Safety, Tolerability, and Efficacy of Immunomodulation With AT-1501 in Combination With Transplanted Islet Cells in Adults With Brittle T1D

Eledon Pharmaceuticals

Overview

This study will evaluate the safety, tolerability and efficacy of AT-1501 in an immunomodulation regimen in adult patients with T1D undergoing an islet cell transplant.

This study will evaluate the safety, tolerability and efficacy of transplantation of experimental islet cells as a potential treatment for brittle type 1 diabetes mellitus. It will also assess the safety, tolerability and efficacy of AT-1501 in an immunomodulation regimen in adult patients with brittle T1D undergoing an islet cell transplant. This is a single arm open-label study and up to 6 participants will be recruited at a single center in the United States. The objectives include: * To assess the safety and tolerability of transplanted islet cells and immunomodulation with AT-1501, in combination (AT+) with rabbit anti-thymoglobulin (ATG), etanercept and mycophenolate mofetil (MMF/EC-MPS) in adults with T1D undergoing islet cell transplant. * To assess the efficacy of transplanted islet cells and immunomodulation with AT-1501 in adults with brittle T1D undergoing islet cell transplant. The duration of treatment may vary from participant to participant and could be up to 2 years. Participants may receive up to 2 islet cell transplants.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Conditions

Brittle Type 1 Diabetes Mellitus

Interventions

AT-1501 IV InfusionBIOLOGICAL

Investigational study drug

Isolated cadaveric islet cellsBIOLOGICAL

Infusion of human cadaveric islet cells into the portal vein

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Men and women 18-65 years of age * A diagnosis of T1D ≥5 years with onset of disease at \<40 years of age * Involvement in appropriate diabetes management in accordance with the standard of care, as directed by an endocrinologist or diabetologist with at least 3 clinical evaluations within the 12 months prior to Screening; using an insulin pump or multiple daily injection (MDI) insulin therapy; and, unable to achieve acceptable metabolic control because of the occurrence of unexplained SHEs * At least 3 unexplained SHEs not secondary to a missed meal or dosing error, in the 12 months prior to Screening * Glycosylated hemoglobin (HbA1c) level greater than 7% (53 mmol/mol) and less than 9.5% (80 mmol/mol) inclusive * Absence of stimulated C peptide (\< 0.3 ng/mL) in response to a mixed meal tolerance test (MMTT) measured at 60 and 90 minutes after the start of consumption * Impaired awareness of hypoglycemia (IAH) as defined by a Clarke Score \[Clarke 1995\] of 4 or more at the time of Screening, during the Screening period, and within the last 6 months prior to the transplant Exclusion Criteria: * Any previous solid organ or islet allotransplant * Body mass index (BMI) \>30 kg/m2 * Insulin requirement \>1.0 unit/kg/day or \<15 units/day

Locations (1)

University of Chicago

Chicago, Illinois, United States

Outcomes

Primary Outcomes

Safety - Adverse Events (AE) and Adverse Events of Special Interest (AEoSI)

Incidence of adverse events

Time frame: Accessed from date of transplant through Day 364 post final transplant for approximately 2 years

Efficacy - Insulin independence

The proportion of participants that become insulin independent at Days 75 and 365 post-first, and final transplant

Time frame: Date of transplant through Day 364 post- final transplant

Secondary Outcomes

Efficacy - HbA1c

Proportion of participants with HbA1c \<7.0% (53 mmol/mol) and free of serious hypoglycemic events (SHEs) from Day 28 to Day 364 post first and final transplant.

Time frame: Date of transplant through Day 364 post-final transplant

Efficacy - Graft failure

Date of transplant through Day 364 post final transplant

Time frame: Proportion of participants with graft failure at Day 364 post final transplant

Efficacy - Durability of insulin independence

The proportion of participants that become insulin independent at Day 364 post-transplant

Time frame: Date of transplant through Day 364 post final transplant

Efficacy - Durability of insulin independence - long term

The proportion of participants that become insulin independent at year 2 and year 3

Time frame: 2 and 3 years after discontinuation of AT- 1501

Data from ClinicalTrials.gov

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