PKX-001 for Type 1 Diabetes

Overseen By Clinical Islet Transplant Program CITP

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Alberta

Must not be taking: Steroids, Anticoagulants

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

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve islet transplantation for individuals with hard-to-control Type 1 Diabetes. It tests a new drug, PKX-001 (also known as Antiaging Glycopeptide), designed to protect insulin-producing cells (islets) from damage during transplantation. The goal is to determine if PKX-001 can maintain the health and function of these cells by shielding them from harmful conditions. Ideal participants have had Type 1 Diabetes for over 5 years, experience severe low blood sugar episodes requiring assistance, or have highly unstable blood sugar that disrupts daily life. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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 prior data suggests that PKX-001 is safe for islet transplantation?

Research has shown that PKX-001, a new drug, helps islet cells stay healthy in lab studies. In animal studies, islets treated with PKX-001 were protected from damage caused by certain transplant drugs. These studies suggest it helps the islets function well after transplantation.

Currently, PKX-001 is in early human trials to assess its safety and tolerability. Researchers are closely monitoring for any side effects. Early results indicate that the primary goal of ensuring safety has been met. However, as human testing is still in its early stages, much remains to be learned about its effectiveness in people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for Type 1 Diabetes, which typically involves insulin therapy and glucose monitoring, PKX-001 introduces an innovative approach by utilizing an antiaging glycopeptide. This treatment is unique because it is integrated into the islet preservation process, potentially enhancing the viability and function of transplanted islets. Researchers are excited about PKX-001 because it targets the preservation and quality of islet cells before transplantation, which could lead to more successful and long-lasting diabetes management compared to current methods.

What evidence suggests that PKX-001 might be an effective treatment for Type 1 Diabetes?

Research has shown that PKX-001, the treatment under study in this trial, may help islet cells survive during transplantation. Lab studies found that this treatment protects cells from harmful conditions. In animal studies, islets treated with PKX-001 continued to function even when exposed to toxic drugs like tacrolimus, commonly used after transplants. This suggests that PKX-001 could help islet cells remain healthy and function better post-transplant. Although more research is needed in humans, these early findings offer promise for improving transplant success in individuals with hard-to-control Type 1 Diabetes. ^{1 2 3 6 7}

Who Is on the Research Team?

James Shapiro, MD, PhD

Principal Investigator

University of Alberta

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Antiaging Glycopeptide

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.

How Is the Trial Designed?

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+

ProtoKinetix Inc.

Collaborator

Trials

1

Recruited

6+

Published Research Related to This Trial

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03073577

NCT03073577 | Islet Transplantation Using PKX-001 Islet Transplantation is a procedure used in people with difficult to control Type 1 Diabetes. Insulin producing cells (islets) are isolated from a deceased ...

2. clinicaltrial.be clinicaltrial.be/en/details/71853?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

Islet Transplantation Using PKX-001 Although islet transplantation outcomes have improved significantly in highly specialized centers with a 5-year insulin independence rate ...

3. protokinetix.com protokinetix.com/applications/transplants/type-1-diabetes/

Type 1 Diabetes We are currently in Phase 1, first-in-human clinical trials to evaluate the safety and tolerability of AAGP® PKX-001 treated Islet cells. PKX-001 is the ...

4. diabetesjournals.org diabetesjournals.org/diabetes/article/65/2/451/40177/Antiaging-Glycopeptide-Protects-Human-Islets

Antiaging Glycopeptide Protects Human Islets Against ... Islet transplantation outcomes have improved significantly in highly specialized centers, with a 5-year insulin independence rate exceeding 50% ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12185959/

Advances in Cell Replacement Therapies for Diabetes - PMC Islet cell replacement therapies have evolved as a viable treatment option for type 1 diabetes complicated by problematic hypoglycemia and glycemic lability.

6. pharmaceutical-business-review.com pharmaceutical-business-review.com/news/protokinetix-achieves-primary-objective-safety-at-midpoint-of-clinical-trial/

ProtoKinetix achieves primary objective safety at midpoint ... The PKX-001 study will treat islet cells prior to transplantation into human test subjects. The clinical trials primary objective is the ...

7. protokinetix.com protokinetix.com/ammendments-to-protokinetix-aagp-protocol-for-continuation-of-phase-1-human-trials-have-been-approved-by-health-canada/

Press Release Islet cell transplants are well recognized as a viable and effective treatment for Type-1 diabetes. The PKX-001 study will treat islet cells ...