Islet Transplantation Using PKX-001

NCT03073577 | Completed Phase 1 DMC

• 1 other identifier: Pro00067564
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Islet Transplantation is a procedure used in people with difficult to control Type 1 Diabetes. Insulin producing cells (islets) are isolated from a deceased donor pancreas. After the cells are carefully isolated from the donor pancreas, the islets are transplanted into the recipient's liver. These transplanted islets may produce insulin. One of the challenges with islet transplant is the death of some of the transplanted islets due to inflammation, oxidative stress and exposure to diabetogenic immunosuppressive agents associated with islet functional impairment and graft loss, especially linked to the use of calcineurin inhibitors, including tacrolimus (Tac). Antiaging glycopeptide (PKX-001) is a small, stable, synthetic replica of antifreeze proteins (AFPs), which naturally occur in Arctic and Antarctic fish and have been shown protecting cells against harmful conditions. PKX-001 is a new drug that has been shown in lab studies to help islet cells survive isolation and keep them healthy and functioning. Most importantly, animal studies have shown that islets treated with PKX-001 were protected from the immunosuppressant (Tac) toxicity and retained their function in animals receiving islet transplant. This study will involve up to 10 participants from the islet transplant waiting list at the Clinical Islet Transplant Program. All participants will receive islets treated with the medication PKX-001. PKX-001 will be used only in the islet preservation process, and will not be given to participants as medication. The purpose of this study is to confirm the safety of transplantation of PKX-001 treated islets and to evaluate the cytoprotective capacity of PKX-001 in islet transplantation, especially its capacity to protect against Tac induced graft dysfunction.

Conditions

Type 1 Diabetes Mellitus

Keywords

Type 1 Diabetes Mellitus; Islet Transplantation; Diabetes; Diabetes Treatment

Outcome Measures

Primary Outcomes (2)

• Adverse event morbidity

  Adverse event morbidity within 1 year post-transplant

  Up to 1 year post-transplant

• Serious adverse event morbidity

  Adverse event morbidity within 1 year post-transplant

  Up to 1 year post-transplant

Secondary Outcomes (8)

• Number of participants with insulin independence

  Day 90 post-transplant

• Islet yield

  Day 0

• Engraftment index

  Day 90 post-transplant

• Islet viability

  Day 0

• Glucose stimulated insulin release

  Day 0

Study Arms (1)

Treatment Group

EXPERIMENTAL

PKX-001 will be supplemented to islet preservation CMRL-1066 medium at final concentration of 3 mg/mL during islet isolation process. On the day of transplantation, preserved islets supplemented with PKX-001 are collected and washed with Transplant Media, which does not contain PKX-001, as a standard procedure. The isolation team will evaluate the final islet product based on standard assays. Islets are maintained for minimal 6 hours up to 72 hours in supplemented CMRL1066-based media containing PKX-001 until the time of transplant. When product release minimal criteria are met, islets will be clinically transplanted into patients intraportally.

Drug: Antiaging Glycopeptide

Interventions

Antiaging Glycopeptide DRUG

Antiaging Glycopeptide (PKX-001) will be supplemented to islet preservation medium during islet isolation process. On the day of transplantation, preserved islets supplemented with PKX-001 are collected and washed with Transplant Media, which does not contain PKX-001, as a standard procedure. The isolation team will evaluate the final islet product based on standard assays used in standard of care practice. When product release minimal criteria are met, islets will be clinically transplanted into patients intraportally by percutaneous transhepatic access.

Also known as: PKX-001, AAGP

Treatment Group

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 the participant must have had type 1 diabetes mellitus (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, a Clarke score ≥4, hypoglycemic (HYPO) score ≥1,000, 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.
• Participants must be capable of understanding the purpose and risks of the study and must sign a statement of informed consent.
• All control participants will be included according to the immunosuppression / engraftment regimen used in this pilot, specifically the current standard of care islet transplant at the University of Alberta Hospital: Alemtuzumab/Basiliximab, Anakinra, Etanercept, Mycophenolate Mofetil and Tacrolimus.

You may not qualify if:

• History of enrollment in any other islet transplant trials (at the discretion of the investigator).
• Severe co-existing cardiac disease, characterized by any one of these conditions: (a) recent (within the past 6months) myocardial infarction; (b) left ventricular ejection fraction \<30%; or (c) evidence of ischemia on functional cardiac exam.
• Active alcohol or substance abuse, to include cigarette smoking (must be abstinent for 6 months prior to listing for transplant).
• Psychiatric disorder making the patient not a suitable candidate for transplantation (e.g., schizophrenia, bipolar disorder, or major depression that is unstable or uncontrolled on current medication).
• History of non-adherence to prescribed regimens.
• Active infection including Hepatitis C, Hepatitis B, HIV, or Tuberculosis (TB) (subjects with a positive purified protein derivative (PPD) performed within one year of enrollment, and no history of adequate chemoprophylaxis).
• Any history of, or current malignancies except squamous or basal skin cancer.
• BMI \> 35 kg/m2 at screening visit.
• Age less than 18 or greater than 68 years.
• Measured glomerular filtration rate (GFR) \<60 mL/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.
• Baseline screening liver function tests outside of normal range, with the exception of uncomplicated Gilbert's Syndrome. An initial liver function test (LFT) panel with any values \>1.5 times the upper limit of normal (ULN) will exclude a patient without a re-test; a re-test for any values between ULN and 1.5 times ULN should be made, and if the values remain elevated above normal limits, the patient will be excluded.
• Untreated proliferative retinopathy.

Sponsors & Collaborators

• University of Alberta: lead
• ProtoKinetix Inc.: collaborator

Study Sites (1)

University of Alberta

Edmonton, Alberta, T6G2C8, Canada

Location

Related Links

• related information

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus

Interventions

AAGP glycopeptide, 580 Da

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• James Shapiro, MD, PhD

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2017
• First Posted: March 8, 2017
• Study Start: February 17, 2017
• Primary Completion: May 7, 2025
• Study Completion: May 7, 2025
• Last Updated: May 13, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)