CELZ-201 for Type 1 Diabetes

(CREATE-1 Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Camillo Ricordi, MD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Creative Medical Technology Holdings Inc

Must be taking: Insulin

Must not be taking: Immunosuppressants, Immunomodulators

Disqualifiers: Cardiac disease, Liver disease, Hypertension, others

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial is testing CELZ-201, a new treatment for people who have just been diagnosed with Type 1 Diabetes. The treatment is given directly into the bloodstream to help control blood sugar levels.

Will I have to stop taking my current medications?

The trial requires that participants do not use diabetes medications other than insulin and avoid non-insulin drugs that affect blood sugar control within 7 days of screening. If you are on such medications, you may need to stop them before joining the trial.

What data supports the effectiveness of the CELZ-201 treatment for Type 1 Diabetes?

Research on similar treatments, like teplizumab and otelixizumab, shows they can help preserve insulin-producing cells in people with new-onset Type 1 Diabetes. These treatments work by targeting the immune system to protect the cells that make insulin. ^{1 2 3 4 5}

How is the CELZ-201 treatment different from other treatments for type 1 diabetes?

CELZ-201 (AlloStem) is unique because it potentially involves a novel approach to treating type 1 diabetes by targeting the autoimmune response that destroys insulin-producing cells, unlike traditional treatments that primarily focus on insulin replacement. ^{6 7 8 9 10}

Research Team

Camillo Ricordi, MD

Principal Investigator

University of Miami, Diabetes Research Institute

Eligibility Criteria

Adults aged 18-35 with recent onset Type 1 Diabetes, confirmed by specific autoantibodies and a certain level of C-peptide. Participants must be mentally stable, able to follow the study protocol, manage their diabetes as usual, have good kidney function and venous access for blood draws. Women must not be pregnant or breastfeeding and along with men, agree to use two forms of birth control during the study.

Inclusion Criteria

Subjects must be willing to comply with 'standard-of-care' diabetes management

Subject must be able to understand and provide signed informed consent

I am mentally stable and can follow study instructions.

Exclusion Criteria

You have an eating disorder.

Your HbA1c level is higher than 9%.

My blood pressure is not higher than 140/90 mmHg.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of CELZ-201 in addition to standard care for Type 1 Diabetes

1 month

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• CELZ-201 Administration (Stem Cell Therapy)

Trial Overview The trial is testing CELZ-201's safety and effectiveness when given through an artery in patients who've recently been diagnosed with Type 1 Diabetes Mellitus. A control group will not receive CELZ-201. The goal is to see if this treatment can help manage diabetes better than current standard care.

Participant Groups

Group I: CELZ-201 Treatment Group Experimental Treatment 1 Intervention

Participants in this group will receive a single dose of CELZ-201, in addition to standard of care of care for Type 1 Diabetes treatment.

Group II: Control Group Placebo Group 1 Intervention

Participants in this group will receive standard of care for Type 1 Diabetes only.

Who Is Running the Clinical Trial?

Creative Medical Technology Holdings Inc

Lead Sponsor

Trials

2

Recruited

50+

Findings from Research

Current treatments for type 1 diabetes focus on insulin replacement, but new therapies aim to preserve insulin-secreting beta cells by targeting the auto reactive T cells that destroy them.

Promising drugs like DiaPep277, Anti-CD3 Otelixizumab, and GAD are being tested in phase 3 clinical trials, showing potential to protect beta cells and improve outcomes for patients with type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical update on the use of immuno modulators (antiCD3, GAD, Diapep277, anti-IL1) in type 1 diabetes. Pozzilli, P., Guglielmi, C., Maggi, D., et al.[2019]

In a 2-year phase 3 study involving 516 patients with new-onset type 1 diabetes, teplizumab significantly reduced the loss of C-peptide levels compared to placebo, indicating its efficacy in preserving insulin production.

The treatment was well-tolerated, with no new safety concerns identified, and certain patient characteristics, such as younger age and lower insulin use at diagnosis, were associated with better responses to teplizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teplizumab preserves C-peptide in recent-onset type 1 diabetes: two-year results from the randomized, placebo-controlled Protégé trial. Hagopian, W., Ferry, RJ., Sherry, N., et al.[2022]

Type 1 diabetes is increasingly common, affecting about 1 in 300 people, and early intervention during the prediabetic phase, identified by islet autoantibodies, is crucial for potential prevention.

Current therapies, including monoclonal antibodies and immunosuppressants, have not yet achieved long-term remission or prevention of type 1 diabetes, highlighting the need for a balance between safety and efficacy in developing new treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention strategies for type 1 diabetes mellitus: current status and future directions. Winter, WE., Schatz, D.[2018]

Recent advancements in antigen-specific immunotherapies for Type 1 diabetes (T1D) aim to restore tolerance to insulin-producing β-cells, but current trials have shown disappointing results, highlighting the need for optimization in treatment protocols.

