Clinical trial NCT04711226: Safety, Tolerability and Efficacy of Immunomodulation With AT-1501 in Islet Cell Transplantation
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Type 1 Diabetes Mellitus
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
Lead sponsor: Eledon Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-01-15
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
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 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Safety- Adverse Events (AE) and Adverse Events of Special Interest (AEoSI)
timeFrame: Accessed from date of transplant through 1 year post transplant for approximately 2 years
measure: Efficacy- Insulin independence
timeFrame: Days 75 , Day 365 post-first transplant, and final transplant and 1 year after discontinuation of AT-1501
Secondary outcomes:
measure: Efficacy- Graft failure
timeFrame: Day 365
measure: Efficacy- Durability of insulin independence- long term
timeFrame: 2 and 3 years after discontinuation of AT- 1501
measure: Efficacy- HbA1c
timeFrame: Day 365 and free of serious hypoglycemic events from Day 28 to 365 post-first transplant
Other outcomes:
measure: Exploratory- Hypoglycemia unawareness (using the method of Clarke)
timeFrame: Day 75, 365, and 1, 2 and 3 years after discontinuation of AT-1501
measure: Exploratory- Glycemic lability (using CGMS)
timeFrame: Day 75, 365, and 1, 2 and 3 years after discontinuation of AT-1501
measure: Exploratory- Glycemic variability (using CGMS)
timeFrame: Day 75, 365, and 1, 2 and 3 years after discontinuation of AT-1501
measure: Exploratory- Albumin excretion ratio (AER)
timeFrame: Day 365 post-first, and final transplant
measure: Exploratory- eGRF
timeFrame: Day 365 post-first, and final transplant
measure: Exploratory- Macroalbuminemia
timeFrame: Day 365 post-first, and final transplant
measure: Exploratory- biomarkers of tissue damage and inflammation
timeFrame: Day -2, 3, 14, 28, 75, 175, 364
measure: Exploratory -Pharmacokinetic Parameters-AUC
timeFrame: T=0 (pre infusion), 1 (end of infusion), 2, 4, 8, 12, 24 and 48 hrs.
measure: Exploratory- Pharmacokinetic Parameters-Cmax
timeFrame: T=0 (pre infusion), 1 (end of infusion), 2, 4, 8, 12, 24 and 48 hrs.
measure: Exploratory- Pharmacokinetic Parameters-CL
timeFrame: T=0 (pre infusion), 1 (end of infusion), 2, 4, 8, 12, 24 and 48 hrs.
measure: Exploratory- Pharmacokinetic Parameters- Vdss
timeFrame: T=0 (pre infusion), 1 (end of infusion), 2, 4, 8, 12, 24 and 48 hrs.
measure: Exploratory- Pharmacokinetic Parameters- (t1/2)
timeFrame: T=0 (pre infusion), 1 (end of infusion), 2, 4, 8, 12, 24 and 48 hrs.
Locations:
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
Study officials:
affiliation: Eledon Pharmaceuticals
name: Jeff Bornstein, MD
role: STUDY_CHAIR
References: