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

Sponsor

Eledon Pharmaceuticals (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05480657

Collaborator

(none)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Brittle Type 1 Diabetes Mellitus	Biological: AT-1501 IV Infusion Biological: Isolated cadaveric islet cells	Phase 1/Phase 2

Detailed Description

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 Design

Study Type:

Interventional

Anticipated Enrollment :

6 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Single-arm, open-label trialSingle-arm, open-label trial

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

AT-1501-I206: An Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of Transplanted Islet Cells and AT-1501 Immunomodulation in Adults With Brittle Type 1 Diabetes

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Aug 1, 2024

Anticipated Study Completion Date :

Aug 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single Arm AT-1501 Single-arm, open-label trial	Biological: AT-1501 IV Infusion Investigational study drug Biological: Isolated cadaveric islet cells Infusion of human cadaveric islet cells into the portal vein

Arm

Intervention/Treatment

Experimental: Single Arm AT-1501

Single-arm, open-label trial

Biological: AT-1501 IV Infusion

Investigational study drug

Biological: Isolated cadaveric islet cells

Infusion of human cadaveric islet cells into the portal vein

Outcome Measures

Primary Outcome Measures

Safety - Adverse Events (AE) and Adverse Events of Special Interest (AEoSI) [Accessed from date of transplant through Day 364 post final transplant for approximately 2 years]
Incidence of adverse events
Efficacy - Insulin independence [Date of transplant through Day 364 post- final transplant]
The proportion of participants that become insulin independent at Days 75 and 365 post-first, and final transplant

Secondary Outcome Measures

Efficacy - HbA1c [Date of transplant through Day 364 post-final transplant]
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.
Efficacy - Graft failure [Proportion of participants with graft failure at Day 364 post final transplant]
Date of transplant through Day 364 post final transplant
Efficacy - Durability of insulin independence [Date of transplant through Day 364 post final transplant]
The proportion of participants that become insulin independent at Day 364 post-transplant
Efficacy - Durability of insulin independence - long term [2 and 3 years after discontinuation of AT- 1501]
The proportion of participants that become insulin independent at year 2 and year 3

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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