Safety, Tolerability, and Efficacy of Immunomodulation With AT-1501 in Combination With Transplanted Islet Cells in Adults With Brittle T1D
- Conditions
- Brittle Type 1 Diabetes Mellitus
- Interventions
- Biological: AT-1501 IV InfusionBiological: Isolated cadaveric islet cells
- Registration Number
- NCT05480657
- Lead Sponsor
- Eledon Pharmaceuticals
- 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 transplantation of experimental islet cells as a potential treatment for brittle type 1 diabetes mellitus. It will also assess the safety, tolerability and efficacy of AT-1501 in an immunomodulation regimen in adult patients with brittle T1D undergoing an islet cell transplant. This is a single arm open-label study and up to 6 participants will be recruited at a single center in the United States.
The objectives include:
* To assess the safety and tolerability of transplanted islet cells and 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 transplanted islet cells and immunomodulation with AT-1501 in adults with brittle T1D undergoing islet cell transplant.
The duration of treatment may vary from participant to participant and could be up to 2 years. Participants may receive up to 2 islet cell transplants.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- 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 appropriate diabetes management in accordance with the standard of care, 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 unexplained SHEs
- At least 3 unexplained SHEs not secondary to a missed meal or dosing error, 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
- Impaired awareness of hypoglycemia (IAH) 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
- Any previous solid organ or islet allotransplant
- Body mass index (BMI) >30 kg/m2
- Insulin requirement >1.0 unit/kg/day or <15 units/day
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Single Arm AT-1501 Isolated cadaveric islet cells Single-arm, open-label trial Single Arm AT-1501 AT-1501 IV Infusion Single-arm, open-label trial
- Primary Outcome Measures
Name Time Method Efficacy - Insulin independence Date of transplant through Day 364 post- final transplant The proportion of participants that become insulin independent at Days 75 and 365 post-first, and final transplant
Safety - Adverse Events (AE) and Adverse Events of Special Interest (AEoSI) Accessed from date of transplant through Day 364 post final transplant for approximately 2 years Incidence of adverse events
- Secondary Outcome Measures
Name Time Method Efficacy - Graft failure Proportion of participants with graft failure at Day 364 post final transplant Date of transplant through Day 364 post final transplant
Efficacy - HbA1c Date of transplant through Day 364 post-final transplant Proportion of participants with HbA1c \<7.0% (53 mmol/mol) and free of serious hypoglycemic events (SHEs) from Day 28 to Day 364 post first and final transplant.
Efficacy - Durability of insulin independence - long term 2 and 3 years after discontinuation of AT- 1501 The proportion of participants that become insulin independent at year 2 and year 3
Efficacy - Durability of insulin independence Date of transplant through Day 364 post final transplant The proportion of participants that become insulin independent at Day 364 post-transplant
Trial Locations
- Locations (1)
University of Chicago
🇺🇸Chicago, Illinois, United States