cePolyTregs in Islet Transplantation

NCT05349591 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: Pro00117578
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The transplant of the insulin-producing cell into the liver (Islet transplant) has been proven an effective and valuable treatment for type 1 diabetics patients with poor blood sugar. However, Islet transplant is currently limited by the number of pancreas organ donors and the need for lifelong medication requirements such as antirejection drugs. The investigators have learned that Regulatory T cells (Tregs), a small subset of a cluster of differentiation 4+ (CD4+) T cells, have emerged as the major contributor to self-tolerance by preventing the initiation of unwanted immune activation and by suppressing ongoing immune responses to limit bystander tissue destruction. It has been suggested that infusion of Tregs before extensive graft damage may improve long-term graft outcomes. In this trial, we propose to study Analogous cryopreserved PolyTregs (cePolyTregs). cePolyTregs is a product with the same in vivo functionality to that of the non-cryopreserved PolyTregs.

Conditions

Diabetes type1

Keywords

Islet Transplantation; cePolytregs; Cryopreserved; Immunotherapy; Diabetes treatment; Immunosuppression

Outcome Measures

Primary Outcomes (1)

• Adverse Events

  Any adverse event presented during the study

  58 weeks

Secondary Outcomes (4)

• Stimulated C-peptide level

  Baseline

• Stimulated C-peptide level

  Day 30 post Islet transplantation

• Stimulated C-peptide level

  Day 90 post Islet transplantation

• Stimulated C-peptide level

  Week 58 post Islet transplantation

Study Arms (2)

Control

NO INTERVENTION

The Participants in this arm receive islet transplant only and no cePolyTregs.

Treatment

EXPERIMENTAL

Participants will receive cePolyTregs (target 400-1600 million, with a minimal acceptable dose of 100 million) two weeks post islet transplant and will be followed for 1 year after cePolyTregs infusion to assess the safety and preliminary efficacy of cePolyTregs therapy.

Biological: cePolytreg

Interventions

cePolytreg BIOLOGICAL

The treatment group will receive cePolyTregs 2 weeks after islet transplantation as immunotherapy to improve islet survival and reduce the need for immunosuppression drugs.

Treatment

Eligibility Criteria

• Age: 18 Years - 68 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible, subjects must be 18-68 years old, and have had T1DM for more than 5 years, complicated by at least 1 of the following situations that persist despite intensive insulin management efforts:
• Reduced awareness of hypoglycemia, as defined by the absence of adequate autonomic symptoms at plasma glucose levels \< 3.0 mmol/L, indicated by, 1 or more episodes of severe hypoglycemia requiring third party assistance within 12 months, or a Clarke score ≥4, or HYPO score ≥1000, or lability index (LI) ≥400 or combined HYPO/LI \>400/\>300.
• Metabolic instability, characterized by erratic blood glucose levels that interfere with daily activities and or 1 or more hospital visits for diabetic ketoacidosis over the last 12 months.
• In addition, participants must be capable of understanding the purpose and risks of the study and must sign a statement of informed consent.

You may not qualify if:

• Patients will be excluded if they meet any one or more of the following criteria:
• Severe co-existing cardiac disease, characterized by any one of these conditions: (a) recent myocardial infarction (within past 6 months); (b) left ventricular ejection fraction \<30%; or (c) evidence of ischemia on functional cardiac exam
• Active alcohol or substance abuse (must be abstinent for 6 months prior to transplant)
• Clinical history of T1DM diagnosed \>age 40, insulin dependent \<5 years
• Active infection including Hepatitis C, Hepatitis B, HIV, TB (subjects with a positive PPD performed within one year of enrolment, and no history of adequate chemoprophylaxis)
• Measured glomerular filtration rate (GFR) \< 60mL/min/1.73 m2
• Presence or history of macroalbuminuria (\>300 mg/g creatinine)
• Clinical suspicion of nephritic (hematuria, active urinary sediment) or rapidly progressing renal impairment (e.g. Increase in serum creatinine of 25% within the last 3-6 months)
• Baseline Hb \< 105g/L (\<10.5 g/dL) in women, or \< 120 g/L (\<12 g/dL) in men
• Untreated proliferative retinopathy
• Positive pregnancy test, intent for future pregnancy, failure to follow effective contraceptive measures, or presently breast feeding
• Previous transplant or evidence of significant sensitization on PRA (at the discretion of the investigator).
• Insulin requirement \>1.0 U/kg/day
• HbA1C \>12%
• Uncontrolled hyperlipidemia \[fasting LDL cholesterol \> 3.4 mmol/L (133 mg/dL), treated or untreated; and/or fasting triglycerides \> 2.3 mmol/L (90 mg/dL)\]

Sponsors & Collaborators

• University of Alberta: lead
• Juvenile Diabetes Research Foundation: collaborator
• Juvenile Diabetes Research Foundation Canadian Clinical Trial Network: collaborator

Study Sites (1)

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Study Officials

• James Shapiro, MD/PhD

  University of Alberta

  PRINCIPAL INVESTIGATOR

• Indri Purwana, PhD

  University of Alberta

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2022
• First Posted: April 27, 2022
• Study Start: August 15, 2022
• Primary Completion: May 22, 2025
• Study Completion: May 22, 2025
• Last Updated: June 17, 2025

Record last verified: 2025-06

Locations

CA (1)