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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: AT-1501

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2E1
      • University of Alberta

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men and women 18-65 years of age
2. A diagnosis of T1D ≥5 years with onset of disease at <40 years of age
3. 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
4. At least 2 unexplained SHEs not secondary to a missed meal or dosing error, etc., in the 12 months prior to Screening
5. Glycosylated hemoglobin (HbA1c) level greater than 7% (53 mmol/mol) and less than 9.5% (80 mmol/mol) inclusive
6. 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
7. 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:

1. Any previous transplant
2. HbA1c level less than 7% (53 mmol/mol)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AT-1501 Single Arm	Drug: AT-1501; AT-1501 IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety- Adverse Events (AE) and Adverse Events of Special Interest (AEoSI)	Incidence of adverse events	Accessed from date of transplant through 1 year post transplant for approximately 2 years
Efficacy- Insulin independence	Change in the proportion of participants that become insulin independent at Days 75 and 365 post-first, and final transplant	Days 75 , Day 365 post-first transplant, and final transplant and 1 year after discontinuation of AT-1501

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy- Graft failure	Proportion of participants with graft failure	Day 365
Efficacy- Durability of insulin independence- long term	Change in the proportion of participants that become insulin independent at year 2 and year 3	2 and 3 years after discontinuation of AT- 1501
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	Day 365 and free of serious hypoglycemic events from Day 28 to 365 post-first transplant

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory- Hypoglycemia unawareness (using the method of Clarke)	Proportion of participants with hypoglycemia unawareness	Day 75, 365, and 1, 2 and 3 years after discontinuation of AT-1501
Exploratory- Glycemic lability (using CGMS)	Change in glycemic lability using CGMS- Continuous Glucose Monitoring System	Day 75, 365, and 1, 2 and 3 years after discontinuation of AT-1501
Exploratory- Glycemic variability (using CGMS)	Change in glycemic variability using CGMS- Continuous Glucose Monitoring System	Day 75, 365, and 1, 2 and 3 years after discontinuation of AT-1501
Exploratory- Albumin excretion ratio (AER)	Change in albumin excretion ratio (AER)	Day 365 post-first, and final transplant
Exploratory- eGRF	Change in eGRF	Day 365 post-first, and final transplant
Exploratory- Macroalbuminemia	Change in percent new macroalbuminemia	Day 365 post-first, and final transplant
Exploratory- biomarkers of tissue damage and inflammation	Biomarkers	Day -2, 3, 14, 28, 75, 175, 364
Exploratory -Pharmacokinetic Parameters-AUC	Pharmacokinetics (PK) of AT-1501	T=0 (pre infusion), 1 (end of infusion), 2, 4, 8, 12, 24 and 48 hrs.
Exploratory- Pharmacokinetic Parameters-Cmax	Pharmacokinetics (PK) of AT-1501	T=0 (pre infusion), 1 (end of infusion), 2, 4, 8, 12, 24 and 48 hrs.
Exploratory- Pharmacokinetic Parameters-CL	Pharmacokinetics (PK) of AT-1501	T=0 (pre infusion), 1 (end of infusion), 2, 4, 8, 12, 24 and 48 hrs.
Exploratory- Pharmacokinetic Parameters- Vdss	Pharmacokinetics (PK) of AT-1501	T=0 (pre infusion), 1 (end of infusion), 2, 4, 8, 12, 24 and 48 hrs.
Exploratory- Pharmacokinetic Parameters- (t1/2)	Pharmacokinetics (PK) of AT-1501	T=0 (pre infusion), 1 (end of infusion), 2, 4, 8, 12, 24 and 48 hrs.

Collaborators and Investigators

• Sponsor: Anelixis Therapeutics, LLC
• Investigators: Study Chair: Jeff Bornstein, MD, Eledon Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2021
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): June 1, 2026

Study Registration Dates

• First Submitted: January 10, 2021
• First Submitted That Met QC Criteria: January 12, 2021
• First Posted (Actual): January 15, 2021

Study Record Updates

• Last Update Posted (Actual): August 10, 2022
• Last Update Submitted That Met QC Criteria: August 8, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Hypoglycemia; Immune System Diseases; monoclonal antibody; Hyperglycemia; Autoimmune Diseases; Type 1 Diabetes; T1D; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus, Type 1; AT-1501; CD40L inhibitor; Islet Cell Transplant; humanized blocking antibody to CD40L; Glucose Metabolism Diseases; Graft
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: AT-1501-I203 (Other Identifier: Anelixis)

Drug and device information, study documents

• 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