Phase 2 Trial of BMF-219 in Participants With Type 1 Diabetes Mellitus (BF-MNN-112)

Phase 2 Randomized, Double-blind Trial of BMF-219 Compared to Placebo in Participants With Type 1 Diabetes Mellitus

Phase 2 Trial of BMF-219 in Participants with Type 1 Diabetes Mellitus.

Study Overview

• Status: Terminated
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: BMF-219

Detailed Description

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 participants with T1D treated with BMF-219. BMF-219 is an orally bioavailable, covalent small-molecule menin inhibitor.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Dr. T.G Elliott Inc. dba BC Diabetes
  • Ontario
    • Toronto, Ontario, Canada
      • Centricity Research
• United States
  • Florida
    • North Miami Beach, Florida, United States, 33169
      • Oceanic Research Group
  • North Carolina
    • Morehead City, North Carolina, United States, 28577
      • Lucas Research, Inc.
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Alliance for Multispecialty Research, LLC.
  • Tennessee
    • Chattanooga, Tennessee, United States, 37411
      • University Diabetes & Endocrine Consultants
  • Texas
    • Dallas, Texas, United States, 75230
      • Velocity Clinical Research
    • Round Rock, Texas, United States, 78681
      • Texas Diabetes & Endocrinology
    • San Antonio, Texas, United States, 78229
      • Diabetes & Glandular Disease Clinic, P.A.
    • Shavano Park, Texas, United States, 78231
      • Consano Clinical Research, LLC
  • Virginia
    • Manassas, Virginia, United States, 20110
      • Manassas Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males or females, age ≥18 and ≤70 years.

2. Diagnosed with stage 3 T1D within the following timeframes:

   • Part 1 Cohort 1: Participants diagnosed within 3 years prior to screening.
   • Part 1 Cohort 2: Participants diagnosed between 3 to 15 years prior to screening
   • Part 2 : Participants diagnosed within 15 years prior to screening.

3. Treated with insulin only for at least 2 months prior to screening and proficient in the following in the opinion of the investigator:

   • Counting carbohydrates
   • Adjusting meal and correction boluses based on glucose readings with a stable insulin/carbohydrate ratio as well as correction factors
   • Adjusting insulin and dietary therapy during special situations (eg, exercise, stress, intermittent diseases)
4. HbA1c ≥6.5 and ≤10.0% at screening.

5. Fasting or stimulated C-peptide Concentration at Screening as follows:

   • C-peptide concentration ≥0.2 nmol/L if diagnosed within 3 years prior to screening.
   • C-peptide concentration ≥0.08 nmol/L if diagnosed between 3 and 15 years prior to screening.
6. Documented history of at least 1 T1D1-related autoantibody.
7. If treated with lipid-lowering therapy, the dose must be stable for at least 30 days prior to screening.
8. Men and women of childbearing potential must use adequate birth control measures for the duration of the trial and at least 90 days after discontinuing study treatment.
9. Women who are not pregnant or lactating.

Exclusion Criteria:

1. Diagnosis of MODY, T2D or any other subtype of diabetes mellitus other than T1D.
2. Have had recurrence (≥2 episodes) of severe hypoglycemia
3. Known self or family history (first-degree relative) of multiple endocrine neoplasia Type 1.
4. Use of diabetes medications except insulin within 2 months prior to screening.
5. Any significant cardiovascular disease or QTcF prolongation within the last 6 months prior to screening.
6. Participants with fasting triglyceride ≥500 mg/dL.
7. Have an eGFR <60 mL/min/1.73 m2 by the CKDEPI Creatinine Equation at screening.
8. Impaired liver function, defined as screening AST or ALT >1.5 × ULN, Total bilirubin >1.5 × ULN with the exception of Gilbert's Syndrome.
9. History of acute or chronic pancreatitis, complete pancreatectomy or pancreas transplants.
10. Serum lipase and/or amylase above 1.5 x ULN.
11. Known positive test for HIV, HBV surface antigen and COVID-19.
12. Diagnosis of, or treatment for, any cancer within the last 2 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ, melanoma in situ) treated with potentially curative therapy.
13. Active (symptomatic) celiac disease.
14. History of stomach or intestinal surgery that would potentially alter absorption and/or excretion of orally administered drugs.
15. History of cirrhosis.
16. Currently participating in a formal weight loss program and/or are currently using any drugs for weight management within 2 months of screening.
17. Use of Proton pump inhibitors (PPIs) is prohibited.
18. Treatment with a moderate or strong CYP3A4 inhibitor, inducer, or substrate within a week prior to dosing on Day 1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1; 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	Drug: BMF-219; BMF-219 is an orally bioavailable, covalent small-molecule menin inhibitor.
Experimental: Part 2; 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	Drug: BMF-219; BMF-219 is an orally bioavailable, covalent small-molecule menin inhibitor.
Placebo Comparator: Placebo Comparator; Part 2 Study Double Blind Arm C matching placebo for 12 weeks.	Drug: BMF-219; BMF-219 is an orally bioavailable, covalent small-molecule menin inhibitor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the effect on endogenous insulin secretion	Mean change from baseline in stimulated C-peptide AUC.	26 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the effect on endogenous insulin secretion	Maximum stimulated C-peptide: the highest value at any time point during the 4-hour MMTT.	26 Weeks
To assess the effect on additional glycemic parameters	Mean change from baseline in HbA1c.	26 Weeks of treatment
To assess the effect on additional glycemic parameters	Mean change from baseline in FPG.	26 Weeks
To assess hypoglycemia events	Percentage of participants with hypoglycemic episodes (with confirmed self-plasma glucose monitoring) including level 2 hypoglycemic events (<54 mg/dL regardless of symptoms) and level 3 (severe) hypoglycemia across different timepoints.	26 weeks
To assess the effect on insulin doses	Change from baseline in mean daily insulin dosing.	26 Weeks
Rate of symptomatic hypoglycemic episodes	Evaluation and comparison of the number of symptomatic (both minor and severe) hypoglycemic episodes with BMF-219 vs placebo during the study.	26 Weeks and during study duration
Incidence of adverse events	Evaluation and comparison of the number of adverse events with BMF-219 vs placebo during the study.	26 Weeks and during study duration

Collaborators and Investigators

• Sponsor: Biomea Fusion Inc.
• Investigators: Study Director: Juan Pablo Frias, MD, Biomea Fusion Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2023
• Primary Completion (Actual): May 20, 2025
• Study Completion (Actual): July 18, 2025

Study Registration Dates

• First Submitted: November 10, 2023
• First Submitted That Met QC Criteria: November 21, 2023
• First Posted (Actual): November 30, 2023

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 1
• Other Study ID Numbers: COVALENT-112

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No