Back to results

Safety, Tolerability and Efficacy of Immunomodulation With AT-1501 in Islet Cell Transplantation

Primary Purpose

Type 1 Diabetes Mellitus

Status

Withdrawn

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

AT-1501

About this trial

This is an interventional treatment trial for Type 1 Diabetes Mellitus focused on measuring Type 1 Diabetes, T1D, Islet Cell Transplant, AT-1501, 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

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 intensive diabetes management 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 severe hypoglycemia
At least 2 unexplained SHEs not secondary to a missed meal or dosing error, etc., 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
Reduced awareness of hypoglycemia 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 transplant
HbA1c level less than 7% (53 mmol/mol)

Sites / Locations

University of Alberta

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AT-1501 Single Arm

Arm Description

Outcomes

Primary Outcome Measures

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

Incidence of adverse events

Efficacy- Insulin independence

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

Secondary Outcome Measures

Efficacy- Graft failure

Proportion of participants with graft failure

Efficacy- Durability of insulin independence- long term

Change in the proportion of participants that become insulin independent at year 2 and year 3

Efficacy- HbA1c

Proportion of participants with HbA1c <7.0% (53 mmol/mol) and free of serious hypoglycemic events (SHEs) Proportion of participants with HbA1c ≤6.5% (48 mmol/mol) and free from SHEs

Full Information

NCT ID

NCT04711226

First Posted

January 10, 2021

Last Updated

August 8, 2022

Sponsor

Anelixis Therapeutics, LLC

1. Study Identification

Unique Protocol Identification Number

NCT04711226

Brief Title

Safety, Tolerability and Efficacy of Immunomodulation With AT-1501 in Islet Cell Transplantation

Official Title

An Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of Immunomodulation With AT-1501 in Adults With Type 1 Diabetes Undergoing Islet Cell Transplant

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Withdrawn

Why Stopped

No participants enrolled

Study Start Date

February 19, 2021 (Actual)

Primary Completion Date

June 2024 (Anticipated)

Study Completion Date

June 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Anelixis Therapeutics, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

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 AT-1501 in an immunomodulation regimen in adult patients with T1D undergoing an islet cell transplant. This study will also provide valuable data with respect to its potential additional uses in autoimmunity and solid organ transplant. This is a single arm open-label study and up to 6 participants will be recruited at a single center in Canada. The objectives include: To assess the safety and tolerability of 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 immunomodulation with AT-1501 in adults with T1D undergoing islet cell transplant. The duration of treatment may vary from participant to participant and could be up to 20 months. 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

Type 1 Diabetes Mellitus

Keywords

Type 1 Diabetes, T1D, Islet Cell Transplant, AT-1501, 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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AT-1501 Single Arm

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

AT-1501

Intervention Description

AT-1501 IV infusion

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 1 year post transplant for approximately 2 years

Title

Efficacy- Insulin independence

Description

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

Time Frame

Days 75 , Day 365 post-first transplant, and final transplant and 1 year after discontinuation of AT-1501

Secondary Outcome Measure Information:

Title

Efficacy- Graft failure

Description

Proportion of participants with graft failure

Time Frame

Day 365

Title

Efficacy- Durability of insulin independence- long term

Description

Change in 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

Title

Efficacy- HbA1c

Description

Proportion of participants with HbA1c <7.0% (53 mmol/mol) and free of serious hypoglycemic events (SHEs) Proportion of participants with HbA1c ≤6.5% (48 mmol/mol) and free from SHEs

Time Frame

Day 365 and free of serious hypoglycemic events from Day 28 to 365 post-first transplant

Other Pre-specified Outcome Measures:

Title

Exploratory- Hypoglycemia unawareness (using the method of Clarke)

Description

Proportion of participants with hypoglycemia unawareness

Time Frame

Day 75, 365, and 1, 2 and 3 years after discontinuation of AT-1501

Title

Exploratory- Glycemic lability (using CGMS)

Description

Change in glycemic lability using CGMS- Continuous Glucose Monitoring System

Time Frame

Day 75, 365, and 1, 2 and 3 years after discontinuation of AT-1501

Title

Exploratory- Glycemic variability (using CGMS)

Description

Change in glycemic variability using CGMS- Continuous Glucose Monitoring System

Time Frame

Day 75, 365, and 1, 2 and 3 years after discontinuation of AT-1501

Title

Exploratory- Albumin excretion ratio (AER)

Description

Change in albumin excretion ratio (AER)

Time Frame

Day 365 post-first, and final transplant

Title

Exploratory- eGRF

Description

Change in eGRF

Time Frame

Day 365 post-first, and final transplant

Title

Exploratory- Macroalbuminemia

Description

Change in percent new macroalbuminemia

Time Frame

Day 365 post-first, and final transplant

Title

Exploratory- biomarkers of tissue damage and inflammation

Description

Biomarkers

Time Frame

Day -2, 3, 14, 28, 75, 175, 364

Title

Exploratory -Pharmacokinetic Parameters-AUC

Description