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Withdrawn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
Sponsored by
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
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
No
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
Pharmacokinetics (PK) of AT-1501
Time Frame
T=0 (pre infusion), 1 (end of infusion), 2, 4, 8, 12, 24 and 48 hrs.
Title
Exploratory- Pharmacokinetic Parameters-Cmax
Description
Pharmacokinetics (PK) of AT-1501
Time Frame
T=0 (pre infusion), 1 (end of infusion), 2, 4, 8, 12, 24 and 48 hrs.
Title
Exploratory- Pharmacokinetic Parameters-CL
Description
Pharmacokinetics (PK) of AT-1501
Time Frame
T=0 (pre infusion), 1 (end of infusion), 2, 4, 8, 12, 24 and 48 hrs.
Title
Exploratory- Pharmacokinetic Parameters- Vdss
Description
Pharmacokinetics (PK) of AT-1501
Time Frame
T=0 (pre infusion), 1 (end of infusion), 2, 4, 8, 12, 24 and 48 hrs.
Title
Exploratory- Pharmacokinetic Parameters- (t1/2)
Description
Pharmacokinetics (PK) of AT-1501
Time Frame
T=0 (pre infusion), 1 (end of infusion), 2, 4, 8, 12, 24 and 48 hrs.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeff Bornstein, MD
Organizational Affiliation
Eledon Pharmaceuticals
Official's Role
Study Chair
Facility Information:
Facility Name
University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2E1
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
Safety, Tolerability and Efficacy of Immunomodulation With AT-1501 in Islet Cell Transplantation
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