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

Phase 2
Withdrawn
Conditions
Type 1 Diabetes Mellitus
Interventions
Registration Number
NCT04711226
Lead Sponsor
Anelixis Therapeutics, LLC
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.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
AT-1501 Single ArmAT-1501-
Primary Outcome Measures
NameTimeMethod
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 independenceDays 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 Outcome Measures
NameTimeMethod
Efficacy- Graft failureDay 365

Proportion of participants with graft failure

Efficacy- Durability of insulin independence- long term2 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- HbA1cDay 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

Trial Locations

Locations (1)

University of Alberta

🇨🇦

Edmonton, Alberta, Canada

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