Phase 2 Trial of BMF-219 in Participants with Type 1 Diabetes Mellitus
- Registration Number
- NCT06152042
- Lead Sponsor
- Biomea Fusion Inc.
- Brief Summary
Phase 2 Trial of BMF-219 in Participants with Type 1 Diabetes Mellitus.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 190
-
Males or females, age ≥18 and ≤70 years.
-
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.
-
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)
-
HbA1c ≥6.5 and ≤10.0% at screening.
-
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.
-
Documented history of at least 1 T1D1-related autoantibody.
-
If treated with lipid-lowering therapy, the dose must be stable for at least 30 days prior to screening.
-
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.
-
Women who are not pregnant or lactating.
- Diagnosis of MODY, T2D or any other subtype of diabetes mellitus other than T1D.
- Have had recurrence (≥2 episodes) of severe hypoglycemia
- Known self or family history (first-degree relative) of multiple endocrine neoplasia Type 1.
- Use of diabetes medications except insulin within 2 months prior to screening.
- Any significant cardiovascular disease or QTcF prolongation within the last 6 months prior to screening.
- Participants with fasting triglyceride ≥500 mg/dL.
- Have an eGFR <60 mL/min/1.73 m2 by the CKDEPI Creatinine Equation at screening.
- Impaired liver function, defined as screening AST or ALT >1.5 × ULN, Total bilirubin >1.5 × ULN with the exception of Gilbert's Syndrome.
- History of acute or chronic pancreatitis, complete pancreatectomy or pancreas transplants.
- Serum lipase and/or amylase above 1.5 x ULN.
- Known positive test for HIV, HBV surface antigen and COVID-19.
- 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.
- Active (symptomatic) celiac disease.
- History of stomach or intestinal surgery that would potentially alter absorption and/or excretion of orally administered drugs.
- History of cirrhosis.
- Currently participating in a formal weight loss program and/or are currently using any drugs for weight management within 2 months of screening.
- Use of Proton pump inhibitors (PPIs) is prohibited.
- Treatment with a moderate or strong CYP3A4 inhibitor, inducer, or substrate within a week prior to dosing on Day 1.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1 BMF-219 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 Part 2 BMF-219 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 Placebo Comparator BMF-219 Part 2 Study Double Blind Arm C matching placebo for 12 weeks.
- Primary Outcome Measures
Name Time Method To assess the effect on endogenous insulin secretion 26 Weeks Mean change from baseline in stimulated C-peptide AUC.
- Secondary Outcome Measures
Name Time Method To assess the effect on endogenous insulin secretion 26 Weeks Maximum stimulated C-peptide: the highest value at any time point during the 4-hour MMTT.
To assess the effect on additional glycemic parameters 26 Weeks Mean change from baseline in FPG.
To assess the effect on insulin doses 26 Weeks Change from baseline in mean daily insulin dosing.
Incidence of adverse events 26 Weeks and during study duration Evaluation and comparison of the number of adverse events with BMF-219 vs placebo during the study.
Rate of symptomatic hypoglycemic episodes 26 Weeks and during study duration Evaluation and comparison of the number of symptomatic (both minor and severe) hypoglycemic episodes with BMF-219 vs placebo during the study.
To assess hypoglycemia events 26 weeks 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.
Trial Locations
- Locations (27)
Sutter Valley Medical Foundation Pediatric Endocrinology
🇺🇸Sacramento, California, United States
Diablo Clinical Research,Inc
🇺🇸Walnut Creek, California, United States
Southwest General Healthcare Center
🇺🇸Fort Myers, Florida, United States
Suncoast Clinical Research, Inc.
🇺🇸New Port Richey, Florida, United States
Oceanic Research Group
🇺🇸North Miami Beach, Florida, United States
Metabolic Research Institute
🇺🇸West Palm Beach, Florida, United States
Atlanta Diabetes Associates
🇺🇸Atlanta, Georgia, United States
Centricity Research
🇨🇦Toronto, Ontario, Canada
Washington University in St. Louis
🇺🇸Saint Louis, Missouri, United States
Palm Research Center
🇺🇸Las Vegas, Nevada, United States
Lucas Research, Inc.
🇺🇸Morehead City, North Carolina, United States
Accellacare of Wilmington
🇺🇸Wilmington, North Carolina, United States
Diabetes and Endocrinology Center
🇺🇸Winston-Salem, North Carolina, United States
Alliance for Multispecialty Research
🇺🇸Norman, Oklahoma, United States
University Diabetes & Endocrine Consultants
🇺🇸Chattanooga, Tennessee, United States
Velocity Clinical Research
🇺🇸Dallas, Texas, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Diabetes and Thyroid Center of Fort Worth
🇺🇸Fort Worth, Texas, United States
PlanIt Research, PLLC
🇺🇸Houston, Texas, United States
Tekton Research
🇺🇸McKinney, Texas, United States
Texas Diabetes & Endocrinology
🇺🇸Round Rock, Texas, 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
Manassas Clinical Research Center
🇺🇸Manassas, Virginia, United States
BC Diabetes
🇨🇦Vancouver, British Columbia, Canada