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

Primary Purpose

Brittle Type 1 Diabetes Mellitus

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

AT-1501 IV Infusion

Isolated cadaveric islet cells

About this trial

This is an interventional treatment trial for Brittle Type 1 Diabetes Mellitus focused on measuring AT-1501, Type 1 Diabetes, T1D, Islet Cell Transplant, humanized blocking antibody to CD40L, CD40L inhibitor, monoclonal antibody, Glucose Metabolism Diseases, Diabetes Mellitus, Type 1, Endocrine System Diseases, Graft, Metabolic Diseases, Immune System Diseases, Autoimmune Diseases, Hypoglycemia, Hyperglycemia, Brittle T1D, Brittle Type 1 Diabetes

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept 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

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

Sites / Locations

University of Chicago

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single Arm AT-1501

Arm Description

Single-arm, open-label trial

Outcomes

Primary Outcome Measures

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

Incidence of adverse events

Efficacy - Insulin independence

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

Secondary Outcome Measures

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.

Efficacy - Graft failure

Date of transplant through Day 364 post final transplant

Efficacy - Durability of insulin independence

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

Efficacy - Durability of insulin independence - long term

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

Full Information

NCT ID

NCT05480657

First Posted

July 27, 2022

Last Updated

January 13, 2023

Sponsor

Eledon Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT05480657

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Withdrawn

Why Stopped

Study withdrawn

Study Start Date

September 30, 2022 (Actual)

Primary Completion Date

August 2024 (Anticipated)

Study Completion Date

August 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eledon Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Brittle Type 1 Diabetes Mellitus

Keywords

AT-1501, Type 1 Diabetes, T1D, Islet Cell Transplant, humanized blocking antibody to CD40L, CD40L inhibitor, monoclonal antibody, Glucose Metabolism Diseases, Diabetes Mellitus, Type 1, Endocrine System Diseases, Graft, Metabolic Diseases, Immune System Diseases, Autoimmune Diseases, Hypoglycemia, Hyperglycemia, Brittle T1D, Brittle Type 1 Diabetes

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Model Description

Single-arm, open-label trial

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Single Arm AT-1501

Arm Type

Experimental

Arm Description

Single-arm, open-label trial

Intervention Type

Biological

Intervention Name(s)

AT-1501 IV Infusion

Intervention Description

Investigational study drug

Intervention Type

Biological

Intervention Name(s)

Isolated cadaveric islet cells

Intervention Description

Infusion of human cadaveric islet cells into the portal vein

Primary Outcome Measure Information:

Title

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

Description

Incidence of adverse events

Time Frame

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

Title

Efficacy - Insulin independence

Description

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 Outcome Measure Information:

Title

Efficacy - HbA1c

Description

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

Title

Efficacy - Graft failure

Description

Date of transplant through Day 364 post final transplant

Time Frame

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

Title

Efficacy - Durability of insulin independence

Description

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

Time Frame

Date of transplant through Day 364 post final transplant

Title

Efficacy - Durability of insulin independence - long term

Description

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jeff Bornstein, MD

Organizational Affiliation

Eledon Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

University of Chicago

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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