An Open-Label, FIH Study Evaluating the Safety and Tolerability of VCTX210A Combination Product in Subjects With T1D

Study Overview
=================
Brief Summary
-----------------
This is an open-label, multicenter, Phase 1 study evaluating the safety and tolerability of VCTX210A combination product in patients with T1D

Detailed Description
-----------------
VCTX210A combination product (unit) comprises 2 components: (1) allogeneic pancreatic endoderm cells (PEC210A) genetically modified using Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9 (CRISPR/Cas9) to promote immune evasiveness and survival, and (2) a durable, removable, perforated device designed to deliver and retain the PEC210A cells.

Official Title
-----------------
An Open-Label, First-In-Human Study Evaluating the Safety and Tolerability of VCTX210A Combination Product in Subjects With Type 1 Diabetes Mellitus (T1D)

Conditions
-----------------
Diabetes Mellitus, Diabetes Mellitus, Type 1, Glucose Metabolism Disorders, Metabolic Disease, Endocrine System Diseases, Autoimmune Diseases, Immune System Diseases

Intervention / Treatment
-----------------
* Combination Product: VCTX210A unit


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Diagnosis of T1D for a minimum of 5 years Stable, optimized diabetic regimen for at least 3 months prior to enrollment Exclusion Criteria Medical history of islet cell, kidney, and/or pancreas transplant Occurrence of 2 or more severe, unexplained hypoglycemic events within 6 months prior to enrollment Known causes of diabetes other than T1D Immunosuppressant therapy in the previous 30 days and/or requirements for chronic immunosuppressive therapy during the study Prior treatment with gene therapy or edited product

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VCTX210A combination product<br>Up to seven (7) units will be implanted | Combination Product: VCTX210A unit<br>* CRISPR-Cas9 genetically modified PEC210A cells loaded into a delivery device<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events with causality related to VCTX210A units and/or the surgical procedures required to implant and explant the VCTX210A units. |  | From implantation up to 6 months post implantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Qualitative evaluation of immune response to VCTX210A units assessed by histological staining for markers of host innate immune cells within the graft. |  | From implantation up to 6 months post implantation | 
| Qualitative evaluation of immune response to VCTX210A units assessed by histological staining for markers of host adaptive immune cells within the graft. |  | From implantation up to 6 months post implantation | 
| Incidence of new alloreactive antibodies found in the blood of patients post implantation. |  | From implantation up to 6 months post implantation | 
| Incidence of new autoreactive antibodies found in the blood of patients post implantation. |  | From implantation up to 6 months post implantation | 
| The percentage of viable graft cells per unit using immunohistochemical staining. |  | From implantation up to 6 months post implantation | 
| The percentage of graft cells per unit that have differentiated into endocrine/beta cells as determined by immunohistochemical staining. |  | From implantation up to 6 months post implantation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
T1D, Type 1 Diabetes, Allogeneic, Combination Device, CRISPR-Cas9, Cell Therapy, T1DM, Diabetes, VCTX