MTX228 for Type 1 Diabetes

Overseen By Peter Senior

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Alberta

Must be taking: Insulin

Must not be taking: Corticosteroids, Non-insulin antihyperglycemics

Disqualifiers: Type 2 diabetes, Cardiovascular history, Cancer, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 84

Duration: 12 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the drug MTX228 can help people with Type 1 Diabetes by regrowing insulin-producing cells, potentially reducing the need for insulin shots and improving blood sugar control. Researchers are testing three different doses of MTX228 to determine which is most effective. The trial seeks participants who have had Type 1 Diabetes for at least a year, rely on insulin, and are willing to use a continuous glucose monitor (CGM) to share their data. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use non-insulin antihyperglycemic agents within 30 days before the study. You must continue using insulin as part of the trial.

Is there any evidence suggesting that MTX228 is likely to be safe for humans?

Research shows that MTX228 has not been tested in people with Type 1 Diabetes. However, it has been tried in Type 2 Diabetes, though the optimal dose remains unknown. The study at the University of Alberta aims to determine if MTX228 is safe and effective for people with Type 1 Diabetes.

This is a Phase 2 trial, indicating that the treatment has shown some safety in earlier research, but more information is needed. Phase 2 trials typically seek to find the right dose and monitor for any side effects, so the safety of the medicine remains under careful study. Prospective participants should know that the study will focus on ensuring the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Type 1 Diabetes?

Researchers are excited about MTX228 for Type 1 Diabetes because it offers a novel approach compared to existing treatments like insulin therapy. Unlike standard treatments that primarily focus on managing blood glucose levels, MTX228 targets the underlying autoimmune process of Type 1 Diabetes, potentially altering the disease course itself. This treatment is delivered orally, which could be more convenient than the traditional insulin injections, making it an appealing option for patients seeking easier management of their condition. With multiple dosing options being explored, MTX228 has the potential to provide flexible and effective care tailored to individual needs.

What evidence suggests that MTX228 might be an effective treatment for Type 1 Diabetes?

Research suggests that MTX228 might help regrow insulin-producing cells in people with Type 1 Diabetes. These cells are crucial for managing blood sugar levels, so regrowing them could reduce the need for insulin injections and improve blood sugar control. Although MTX228 has not yet been tested in people with Type 1 Diabetes, its potential to aid cell regrowth is based on its mechanism of action. This trial will evaluate the effectiveness of different doses of MTX228, including 100 mg QD, 100 mg BID, and 200 mg QD. Early research has shown promise for its effectiveness. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for people under 35 with Type 1 Diabetes Mellitus (T1DM) diagnosed within a year and requiring insulin, or those over 35 with T1DM autoantibodies. Participants must have an HbA1c between 6.0 - 10.0%, be willing to wear a CGM device, have had T1DM for at least a year, have good kidney function (eGFR >45), comply with the study protocol, not be overweight (BMI ≤ 35), and have certain levels of C-peptide.

Inclusion Criteria

Able and willing to comply with the study protocol for the duration of the study

Written informed consent must be obtained before any study-related assessment is performed.

I was diagnosed with Type 1 diabetes before 35 and need insulin, or diagnosed after 35 with positive autoantibodies.

Exclusion Criteria

I have a specific type of diabetes caused by a single gene, Type 2, or after pancreas surgery.

I've had more than one severe low blood sugar episode in the last 6 months.

Significant cardiovascular history including myocardial infarction, coronary angioplasty or bypass grafts, valvular disease or repair, unstable angina pectoris, transient ischemic attack, or cerebrovascular accidents within six months prior to entry into the study, congestive heart failure defined as New York Heart Association (NYHA) stage III and IV, uncontrolled hypertension defined as SBP > 160 mmHg and/or DBP > 100 mmHg, symptomatic postural hypotension, use of systemic corticosteroids or other medications influencing insulin sensitivity, use of non-insulin antihyperglycemic agents within prior 30 days, history of significant other major or unstable neurological, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, or urological disorder including previous solid organ or cell transplant, history of cancer other than squamous cell or basal cell carcinoma of the skin not in full remission for at least 5 years before screening, known recreational substance use or psychiatric illness impacting safety or study objectives, history of alcohol or drug abuse or addiction in the previous 12 months, positive pregnancy blood test for women of childbearing age or breast-feeding women, unwillingness to use an effective method of contraception during the study for sexually active male patients or females not surgically sterile, post-menopausal, or using a medically acceptable barrier method of contraception.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive different doses of MTX228 for 3 months to determine the optimal dose for beta-cell regeneration

12 weeks

Regular visits for monitoring and dose adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in C-peptide levels and insulin usage

12 weeks

Visits at Days 84 and 168

Optional Extension

Participants may continue treatment to observe long-term effects on beta-cell regeneration and metabolic responses

Up to 24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MTX228

Trial Overview The study tests different doses of MTX228 in individuals with Type 1 Diabetes to see if it can help regrow insulin-producing beta cells. This could reduce the need for insulin injections and improve blood sugar control. The goal is to find the best dose for further research in a phase IIb study.

How Is the Trial Designed?

