BMF-219 for Type 1 Diabetes

(BF-MNN-112 Trial)

No longer recruiting at 33 trial locations

Overseen By Sanchita Mourya

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Biomea Fusion Inc.

Must be taking: Insulin

Must not be taking: PPIs, CYP3A4 drugs

Disqualifiers: MODY, T2D, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, BMF-219 (a covalent menin inhibitor), for individuals with Type 1 Diabetes. The goal is to determine if BMF-219 can manage blood sugar levels more effectively than current treatments. Participants will receive either a low dose, high dose, or a placebo (a non-active pill) for 12 weeks. This trial suits those who have managed Type 1 Diabetes with insulin for over two months and are accustomed to adjusting their insulin based on daily activities like exercise. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

The trial requires that you have only been treated with insulin for at least 2 months before screening and prohibits the use of other diabetes medications during that time. Additionally, you cannot use proton pump inhibitors or certain other medications that affect liver enzymes within a week before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that BMF-219 is being explored as a potential treatment for Type 1 Diabetes. This treatment aims to regenerate beta cells to help the body produce more insulin, which could aid in managing the disease. Safety data from other studies, such as the COVALENT-111 study, indicate that BMF-219 has been tested in people with Type 2 Diabetes. In those studies, most participants tolerated the treatment well, experiencing no serious side effects.

Another study examined the safety of BMF-219 in healthy adults, finding the treatment manageable with no major safety issues reported. Since the trial for Type 1 Diabetes is in an advanced stage, some evidence already supports the treatment's safety in humans. This suggests that while side effects can occur, they are not expected to be severe for most people. ^{1 2 3 4 5}

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

BMF-219 is unique because it targets type 1 diabetes in a novel way. Unlike standard treatments like insulin therapy, which manage blood sugar levels, BMF-219 works by modulating a specific protein involved in the disease process. Researchers are excited about BMF-219 because it has the potential to address the underlying causes of type 1 diabetes rather than just its symptoms. This could mean a significant advancement in how we treat and understand this condition.

What evidence suggests that this trial's treatments could be effective for Type 1 Diabetes?

Research shows that BMF-219 is a new treatment that blocks a protein called menin, which helps the pancreas grow more beta cells to produce insulin. Insulin is crucial for controlling blood sugar levels in people with Type 1 Diabetes. Early studies suggest that this treatment can improve blood sugar control and enhance beta cell function. In this trial, participants will receive either BMF-219 at varying doses or a placebo in different arms. Participants in previous studies showed significant improvements after using BMF-219 for a short time. These promising results offer hope for those seeking new ways to manage Type 1 Diabetes effectively. ^{2 3 6 7 8}

Who Is on the Research Team?

Juan Pablo Frias, MD

Principal Investigator

Biomea Fusion Inc.

Are You a Good Fit for This Trial?

Adults aged 18-60 with Type 1 Diabetes diagnosed within the last 3 years are eligible for this trial. They must be using only insulin to manage their diabetes, have an HbA1c level between 6.5% and 10%, a BMI of up to 40 kg/m2, and certain levels of C-peptide.

Inclusion Criteria

Your C-peptide concentration is equal to or greater than 0.2 nmol/L (0.60 μg/L).

If your C-peptide level is between 0.15 to 0.20 nmol/L when fasting, but goes above 0.20 nmol/L after a test, you may still be eligible.

If you were diagnosed within the last 3 years and your C-peptide level is equal to or greater than 0.2 nmol/L (0.60 μg/L), you can participate. If your fasting C-peptide level is between 0.15 to 0.20 nmol/L (0.45 to 0.60 μg/L), a stimulated C-peptide level greater than 0.20 nmol/L (0.60 μg/L) is also acceptable.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BMF-219 or placebo for 12 weeks in a randomized, double-blind, placebo-controlled design

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of insulin secretion and hypoglycemic events

26 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• BMF-219

Trial Overview The trial is testing BMF-219 in people with Type 1 Diabetes to see how effective it is. Participants will receive BMF-219 under controlled conditions to monitor its impact on their blood sugar control and overall health.

How Is the Trial Designed?

Group I: Part 2 Experimental Treatment 1 Intervention

Part 2 Part 2 uses a randomized, double-blind, placebo-controlled design with parallel assignment among 3 treatment arms. Eligible participants will be randomly assigned to 1 of 3 arms using a 1:1:1 ratio: * Arm A: BMF-219 100 mg QD for 12 weeks * Arm B: BMF-219 200 mg QD for 12 weeks

Group II: Part 1 Experimental Treatment 1 Intervention

Part 1 uses a randomized, open-label design with parallel assignment between 2 treatment arms in each cohort. The Part 1 Eligible participants will be randomly assigned by cohort to 1 of 2 treatment arms: * Cohort 1: Participants with T1D diagnosed within 3 years with C-peptide concentration ≥0.2 nmol/L * Arm A: BMF-219 100 mg QD for 12 weeks * Arm B: BMF-219 200 mg QD for 12 weeks * Cohort 2: Participants with T1D diagnosed between 3 to 15 years with C-peptide concentration ≥0.08 nmol/L. * Arm A: BMF-219 100 mg QD for 12 weeks * Arm B: BMF-219 200 mg QD for 12 weeks

Group III: Placebo Comparator Placebo Group 1 Intervention

Part 2 Study Double Blind Arm C matching placebo for 12 weeks.

