PolyTreg Immunotherapy for Type 1 Diabetes

Overseen By Parastoo Dinyari, BSc

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Alberta

Must be taking: Tacrolimus, Sirolimus

Must not be taking: Steroids, Anticoagulants

Disqualifiers: Cardiac disease, Substance abuse, others

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new immunotherapy approach for individuals with difficult-to-control Type 1 diabetes. The treatment uses a type of immune cell called PolyTregs, which may reduce the need for multiple islet transplants and lower the side effects of current treatments. Participants will receive either the standard islet transplant or the transplant plus the new PolyTregs treatment. The trial seeks individuals with Type 1 diabetes who have struggled with low blood sugar awareness or unstable blood sugar levels despite intensive insulin efforts. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications, but all participants will be maintained on low dose tacrolimus and sirolimus, which are medications that suppress the immune system. It's best to discuss your current medications with the trial team to understand any potential changes.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that Treg cell therapy, such as PolyTregs, has been safe in past studies. Safety checks found no major health differences between patients who received Treg therapy and those who did not. These studies primarily examined any unwanted effects or unusual lab results. The findings indicated that the treatment did not cause serious health problems. Additionally, this therapy has been used in people with type 1 diabetes for up to 12 years with good results, suggesting long-term safety. Although this trial is just starting, these earlier findings are encouraging for the safety of PolyTregs. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for Type 1 Diabetes focus on managing blood sugar levels and include insulin therapy. However, PolyTregs offers a unique approach by using regulatory T cells (Tregs) to potentially modulate the immune system. Unlike standard treatments, PolyTregs aims to address the root cause of Type 1 Diabetes by preventing the immune system from attacking insulin-producing cells in the pancreas. Researchers are excited about this treatment because it could lead to a more long-term solution, reducing the need for frequent insulin administration and offering better preservation of the body's ability to produce insulin naturally.

What evidence suggests that PolyTregs might be an effective treatment for Type 1 Diabetes?

Research has shown that certain cells, called Regulatory T cells (Tregs), help control the immune system and prevent it from attacking the body's own cells. In people with Type 1 diabetes, these Tregs often malfunction. Studies suggest that increasing the number of these cells might protect the insulin-producing cells in the pancreas, which are usually under attack in Type 1 diabetes. Early evidence indicates that using these Tregs can help the pancreas function better for a longer time. In this trial, participants in the experimental arm will receive a PolyTregs infusion, potentially reducing the need for insulin in people with Type 1 diabetes. Meanwhile, the control arm will receive an islet transplant only, without PolyTregs. ^{3 6 7 8 9}

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 adults aged 18-68 with Type 1 Diabetes (T1DM) for over 5 years, who have hypoglycemia unawareness or unstable blood sugar despite trying hard to manage it. They must understand the study and agree to participate. People can't join if they have certain untreated diseases, severe kidney issues, heavy insulin requirements, a history of substance abuse, are pregnant/breastfeeding or planning pregnancy.

Inclusion Criteria

I have had Type 1 Diabetes for over 5 years.

I understand the study's risks and have signed the consent form.

You have trouble noticing when your blood sugar gets too low or have unstable metabolism even with careful insulin management.

Exclusion Criteria

You have or have had a condition where too much protein is found in your urine.

I am pregnant, planning to become pregnant, not using birth control, or breastfeeding.

Your HbA1C level is higher than 12%.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Islet Transplant

Participants undergo islet transplant according to standard procedures with lower doses of Tacrolimus/Sirolimus for immunosuppression

1 day

1 visit (in-person)

PolyTreg Infusion

Participants in the treatment group receive PolyTregs infusion 6 weeks post-islet transplant and are monitored for 24 hours

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with regular blood tests and assessments

58 weeks

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• PolyTregs

Trial Overview The trial tests PolyTregs therapy in patients receiving an islet transplant for T1DM. It's an open-label pilot study comparing standard Edmonton induction therapy alone versus with additional PolyTregs infusion post-transplant. The goal is to see if PolyTRegs make the transplant more successful by improving beta cell function and reducing immune system rejection.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

Participants in this arm receive PolyTregs infusion at week 6 post islet transplant.

Group II: Control Active Control 1 Intervention

Participants in this arm receive islet transplant only, and no PolyTregs.

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Alberta Diabetes Institute

Collaborator

Trials

5

Recruited

130+

Juvenile Diabetes Research Foundation

Collaborator

Trials

237

Recruited

142,000+

Diabetes Research Institute Foundation

Collaborator

Trials

10

Recruited

80+

Liana's Dream Foundation

Collaborator

Trials

1

Recruited

10+

Citations

1. oaepublish.com oaepublish.com/articles/mtod.2024.52

Regulatory T cell-based therapies for type 1 diabetes Adoptive transfer of autologous polyclonal Tregs has proven safe and partly effective in restoring immune tolerance and preserving beta cell function among T1D ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4729454/

Type 1 diabetes immunotherapy using polyclonal regulatory T ... Regulatory T cells (Tregs) have been shown to be defective in the autoimmune disease setting. Thus, efforts to repair or replace Tregs in T1D may reverse ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02772679

T1DM Immunotherapy Using Polyclonal Tregs + IL-2 The purpose of this study is to assess the safety of Tregs + IL-2 and survival of Tregs in patients with recent onset T1DM who receive infusions of autologous ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0896841119301659

Regulatory T cells engineered with a novel insulin-specific ... Our data demonstrate that our converted, insulin-specific CAR Tregs (cTregs) were functional stable, suppressive and long-lived in vivo.

5. science.org science.org/doi/10.1126/scitranslmed.adn2404

A phase 2 randomized trial with autologous polyclonal ... In autoimmune type 1 diabetes (T1D), adoptive transfer of autologous polyclonal Tregs has been shown to be safe in adults in phase 1 clinical ...

6. poltreg.com poltreg.com/positive-results-of-a-long-term-safety-and-efficacy-study-of-ptg-007-in-early-onset-type-1-diabetes/

Positive results of a long-term safety and efficacy study ... – Safety measures showed no significant difference in the health status of patients who received Treg therapy compared to the control group, – ...

7. poltreg.com poltreg.com/poltreg-treg-cell-therapy-for-patients-with-type-1-diabetes-shows-long-term-clinical-remission-and-insulin-independence/

PolTREG Treg cell therapy for patients with type-1 diabetes ... Treatment with its Treg cell therapy, PTG-007, resulted in clinical remission for up to 12 years in patients with type-1 diabetes (T1D).

8. biospace.com biospace.com/poltreg-s-type-1-diabetes-treg-cell-therapy-ptg-007-demonstrates-long-term-safety-and-efficacy-for-up-to-12-years

PolTREG's type-1 diabetes Treg cell therapy PTG-007 ... PolTREG SA announces that its polyclonal Treg cell therapy PTG-007 demonstrated significant insulin secretion restoration in early-onset type-1 diabetes ...

9. firstwordpharma.com firstwordpharma.com/story/5985585

PolTREG and U.S. Subsidiary Immuthera Secure Positive ... FDA agreed that PolTREG's clinical data in Stage 3 Type 1 Diabetes (T1D) appears sufficient to support the Prospect of Direct benefit in an ...