Analyzed5 VC01-20 (-01)
8.02(8.09)

Quality Control Review Comment provided by the National Library of Medicine:

  1. The measure does not appear to include sufficient information to understand how outcomes are measured and reported.
2. Primary Outcome:
Title Cohort 2: The Change in AUC (Area Under Curve) From Baseline to Week 26 in C-peptide During 4-hour MMTT
Description 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.
Time Frame To Week 26
Outcome Measure Data
Analysis Population Description
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.
 
Arm/Group TitleDose-finding Units (Aka Cohort 2)
Arm/Group Description

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

Overall Number of Participants Analyzed1
Measure Type: Number
Unit of Measure: ng*h/mL
0.325
Open or close this module Adverse Events
 
Time Frame 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).
Adverse Event Reporting Description

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.

 
Arm/Group Title Sentinel Units (Aka Cohort 1) Dose-finding Units (Aka Cohort 2)
Arm/Group Description

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

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
All-Cause Mortality
  Sentinel Units (Aka Cohort 1)Dose-finding Units (Aka Cohort 2)
 Affected / At Risk (%)# Events Affected / At Risk (%)# Events
Total 0 / 17 (0%)0 / 14 (0%)
Serious Adverse Events
  Sentinel Units (Aka Cohort 1)Dose-finding Units (Aka Cohort 2)
 Affected / At Risk (%)# Events Affected / At Risk (%)# Events
Total 1 / 17 (5.88%)3 / 14 (21.43%)
Gastrointestinal disorders
Small Intestinal Obstruction † A 0 / 17 (0%)01 / 14 (7.14%)1
Metabolism and nutrition disorders
Hypoglycemia † A 0 / 17 (0%)01 / 14 (7.14%)1
Nervous system disorders
Subarachnoid hemorrhage † A 0 / 17 (0%)01 / 14 (7.14%)1
Pregnancy, puerperium and perinatal conditions
Vanishing Twin Syndrome † A 1 / 17 (5.88%)10 / 14 (0%)0
†Indicates events were collected by systematic assessment.
ATerm from vocabulary, MedDRA 22.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
  Sentinel Units (Aka Cohort 1)Dose-finding Units (Aka Cohort 2)
 Affected / At Risk (%)# Events Affected / At Risk (%)# Events
Total 17 / 17 (100%)14 / 14 (100%)
Blood and lymphatic system disorders
Anemia † A 1 / 17 (5.88%)11 / 14 (7.14%)1
Gastrointestinal disorders
Abdominal Pain † A 0 / 17 (0%)06 / 14 (42.86%)7
Constipation † A 1 / 17 (5.88%)13 / 14 (21.43%)3
Gastrooesophageal reflux disease † A 1 / 17 (5.88%)11 / 14 (7.14%)1
Nausea † A 4 / 17 (23.53%)53 / 14 (21.43%)6
Vomiting † A 4 / 17 (23.53%)52 / 14 (14.29%)2
General disorders
Complication of Device Removal † A 3 / 17 (17.65%)31 / 14 (7.14%)1
Fatigue † A 0 / 17 (0%)02 / 14 (14.29%)2
Implant Site Erythema † A 0 / 17 (0%)02 / 14 (14.29%)5
Implant Site Hypoaesthesia † A 2 / 17 (11.76%)20 / 14 (0%)0
Infusion Site Haemorrhage † A 2 / 17 (11.76%)20 / 14 (0%)0
Pyrexia † A 0 / 17 (0%)02 / 14 (14.29%)2
Infections and infestations
Postoperative wound infection † A 2 / 17 (11.76%)21 / 14 (7.14%)2
Injury, poisoning and procedural complications
Incision site complication † A 3 / 17 (17.65%)33 / 14 (21.43%)6
Incision site erythema † A 1 / 17 (5.88%)11 / 14 (7.14%)3
Incision site haematoma † A 2 / 17 (11.76%)20 / 14 (0%)0
Incision site haemorrhage † A 3 / 17 (17.65%)31 / 14 (7.14%)1
Incision site hypoaesthesia † A 0 / 17 (0%)02 / 14 (14.29%)4
Incision site pain † A 15 / 17 (88.24%)3012 / 14 (85.71%)60
Incision site pruritis † A 1 / 17 (5.88%)11 / 14 (7.14%)6
Incision site rash † A 1 / 17 (5.88%)11 / 14 (7.14%)1
Incision site swelling † A 2 / 17 (11.76%)32 / 14 (14.29%)2
Muscle strain † A 1 / 17 (5.88%)11 / 14 (7.14%)1
Post procedural complication † A 3 / 17 (17.65%)41 / 14 (7.14%)1
Post procedural contusion † A 1 / 17 (5.88%)17 / 14 (50%)12
Post procedural discomfort † A 1 / 17 (5.88%)25 / 14 (35.71%)6
Post procedural haematoma † A 2 / 17 (11.76%)31 / 14 (7.14%)1
Post procedural oedema † A 0 / 17 (0%)02 / 14 (14.29%)2
Post procedural swelling † A 0 / 17 (0%)04 / 14 (28.57%)8
Procedural nausea † A 2 / 17 (11.76%)22 / 14 (14.29%)2
Procedural pain † A 5 / 17 (29.41%)67 / 14 (50%)31
Seroma † A 0 / 17 (0%)04 / 14 (28.57%)10
Musculoskeletal and connective tissue disorders
Back pain † A 0 / 17 (0%)02 / 14 (14.29%)2
Nervous system disorders
Migraine † A 2 / 17 (11.76%)21 / 14 (7.14%)1
Tension headache † A 0 / 17 (0%)02 / 14 (14.29%)2
Psychiatric disorders
Anxiety † A 0 / 17 (0%)02 / 14 (14.29%)2
Depression † A 1 / 17 (5.88%)11 / 14 (7.14%)1
Respiratory, thoracic and mediastinal disorders
Dyspnoea † A 1 / 17 (5.88%)11 / 14 (7.14%)1
Skin and subcutaneous tissue disorders
Erythema † A 2 / 17 (11.76%)20 / 14 (0%)0
Rash † A 2 / 17 (11.76%)21 / 14 (7.14%)1
Vascular disorders
Hypertension † A 0 / 17 (0%)03 / 14 (21.43%)3
†Indicates events were collected by systematic assessment.
ATerm from vocabulary, MedDRA 22.0
Open or close this module Limitations and Caveats

Cohort 1 (Limitation): Graft cell viability relative to preclinical models determined on the first 5 patients in the trial only.

Cohort 2 (Limitation): Stimulated C-peptide data from the MMTT at Baseline and Week 26 showed undetectable C-peptide (<0.1 ng/mL) for all but one subject. For those subjects, AUC were not generated and assumed "zero" as serial undetectable C-peptide results cannot create a curve.
Open or close this module More Information
Certain Agreements:
Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between the Principal Investigator and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact:
Name/Official Title:
 Medical Information
Organization:
 Vertex
Phone:
 617-341-6777
Email:
 medicalinfo@vrtx.com
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