Group I: 200 mg QD Active Control 2 Interventions

Participants will be assigned to receive 3 months oral tablet administration of MTX228 at the 200mg BID dose

Group II: 100 mg BID Active Control 2 Interventions

Participants will be assigned to receive 3 months oral tablet administration of MTX228 at the 100mg BID dose

Group III: 100 mg QD Active Control 2 Interventions

Participants will be assigned to receive 3 months oral tablet administration of MTX228 at the 100mg QD dose

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Published Research Related to This Trial

The early stages of type 1 diabetes (T1D) involve harmful interactions between pancreatic beta cells and the immune system, highlighting the need for new therapeutic strategies.

The JDRF-DiabetesUK-INNODIA-nPOD symposium in September 2022 emphasized both promising advancements in understanding T1D and significant gaps that must be filled to improve prevention and treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Islet cells in human type 1 diabetes: from recent advances to novel therapies - a symposium-based roadmap for future research. Cantley, J., Eizirik, DL., Latres, E., et al.[2023]

DPP-4 inhibitors showed some potential in improving the pathogenesis of type 1 diabetes mellitus (T1DM) in preclinical trials, but their clinical efficacy remains uncertain based on current studies.

A meta-analysis of 5 randomized controlled trials indicated that adding DPP-4 inhibitors to insulin therapy resulted in a slight decrease in glycated hemoglobin A1c (HbA1c) levels, but this change was not statistically significant, suggesting that more research is needed to confirm their effectiveness in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DPP-4 Inhibitors as Treatments for Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Wang, Q., Long, M., Qu, H., et al.[2022]

GLP-1 receptor agonists (like exenatide and liraglutide) can significantly lower hemoglobin A1C levels, plasma glucose, and body weight in patients with type 1 diabetes who are already on insulin, without increasing the risk of hypoglycemia.

The most common side effects of GLP-1 RAs are mild and transient gastrointestinal issues, making them a safe option for patients struggling with insulin side effects or those needing to lose weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive Role of Glucagon-Like Peptide-1 Receptor Agonists in the Management of Type 1 Diabetes Mellitus. Harris, KB., Boland, CL.[2022]

Adjunctive agents like sodium glucose cotransporter inhibitors (SGLTis) and glucagon-like peptide (GLP)1 agonists have shown significant reductions in hemoglobin A1c (HbA1c) levels in individuals with type 1 diabetes (T1D), indicating their potential effectiveness in managing blood sugar levels.

There is a need for further studies to explore the cardiovascular risk reduction benefits of these agents in T1D, as current research suggests they may offer advantages beyond just lowering glucose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reducing Type 1 Diabetes Mortality: Role for Adjunctive Therapies? Snaith, JR., Holmes-Walker, DJ., Greenfield, JR.[2021]

Older adults with type 1 diabetes in the T1D Exchange registry showed better management of their condition, with higher usage of antihypertensive medications, statins, and insulin pumps compared to those in the German/Austrian DPV registry, which may contribute to fewer chronic complications.

Despite similar HbA1c levels between the two groups, the T1D Exchange participants had lower rates of myocardial infarctions, strokes, and microvascular complications, indicating that intensive therapy may lead to improved clinical outcomes in older adults with type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Type 1 diabetes in older adults: Comparing treatments and chronic complications in the United States T1D Exchange and the German/Austrian DPV registries. Weinstock, RS., Schütz-Fuhrmann, I., Connor, CG., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06474598

NCT06474598 | An Adaptive Design Study of MTX228 MTX228 has been identified as a medication that might allow the re-growth of insulin producing beta cells in people with Type 1 Diabetes.

2. withpower.com withpower.com/trial/mtx228-for-type-1-diabetes-b101f

MTX228 for Type 1 Diabetes MTX228 has been identified as a medication that might allow the re-growth of insulin producing beta cells in people with Type 1 Diabetes.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12509486/

Autoimmune Type 1 Diabetes in the Era of Disease‐ ... However, clinical approval of the first DMT and multiple clinical trials have demonstrated the efficacy and safety of immune therapies for T1D.

4. centerwatch.com centerwatch.com/clinical-trials/listings/condition/602/diabetes-mellitus-type-1

Diabetes Mellitus Type 1 Clinical Research Trials MTX228 has not been testing in clinical studies in type 1 diabetes and the optimal dose to use is not clear from the clinical trial in type 2 diabetes, where ...

5. clinicaltrials.breakthrought1d.ca clinicaltrials.breakthrought1d.ca/

Breakthrough T1D - Clinical Trials A Research Study to See How a Weekly Insulin, Insulin Icodec, Helps in Reducing the Blood Sugar Compared to Daily Insulin Glargine, Both in Combination With ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06474598/an-adaptive-design-study-of-mtx228

An Adaptive Design Study of MTX228 MTX228 has not been testing in clinical studies in type 1 diabetes and the optimal dose to use is not clear from the clinical trial in type 2 ...

7. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT06474598/

Trial | NCT06474598 MTX228 has not been testing in clinical studies in type 1 diabetes and the optimal dose to use is not clear from the clinical trial in type 2 diabetes, where ...