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

Type 1 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT06152042
• Other study ID #: COVALENT-112
• Status: Suspended
• Phase: Phase 2
• Start date: December 28, 2023
• Est. completion date: August 31, 2025

Study information

• Verified date: June 2024
• Source: Biomea Fusion Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 190
• Est. completion date: August 31, 2025
• Est. primary completion date: August 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Drug:
• BMF-219
BMF-219 is an orally bioavailable, covalent small-molecule menin inhibitor.

Locations

Country	Name	City	State
Canada	Centricity Research	Brampton	Ontario
Canada	Centricity Research	Ottawa	Ontario
Canada	Centricity Research	Toronto	Ontario
Canada	BC Diabetes	Vancouver	British Columbia
United States	Atlanta Diabetes Associates	Atlanta	Georgia
United States	University Diabetes & Endocrine Consultants	Chattanooga	Tennessee
United States	Centricity Research	Columbus	Georgia
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Velocity Clinical Research	Dallas	Texas
United States	Southwest General Healthcare Center	Fort Myers	Florida
United States	Diabetes and Thyroid Center of Fort Worth	Fort Worth	Texas
United States	PlanIt Research, PLLC	Houston	Texas
United States	Palm Research Center	Las Vegas	Nevada
United States	Manassas Clinical Research Center	Manassas	Virginia
United States	Tekton Research	McKinney	Texas
United States	Lucas Research, Inc.	Morehead City	North Carolina
United States	Suncoast Clinical Research, Inc.	New Port Richey	Florida
United States	Alliance for Multispecialty Research	Norman	Oklahoma
United States	Oceanic Research Group	North Miami Beach	Florida
United States	Texas Diabetes & Endocrinology	Round Rock	Texas
United States	Center of Excellence in Diabetes and Endocrinology	Sacramento	California
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	Clinical Trials of Texas	San Antonio	Texas
United States	Diabetes & Glandular Disease Clinic, P.A.	San Antonio	Texas
United States	Endeavor Clinical Trials, LLC	San Antonio	Texas
United States	Consano Clinical Research, LLC	Shavano Park	Texas
United States	Diablo Clinical Research,Inc	Walnut Creek	California
United States	Metabolic Research Institute	West Palm Beach	Florida
United States	Accellacare of Wilmington	Wilmington	North Carolina
United States	Diabetes and Endocrinology Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Biomea Fusion Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess the effect on endogenous insulin secretion	Mean change from baseline in stimulated C-peptide AUC.	26 Weeks
Secondary	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
Secondary	To assess the effect on additional glycemic parameters	Mean change from baseline in HbA1c.	26 Weeks of treatment
Secondary	To assess the effect on additional glycemic parameters	Mean change from baseline in FPG.	26 Weeks
Secondary	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
Secondary	To assess the effect on insulin doses	Change from baseline in mean daily insulin dosing.	26 Weeks
Secondary	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
Secondary	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