The review discusses various immunotherapy strategies, including peptides, proteins, and gene transfer, while emphasizing the importance of timing, administration routes, and biomarkers for monitoring treatment efficacy in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A century later, still fighting back: antigen-specific immunotherapies for type 1 diabetes. Rodriguez-Fernandez, S., Almenara-Fuentes, L., Perna-Barrull, D., et al.[2021]

In the Phase III DEFEND-2 trial involving 179 patients (including 54 adolescents), otelixizumab did not significantly preserve C-peptide secretion in patients with new-onset Type 1 diabetes, showing a change from baseline that was not statistically significant (P=0.051).

The study found that the efficacy and tolerability of otelixizumab at a 3.1 mg dose were similar to previous results from DEFEND-1, indicating that this dose was ineffective for both adults and adolescents, and further research is needed to explore higher doses and their mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of low-dose otelixizumab anti-CD3 monoclonal antibody in preserving C-peptide secretion in adolescent type 1 diabetes: DEFEND-2, a randomized, placebo-controlled, double-blind, multi-centre study. Ambery, P., Donner, TW., Biswas, N., et al.[2018]

Type 1 diabetes affects about 370,000 adults in the UK and is characterized by the autoimmune destruction of insulin-producing beta cells, leading to a lack of insulin secretion without insulin resistance.

NICE guidelines recommend structured education for newly diagnosed patients within 12 months and suggest an optimal insulin regimen of twice daily long-acting insulin (detemir) combined with rapid-acting insulin at mealtimes to ensure effective self-management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving the detection and management of type 1 diabetes. Hammond, P.[2016]

Soluble antigen arrays (SAgAs) effectively prevent the onset of type 1 diabetes (T1D) in a mouse model, showing superior efficacy compared to individual peptide treatments, particularly when using stable click chemistry linkers (cSAgAs).

SAgAs not only enhance the engagement of antigen-specific T cells and promote tolerance markers but also significantly reduce the risk of anaphylaxis associated with free peptide treatments, making them a safer option for antigen-specific immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Soluble Antigen Arrays Efficiently Deliver Peptides and Arrest Spontaneous Autoimmune Diabetes. Firdessa-Fite, R., Johnson, SN., Leon, MA., et al.[2023]

Antigen-based immunotherapy, which selectively targets autoreactive T cells involved in Type 1 diabetes, shows promise in preventing or treating the disease, as demonstrated in animal models like the NOD mouse.

Peptide immunotherapies derived from autoantigens such as GAD65 and insulin have been effective in delaying the onset of diabetes, but challenges remain in translating these findings to human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide immunotherapies in Type 1 diabetes: lessons from animal models. Fierabracci, A.[2019]

Type 1A diabetes is caused by the autoimmune destruction of insulin-producing beta cells, with insulin identified as a primary autoantigen that plays a crucial role in the disease's development.

Research indicates that immunization with specific insulin peptides can either induce or prevent diabetes in animal models, suggesting that targeting insulin autoantibodies could be a potential therapeutic strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin as a primary autoantigen for type 1A diabetes. Jasinski, JM., Eisenbarth, GS.[2022]

The novel multi-epitope vaccine developed for type 1 diabetes successfully induced specific antibodies and improved glucose metabolism in non-obese diabetic (NOD) mice, leading to better blood glucose control and increased insulin levels.

Immunization with this vaccine not only reduced the incidence of diabetes and insulitis but also promoted a favorable immune response by increasing IL-10 and decreasing IFN-γ, suggesting its potential as a therapeutic approach for managing type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Construction of a novel vaccine by conjugating a B-cell epitope of DPP4 to peptide IA2(5)-P2-1 to significantly control type 1 diabetes in NOD mice. Li, Y., Cao, H., Li, Y., et al.[2018]

References

1. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Clinical update on the use of immuno modulators (antiCD3, GAD, Diapep277, anti-IL1) in type 1 diabetes. [2019]

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

Teplizumab preserves C-peptide in recent-onset type 1 diabetes: two-year results from the randomized, placebo-controlled Protégé trial. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Prevention strategies for type 1 diabetes mellitus: current status and future directions. [2018]

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

A century later, still fighting back: antigen-specific immunotherapies for type 1 diabetes. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of low-dose otelixizumab anti-CD3 monoclonal antibody in preserving C-peptide secretion in adolescent type 1 diabetes: DEFEND-2, a randomized, placebo-controlled, double-blind, multi-centre study. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Improving the detection and management of type 1 diabetes. [2016]

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

Soluble Antigen Arrays Efficiently Deliver Peptides and Arrest Spontaneous Autoimmune Diabetes. [2023]

8. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Peptide immunotherapies in Type 1 diabetes: lessons from animal models. [2019]

9. Egypt pubmed.ncbi.nlm.nih.gov

Insulin as a primary autoantigen for type 1A diabetes. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Construction of a novel vaccine by conjugating a B-cell epitope of DPP4 to peptide IA2(5)-P2-1 to significantly control type 1 diabetes in NOD mice. [2018]