CELZ-201 for Type 1 Diabetes

(CREATE-1 Trial)

Overseen By Creative Medical Technology

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

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 This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 month

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on evaluating the safety and effectiveness of CELZ-201, a new treatment for individuals recently diagnosed with Type 1 Diabetes. It compares this treatment with the usual care patients already receive. Those diagnosed with Type 1 Diabetes within the last year who still produce some insulin (as shown by a lab test) might be suitable for this study. Participants will either receive a single dose of CELZ-201 or continue with their standard diabetes care. As a Phase 1 and Phase 2 trial, the study aims to understand how CELZ-201 works in people and measure its effectiveness in a smaller group, offering participants a chance to be among the first to benefit from this promising treatment.

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.

Is there any evidence suggesting that CELZ-201 is likely to be safe for humans?

Research has shown that CELZ-201 is safe for treating diabetes. In a study involving individuals with Type 2 diabetes, CELZ-201 helped 80% of participants reduce their insulin needs and maintain stable blood sugar levels. Importantly, the study reported no serious side effects, indicating that CELZ-201 is generally well-tolerated, with few or no major safety concerns noted so far. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Type 1 Diabetes, which often involve insulin therapy and lifestyle changes, CELZ-201 introduces a novel approach by potentially targeting the underlying causes of the disease. Researchers are excited because CELZ-201 might work by modulating the immune system to prevent the autoimmune attack on insulin-producing cells in the pancreas. This could lead to a reduction in the dependency on insulin and offer a more long-term solution for managing Type 1 Diabetes. Such an innovative mechanism offers hope for improved quality of life and reduced complications for patients.

What evidence suggests that CELZ-201 might be an effective treatment for Type 1 Diabetes?

Research has shown that CELZ-201, which participants in this trial may receive, may help treat diabetes by reducing the need for insulin and maintaining steady blood sugar levels. In studies with people who have Type 2 Diabetes, CELZ-201 successfully lowered insulin use and maintained stable blood sugar levels, as measured by hemoglobin A1c, 80% of the time. Although this trial targets people with Type 1 Diabetes, the positive results in Type 2 Diabetes are promising. No serious safety issues were reported, suggesting it could be a safe option. While more research is needed for Type 1 Diabetes, these early findings are encouraging. ^{1 3 4 5 6}

Who Is on the Research Team?

Camillo Ricordi, MD

Principal Investigator

University of Miami, Diabetes Research Institute

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• CELZ-201 Administration

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.

How Is the Trial Designed?

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.

CELZ-201 Administration is already approved in United States for the following indications:

Approved in United States as CELZ-201 for:

• Type 1 Diabetes Mellitus (expanded access therapy)

Who Is Running the Clinical Trial?

Creative Medical Technology Holdings Inc

Lead Sponsor

Trials

2

Recruited

50+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05626712

Safety and Efficacy of CELZ-201 in Patients With Recent ... The brief purpose of this research study is to learn about the safety and efficacy of intra-arterial administration of CELZ-201 in patients with newly diagnosed ...

2. biospace.com biospace.com/press-releases/creative-medical-technology-reports-positive-one-year-results-for-allostem-type-2-diabetes-program

Creative Medical Technology Reports Positive One-Year ... Results demonstrate that CELZ-201 achieved an 80% overall efficacy rate in reducing insulin dependency and stabilizing hemoglobin A1c levels, with no serious ...

3. clinicaltrialvanguard.com clinicaltrialvanguard.com/news/allostem-shows-positive-one-year-results-for-type-2-diabetes/

Allostem™ Shows Positive One-Year Results for Type 2 ... The off-the-shelf, allogeneic cell therapy demonstrated an 80% efficacy rate in reducing insulin dependence and stabilizing hemoglobin A1c levels, with no ...

4. hcplive.com hcplive.com/view/celz-201-cuts-insulin-dependency-at-1-year-in-patients-with-type-2-diabetes

CELZ-201 Cuts Insulin Dependency at 1 Year in Patients ... Upon analysis, CELZ-201 achieved an 80% overall efficacy rate in reducing insulin dependency and stabilizing HbA1c levels. Safety analysis ...

5. theglobeandmail.com theglobeandmail.com/investing/markets/markets-news/Tipranks/35743609/creative-medical-technologys-celz-201-a-promising-step-in-diabetes-treatment/

Creative Medical Technology's CELZ-201: A Promising ... ' The study aims to assess the safety and efficacy of CELZ-201, a biological treatment administered intra-arterially, in patients newly ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05626712?cond=NCT05626712&rank=1

Safety and Efficacy of CELZ-201 in Patients With Recent ... The brief purpose of this research study is to learn about the safety and efficacy of intra-arterial administration of CELZ-201 in patients with newly diagnosed ...