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

Type 1 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04711226
• Other study ID #: AT-1501-I203
• Secondary ID: AT-1501-I203
• Status: Withdrawn
• Phase: Phase 2
• Start date: February 19, 2021
• Est. completion date: June 2026

Study information

• Verified date: August 2022
• Source: Eledon Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2026
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Drug:
• AT-1501
AT-1501 IV infusion

Locations

Country	Name	City	State
Canada	University of Alberta	Edmonton	Alberta

Sponsors (1)

Lead Sponsor	Collaborator
Anelixis Therapeutics, LLC

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	Exploratory- Albumin excretion ratio (AER)	Change in albumin excretion ratio (AER)	Day 365 post-first, and final transplant
Other	Exploratory- eGRF	Change in eGRF	Day 365 post-first, and final transplant
Other	Exploratory- Macroalbuminemia	Change in percent new macroalbuminemia	Day 365 post-first, and final transplant
Other	Exploratory- biomarkers of tissue damage and inflammation	Biomarkers	Day -2, 3, 14, 28, 75, 175, 364
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Primary	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
Primary	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	Efficacy- Graft failure	Proportion of participants with graft failure	Day 365
Secondary	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
Secondary	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