An Open-Label, FIH Study Evaluating the Safety, Tolerability, and Efficacy of VCTX211 Combination Product in Subjects With T1D

Study Overview
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Brief Summary
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This is an open-label, multicenter, Phase 1/2 study evaluating the Safety, Tolerability, and Efficacy of VCTX211 Combination Product in Subjects with T1D

Detailed Description
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VCTX211 combination product (unit) compromises 2 components: (1) allogeneic pancreatic endoderm cells (PEC211) genetically modified using Cluster 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 PEC211 cells.

Official Title
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An Open-Label, First-in-Human Study Evaluating the Safety, Tolerability, and Efficacy of VCTX211 Combination Product in Subjects With Type 1 Diabetes Mellitus (T1D)

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

Intervention / Treatment
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* Combination Product: VCTX211


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of T1D for a minimum of 5 years Stable diabetes 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
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VCTX211 unit<br> | Combination Product: VCTX211<br>* CRISPR-Cas9 genetically modified PEC211 cells loaded into a delivery device<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events with causality related to VCTX211 units, the surgical procedures and/or medical interventions required to implant and explant the VCTX211 units. |  | From implantation up to 12 months post implantation | 
| Assess the clinical efficacy of VCTX211 units via evaluation of C-peptide increase from the baseline. |  | From implantation up to 12 months post implantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events reported in patients implanted with VCTX211 units. |  | From implantation up to 12 months post implantation | 
| Assess the clinical efficacy of VCTX211 units via evaluation of changes in exogenous insulin use from baseline. |  | From implantation up to 12 months post implantation | 
| Assess the clinical efficacy of VCTX211 units via evaluation of changes in number of hypoglycemic evens from baseline. |  | From implantation up to 12 months post implantation | 
| Assess the clinical efficacy of VCTX211 units via evaluation of changes in hemoglobin A1C levels from baseline. |  | From implantation up to 12 months post implantation | 
| Assess the clinical efficacy of VCTX211 units via evaluation of percentage of time in pre-defined glycemic ranges, as measured by a continuous glucose monitor, from baseline. |  | From implantation up to 12 months post implantation | 
| Qualitative evaluation of immune response to VCTX211 units assessed by histological staining for markers of host adaptive immune cells within the graft. |  | From implantation up to 12 months post implantation | 
| Incidence of new alloreactive antibodies found in the blood of patients post implantation. |  | From implantation up to 12 months post implantation | 
| Incidence of new autoreactive antibodies found in the blood of patients post implantation. |  | From implantation up to 12 months post implantation | 
| The percentage of viable graft cells per unit using immunohistochemical staining. |  | From implantation up to 12 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 12 months post implantation | 

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