PolyTreg Immunotherapy in Islet Transplantation

Summary

Islet transplantation is a relatively new procedure used in people with difficult to control Type 1 diabetes. Patients who receive an islet transplant take medication that suppresses their immune system and prevent rejection of the islet tissue. In spite of the strengths of the current immunosuppression regimen, it has failed to enhance single-donor success rates, and the majority of patients require 2 or more islet transplants to achieve insulin independence. The need for life-long, high-dose immunosuppression is also associated with substantial side effects, and continues to limit application of islet transplantation earlier in the course of the disease.

The investigators have learned that Regulatory T cells (Tregs), a small subset of cluster of differentiation 4+ (CD4+) T cells, have emerged as the major contributor to self-tolerance through suppression of activation and effector function of other immune cells. Tregs function by preventing the initiation of unwanted immune activation and by suppressing ongoing immune response to limit bystander tissue destruction. It has been suggested that infusion of Tregs before extensive graft damage may improve long-term graft outcomes.

This study is an open label, controlled, dose finding pilot study. Up to 18 participants will be recruited including 12 participants receiving the investigational treatment and 6 participants being assigned to control group. All participants will undergo the routine Standard of Care islet transplant procedure, and will be maintained on lower dose tacrolimus and sirolimus immunosuppression.

The primary goal is to assess the safety and feasibility of intravenous infusion of ex vivo-selected and ex vivo-expanded autologous PolyTregs in islet transplant patients. The other goal is to assess the effect of Tregs on beta cell function in islet transplant patients.

The control group (6) will receive the current Edmonton islet transplant induction therapy (Alemtuzumab with Etanercept and Anakinra). The intervention group (up to 12) will receive islet transplant with same induction therapy as control group and PolyTregs (400-1600 million) six weeks post- transplant and will be followed for 1 year to assess safety and preliminary efficacy of Treg therapy. The Treg product will be administered via a peripheral intravenous (IV) line primed with saline per established standard operating procedures in approximately 20 to 30 minutes. The intravenous line will be maintained after the infusion and the participant will be asked to remain in the hospital for 24 hours. All participants will be maintained on low dose tacrolimus and sirolimus immunosuppression.

The investigators will also use retrospective data from the islet transplant cohort receiving Tac/mycophenolate mofetil(MMF) with alemtuzumab (\>100 patients).

All study participants will be followed up for 58 weeks. Tests and assessments will be performed at each key study visit and will be allowed for +/- 2 weeks to accommodate scheduling.

The following measurements will be recorded at each key study visit :

Blood work, including the following:

Complete blood count (CBC) and differential

Creatinine and electrolytes

Fasting glucose and c-peptide

Any adverse events

Physical examination

Body weight (kg)

Vital signs (BP, HR)

Glucose records for self-monitoring.

Hemoglobin A1c

Insulin use (total daily dose)

Autoantibodies and autoreactive T cell

MMTT

Immune profile

Conditions

• Diabetes
• Diabetes Mellitus, Type 1

Interventions

BIOLOGICAL

PolyTregs

Treatment group receive PolyTregs 6 weeks after islet transplantation as immunotherapy to improve islet survival and reduce the need for immunosuppression drugs.

Sponsors & Collaborators

• Diabetes Research Institute Foundation

  collaborator OTHER

• Liana's Dream Foundation

  collaborator UNKNOWN

• Juvenile Diabetes Research Foundation

  collaborator OTHER

• Alberta Diabetes Institute

  collaborator OTHER

• University of Alberta

  lead OTHER

Principal Investigators

• James Shapiro, MD, PhD · University of Alberta

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

68 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-02-01

Primary Completion

2024-08-12

Completion

2024-12-17

FDA Drug

Yes

Countries

• Canada

Study Locations