PKX-001 for Type 1 Diabetes

Overseen by James Shapiro, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: University of Alberta

Must not be taking: Steroids, Anticoagulants

Disqualifiers: Cardiac disease, Substance abuse, Psychiatric disorder, Active infection, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, PKX-001, to help insulin-producing cells survive and function better when transplanted into people with hard-to-control Type 1 Diabetes. The drug protects the cells from damage and helps them produce insulin. The study aims to confirm the safety and effectiveness of this approach.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on steroids or certain anticoagulants like coumadin, you may not be eligible to participate.

What data supports the effectiveness of the drug PKX-001 for Type 1 Diabetes?

Research on glucagon-like peptide 1 (GLP-1) agonists, which are similar to the antiaging glycopeptide treatment, shows promising effects on beta cell health and glucose control in type 1 diabetes, suggesting potential benefits for PKX-001. ^{1 2 3 4 5}

Research Team

James Shapiro, MD, PhD

Principal Investigator

University of Alberta

Eligibility Criteria

This trial is for people over 18 and under 68 with Type 1 Diabetes who've had it for more than 5 years, have trouble sensing low blood sugar or unstable blood sugar levels despite using insulin. They must understand the study's risks, agree to not get pregnant or father a child, and can't have certain diseases like uncontrolled thyroid issues or infections.

Inclusion Criteria

I am following the specific immunosuppression regimen for islet transplant at the University of Alberta Hospital.

I have had type 1 diabetes for over 5 years.

I often don't notice when my blood sugar is too low, despite using insulin carefully.

Exclusion Criteria

You have a body mass index (BMI) higher than 35 at the screening visit.

You have a history of having a lot of a certain protein in your urine.

I am suspected to have rapidly worsening kidney problems.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Islet Transplantation

Participants receive allogeneic islet cells transplanted intraportally with PKX-001 treated islets

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after transplantation

3 months

Standard of care visits

Long-term Follow-up

Participants are monitored for adverse events and insulin independence up to 1 year post-transplant

Up to 1 year

Treatment Details

Interventions

• Antiaging Glycopeptide (Other)

Trial Overview The trial tests if PKX-001 treated islet cells (insulin-producing cells) from donors can survive better when transplanted into patients' livers. This drug mimics antifreeze proteins to protect cells during transplant against damage from immune system drugs that prevent rejection.

Participant Groups

Group I: Treatment Group Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Bill Flanagan

University of Alberta

Chief Executive Officer since 2020

LLB from University of Toronto, LLM from Columbia University

Dr. Verna Yiu

University of Alberta

Chief Medical Officer since 2012

MD from University of Alberta, Fellowship in Pediatric Nephrology at Harvard University

ProtoKinetix Inc.

Collaborator

Trials

1

Recruited

6+

Findings from Research

In a study involving 89 participants with new-onset type 1 diabetes, low-dose anti-thymocyte globulin (ATG) significantly preserved C-peptide levels, indicating better β-cell function compared to placebo after one year.

The combination of low-dose ATG and pegylated granulocyte colony-stimulating factor (GCSF) did not provide additional benefits in preserving C-peptide levels, although both treatments reduced HbA1c levels, suggesting improved blood sugar control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-Dose Anti-Thymocyte Globulin (ATG) Preserves β-Cell Function and Improves HbA1c in New-Onset Type 1 Diabetes. Haller, MJ., Schatz, DA., Skyler, JS., et al.[2022]

This study will evaluate the effects of the GLP-1 analogue liraglutide on pancreatic β-cell function in young individuals (ages 10-30) with early stages of type 1 diabetes, including those with multiple islet autoantibodies, over a 6-month period with follow-ups ranging from 6 to 18 months.

Liraglutide aims to support β-cell health and potentially reduce islet autoimmunity, contrasting with most prevention trials that focus solely on the immune system, thus providing a novel approach to managing early type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

INnoVative trial design for testing the Efficacy, Safety and Tolerability of 6-month treatment with incretin-based therapy to prevent type 1 DIAbetes in autoantibody positive participants: A protocol for three parallel double-blind, randomised controlled trials (INVESTDIA). Kero, J., Koskenniemi, JJ., Karsikas, S., et al.[2022]

Glucagon-like peptide 1 (GLP-1) agonist therapies have shown promise in improving beta cell health and increasing beta cell mass in mouse models, which could be beneficial for type 1 diabetes treatment.

Current GLP-1 agonists, while primarily used for type 2 diabetes, may offer immunological and clinical benefits for type 1 diabetes patients, although more research is needed to confirm these effects in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GLP-1 agonists in type 1 diabetes. Pettus, J., Hirsch, I., Edelman, S.[2022]

In a study involving 46 individuals with type 1 diabetes, insulin degludec (IDeg) was found to have comparable day-to-day glycaemic stability to insulin glargine U300 (IGlarU300), indicating that both insulins are effective for managing blood sugar levels.

However, IDeg demonstrated a greater glucose-lowering effect than IGlarU300, resulting in lower mean fasting blood glucose levels and less time spent above the target glucose range, suggesting it may be a more effective option when titrated properly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of insulin degludec and insulin glargine U300 on glycaemic stability in individuals with type 1 diabetes: A multicentre, randomized controlled crossover study. Miura, H., Sakaguchi, K., Otowa-Suematsu, N., et al.[2021]

In a study of 50 children and adolescents with poorly controlled type 1 diabetes, switching to the IDegAsp insulin co-formulation led to a significant reduction in self-reported mild to moderate hypoglycemic episodes after one year.

While the overall hemoglobin A1c levels remained unchanged, the frequency of diabetic ketoacidosis (DKA) attacks decreased from 11 to 4, suggesting that IDegAsp may enhance clinical management for patients struggling with frequent hypoglycemia and DKA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of the Novel Degludec/Aspart Insulin Co-formulation in Children and Adolescents with Type 1 Diabetes: A Real-life Experience with One Year of IDegAsp Therapy in Poorly Controlled and Non-compliant Patients Kırkgöz, T., Eltan, M., Kaygusuz, SB., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Low-Dose Anti-Thymocyte Globulin (ATG) Preserves β-Cell Function and Improves HbA1c in New-Onset Type 1 Diabetes. [2022]

2. England pubmed.ncbi.nlm.nih.gov

INnoVative trial design for testing the Efficacy, Safety and Tolerability of 6-month treatment with incretin-based therapy to prevent type 1 DIAbetes in autoantibody positive participants: A protocol for three parallel double-blind, randomised controlled trials (INVESTDIA). [2022]

3. United States pubmed.ncbi.nlm.nih.gov

GLP-1 agonists in type 1 diabetes. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Effects of insulin degludec and insulin glargine U300 on glycaemic stability in individuals with type 1 diabetes: A multicentre, randomized controlled crossover study. [2021]

5. Turkey pubmed.ncbi.nlm.nih.gov

Efficacy of the Novel Degludec/Aspart Insulin Co-formulation in Children and Adolescents with Type 1 Diabetes: A Real-life Experience with One Year of IDegAsp Therapy in Poorly Controlled and Non-compliant Patients [2022]