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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: AT-1501


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AT-1501 Single Arm<br> | Drug: AT-1501<br>* AT-1501 IV infusion<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Graft, 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, Metabolic Diseases, Immune System Diseases, Autoimmune Diseases, Hypoglycemia, Hyperglycemia