Clinical trial NCT05480657: Safety, Tolerability, and Efficacy of Immunomodulation With AT-1501 in Combination With Transplanted Islet Cells in Adults With Brittle T1D
Official title: AT-1501-I206: An Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of Transplanted Islet Cells and AT-1501 Immunomodulation in Adults With Brittle Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Brittle Type 1 Diabetes Mellitus
Keywords: 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
Graft
Metabolic Diseases
Immune System Diseases
Autoimmune Diseases
Hypoglycemia
Hyperglycemia
Brittle T1D
Brittle Type 1 Diabetes
Lead sponsor: Eledon Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2022-07-29
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single-arm, open-label trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Safety - Adverse Events (AE) and Adverse Events of Special Interest (AEoSI)
timeFrame: Accessed from date of transplant through Day 364 post final transplant for approximately 2 years
measure: Efficacy - Insulin independence
timeFrame: Date of transplant through Day 364 post- final transplant
Secondary outcomes:
measure: Efficacy - HbA1c
timeFrame: Date of transplant through Day 364 post-final transplant
measure: Efficacy - Graft failure
timeFrame: Proportion of participants with graft failure at Day 364 post final transplant
measure: Efficacy - Durability of insulin independence
timeFrame: Date of transplant through Day 364 post final transplant
measure: Efficacy - Durability of insulin independence - long term
timeFrame: 2 and 3 years after discontinuation of AT- 1501
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
Study officials:
affiliation: Eledon Pharmaceuticals
name: Jeff Bornstein, MD
role: STUDY_DIRECTOR
References: