Type 1 Diabetes Mellitus
Conditions
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
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.
Interventions
DRUGAT-1501
AT-1501 IV infusion
Sponsors
Anelixis Therapeutics, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety- Adverse Events (AE) and Adverse Events of Special Interest (AEoSI) | Accessed from date of transplant through 1 year post transplant for approximately 2 years | Incidence of adverse events |
| Efficacy- Insulin independence | Days 75 , Day 365 post-first transplant, and final transplant and 1 year after discontinuation of AT-1501 | Change in the proportion of participants that become insulin independent at Days 75 and 365 post-first, and final transplant |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy- Graft failure | Day 365 | Proportion of participants with graft failure |
| Efficacy- Durability of insulin independence- long term | 2 and 3 years after discontinuation of AT- 1501 | Change in the proportion of participants that become insulin independent at year 2 and year 3 |
| Efficacy- HbA1c | Day 365 and free of serious hypoglycemic events from Day 28 to 365 post-first transplant | * 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory- Macroalbuminemia | Day 365 post-first, and final transplant | Change in percent new macroalbuminemia |
| Exploratory- biomarkers of tissue damage and inflammation | Day -2, 3, 14, 28, 75, 175, 364 | Biomarkers |
| Exploratory -Pharmacokinetic Parameters-AUC | T=0 (pre infusion), 1 (end of infusion), 2, 4, 8, 12, 24 and 48 hrs. | Pharmacokinetics (PK) of AT-1501 |
| Exploratory- Hypoglycemia unawareness (using the method of Clarke) | Day 75, 365, and 1, 2 and 3 years after discontinuation of AT-1501 | Proportion of participants with hypoglycemia unawareness |
| Exploratory- Pharmacokinetic Parameters-CL | T=0 (pre infusion), 1 (end of infusion), 2, 4, 8, 12, 24 and 48 hrs. | Pharmacokinetics (PK) of AT-1501 |
| Exploratory- Pharmacokinetic Parameters- Vdss | T=0 (pre infusion), 1 (end of infusion), 2, 4, 8, 12, 24 and 48 hrs. | Pharmacokinetics (PK) of AT-1501 |
| Exploratory- Pharmacokinetic Parameters- (t1/2) | T=0 (pre infusion), 1 (end of infusion), 2, 4, 8, 12, 24 and 48 hrs. | Pharmacokinetics (PK) of AT-1501 |
| Exploratory- Pharmacokinetic Parameters-Cmax | T=0 (pre infusion), 1 (end of infusion), 2, 4, 8, 12, 24 and 48 hrs. | Pharmacokinetics (PK) of AT-1501 |
| Exploratory- Glycemic lability (using CGMS) | Day 75, 365, and 1, 2 and 3 years after discontinuation of AT-1501 | Change in glycemic lability using CGMS- Continuous Glucose Monitoring System |
| Exploratory- Glycemic variability (using CGMS) | Day 75, 365, and 1, 2 and 3 years after discontinuation of AT-1501 | Change in glycemic variability using CGMS- Continuous Glucose Monitoring System |
| Exploratory- Albumin excretion ratio (AER) | Day 365 post-first, and final transplant | Change in albumin excretion ratio (AER) |
| Exploratory- eGRF | Day 365 post-first, and final transplant | Change in eGRF |
Countries
Canada
Outcome results
None listed