Who Is Running the Clinical Trial?

Biomea Fusion Inc.

Lead Sponsor

Trials

5

Recruited

780+

Published Research Related to This Trial

Sotagliflozin significantly improves glycemic control in adults with type 1 diabetes, reducing HbA1c levels and insulin requirements while also enhancing time in the target glucose range, based on a meta-analysis of six trials involving 3,238 participants over 4 to 52 weeks.

While sotagliflozin reduces the incidence of hypoglycemia, it does increase the risk of diabetic ketoacidosis and other side effects, indicating that careful patient management and insulin dose adjustments are necessary to mitigate these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of dual SGLT 1/2 inhibitor sotagliflozin in type 1 diabetes: meta-analysis of randomised controlled trials. Musso, G., Gambino, R., Cassader, M., et al.[2022]

In a phase 3 trial with 1402 patients, those taking sotagliflozin alongside insulin therapy had a significantly higher rate of achieving a glycated hemoglobin level below 7.0% compared to the placebo group (28.6% vs. 15.2%).

While sotagliflozin improved glycemic control and reduced weight and insulin dosage, it was associated with a higher rate of diabetic ketoacidosis (3.0% vs. 0.6% in the placebo group), indicating a need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Sotagliflozin Added to Insulin in Patients with Type 1 Diabetes. Garg, SK., Henry, RR., Banks, P., et al.[2022]

In a 29-week study involving 296 patients with type 1 diabetes, pramlintide combined with reduced mealtime insulin effectively decreased postprandial glucose levels and weight, while both pramlintide and placebo groups showed similar reductions in HbA1c levels.

Although nausea was more common in the pramlintide group, it was mostly mild to moderate, and the rates of severe hypoglycemia were low in both groups, indicating that pramlintide can be a safe adjunct therapy for managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, placebo-controlled trial assessing pramlintide treatment in the setting of intensive insulin therapy in type 1 diabetes. Edelman, S., Garg, S., Frias, J., et al.[2022]

Only 20% of patients with type 1 diabetes achieve adequate control despite advancements in insulin delivery and monitoring, highlighting a significant need for innovative treatments.

Pramlintide is currently the only approved adjunct therapy for type 1 diabetes, while dapagliflozin and sotagliflozin have shown efficacy in reducing HbA1c without increasing hypoglycemia risk, although they are not yet licensed in the U.S. due to concerns about diabetic ketoacidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunct therapies in treatment of type 1 diabetes. Goyal, I., Sattar, A., Johnson, M., et al.[2021]

Citations

1. investors.biomeafusion.com investors.biomeafusion.com/news-releases/news-release-details/biomea-fusion-highlights-initial-data-first-two-type-1-diabetes

Biomea Fusion Highlights Initial Data from the First Two Type ... BMF-219 is an investigational novel covalent menin inhibitor developed to regenerate insulin-producing beta cells with the aim to cure ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06152042

Study Details | NCT06152042 | Phase 2 Trial of BMF-219 ... Study COVALENT-112 is a 52-week, Phase 2 trial designed to examine beta-cell function, insulin sensitivity, and both glucose and lipid metabolism in ...

3. diabetesjournals.org diabetesjournals.org/diabetes/article/73/Supplement_1/901-P/156533/901-P-COVALENT-112-A-Clinical-Trial-Assessing-BMF

901-P: COVALENT 112—A Clinical Trial Assessing BMF-219 ... Background and Aims: Inhibition of menin, a scaffold protein, results in beta cell proliferation and enhanced insulin secretion in T1D.

4. metabolismjournal.com metabolismjournal.com/article/S0026-0495(25)00090-3/fulltext

Investigating the Effects of Icovamenib on Poorly Managed ... Both cases demonstrated significant, sustained improvements in glycemic control and markers of beta-cell function following short-term icovamenib treatment.

5. thejdca.org thejdca.org/publications/report-library/archived-reports/2024-reports/biomea-receives-green-light-for-t1d-practical-cure-trial.html

Biomea Receives Green Light for T1D Practical Cure Trial COVALENT-112 is a phase II trial testing two oral dose levels of BMF-219, a potent and selective covalent menin inhibitor created using the ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05731544

NCT05731544 | Study of BMF-219 in Healthy Adult ... This is a Phase 1/ 2 study that will examine the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple dose levels of BMF ...

7. diabetesjournals.org diabetesjournals.org/diabetes/article/74/Supplement_1/272-OR/159649/272-OR-COVALENT-111-26-Week-Efficacy-and-Safety

272-OR: COVALENT-111: 26-Week Efficacy and Safety after 8 ... In the MAD phase of the COVALENT-111 trial, 4 wks of daily icovamenib in patients with T2D significantly improved A1C at 26 wks. This was most ...

8. firstwordpharma.com firstwordpharma.com/story/5913556

Late-Breaker Oral Presentation Showing New Analysis ... 83% of patients with insulin deficiency responded to icovamenib, and showed a greater mean HbA1c reduction at Week 26 compared to baseline, than ...