Study of BMF-219 in Healthy Adult Subjects and in Adult Subjects With Type 2 Diabetes Mellitus (T2D)

A Phase 1/2 Randomized, Double-Blind, Placebo-Controlled Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, PK, and PD of BMF-219, an Oral Covalent Menin Inhibitor, in Healthy Adults and Adults With T2D

A Phase 1/ 2 Randomized, Double-Blind, Placebo-Controlled Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMF-219, an Oral Covalent Menin Inhibitor, in Healthy Adult Subjects and in Adult Subjects with Type 2 Diabetes Mellitus.

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: BMF-219

Detailed Description

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-219, an orally bioavailable selective covalent inhibitor of menin, in healthy subjects and in subjects with T2D. This study will assess the effect of BMF-219 as single ascending dose (SAD) and multiple ascending dose (MAD).

• Study Type: Interventional
• Enrollment (Estimated): 414
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Sanchita Mourya, MD; Phone Number: 1-844-245-0490; Email: clinicaltrials@biomeafusion.com
• Study Contact Backup: Name: Rima Sakhapara; Phone Number: 1-844-245-0490; Email: clinicaltrials@biomeafusion.com

Study Locations

• Canada
  • Toronto, Canada, M9L 3A2
    • Active, not recruiting
    • BioPharma Services Inc.
  • Alberta
    • Edmonton, Alberta, Canada, T6G2E1
      • Recruiting
      • Alberta Diabetes Institute Clinical Research Unit
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Y 3W2
      • Recruiting
      • BC Diabetes
  • Ontario
    • Brampton, Ontario, Canada, L6S 0C6
      • Recruiting
      • Centricity Research Brampton Endocrinology
    • Toronto, Ontario, Canada, M4G 3E8
      • Recruiting
      • Centricity Research LMC
• United States
  • Arizona
    • Tempe, Arizona, United States, 85282
      • Active, not recruiting
      • Voyage Medical Services
  • California
    • Canoga Park, California, United States, 91303
      • Recruiting
      • Hope Clinical Research
    • Fountain Valley, California, United States, 92708
      • Recruiting
      • Ark Clinical Research, LLC
    • Huntington Park, California, United States, 90255
      • Recruiting
      • Velocity Clinical Research
    • La Mesa, California, United States, 91942
      • Recruiting
      • Velocity Clinical Research
    • Lincoln, California, United States, 95648
      • Recruiting
      • Clinical Trials Research
    • Long Beach, California, United States, 90815
      • Recruiting
      • Ark Clinical Research
    • Montclair, California, United States, 91763
      • Recruiting
      • Catalina Research Institute, LLC
    • San Bernardino, California, United States, 92404
      • Recruiting
      • Metro Clinical Trials
  • Florida
    • Edgewater, Florida, United States, 32132
      • Recruiting
      • Velocity Clinical Research
    • Fort Myers, Florida, United States, 33907
      • Recruiting
      • Southwest General Healthcare Center
    • Hialeah, Florida, United States, 33010
      • Recruiting
      • G+C Research Group
    • Homestead, Florida, United States, 33032
      • Active, not recruiting
      • Sunbright Health Research Centers
    • Hudson, Florida, United States, 24667
      • Recruiting
      • Diabetes Care Center
    • Miami, Florida, United States, 33155
      • Recruiting
      • Avantis Clinical Research
    • Miami, Florida, United States, 33176
      • Recruiting
      • Entrust Clinical Research
    • Miami Lakes, Florida, United States, 33014
      • Recruiting
      • Panax Clinical Research
    • Orlando, Florida, United States, 32808
      • Recruiting
      • Omega Research Orlando
  • Georgia
    • Cordele, Georgia, United States, 31015
      • Recruiting
      • David Kactaradze MD, Inc
    • Johns Creek, Georgia, United States, 30005
      • Active, not recruiting
      • Georgia Clinic
    • Savannah, Georgia, United States, 31406
      • Recruiting
      • Privia Medical Group
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Recruiting
      • Cedar Crosse Research Center
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Recruiting
      • Velocity Clinical Research
  • Michigan
    • Canton, Michigan, United States, 48188
      • Active, not recruiting
      • Voyage Medical Services
  • Missouri
    • Saint Louis, Missouri, United States, 63117
      • Recruiting
      • IMA Clinical Research St. Louis
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Recruiting
      • Santa Rosa Medical Centers of Nevada
  • New York
    • Brooklyn, New York, United States, 11220
      • Recruiting
      • Omera Health
    • New York, New York, United States, 10036
      • Recruiting
      • IMA Clinical Research Manhattan
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Recruiting
      • Tyron Medical Partners
    • Shelby, North Carolina, United States, 28150
      • Recruiting
      • Carolina Research Center
    • Winston-Salem, North Carolina, United States, 27104
      • Recruiting
      • Wake Forest Health Network, LLC, Medical Plaza
  • Ohio
    • Canton, Ohio, United States, 44718
      • Recruiting
      • Diabetes and Endocrinology Associates of Stark County
    • Columbus, Ohio, United States, 43213
      • Recruiting
      • Centricity Research CPU-Ohio
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Recruiting
      • Chattanooga Research & Medicine
    • Elizabethton, Tennessee, United States, 37643
      • Recruiting
      • Medical Care, LLC
  • Texas
    • Austin, Texas, United States, 78745
      • Recruiting
      • IMA Clinical Research
    • Dallas, Texas, United States, 75230
      • Recruiting
      • Zenos Clinical Research
    • Dallas, Texas, United States, 75230
      • Recruiting
      • Velocity Clinical Research
    • Houston, Texas, United States, 77036
      • Recruiting
      • Synergy Groups Medical LLC
    • Houston, Texas, United States, 77061
      • Recruiting
      • Synergy Group Medical
    • Missouri City, Texas, United States, 77459
      • Recruiting
      • Synergy Group Medical
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • Clinical Trials of Texas, LLC
    • Sugar Land, Texas, United States, 77478
      • Recruiting
      • Simcare Medical Research
    • Waco, Texas, United States, 76710
      • Recruiting
      • Velocity Clinical Research
  • Utah
    • Jordan, Utah, United States, 84088
      • Recruiting
      • Velocity Clinical Research
  • Virginia
    • Manassas, Virginia, United States, 20110
      • Recruiting
      • Manassas Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Healthy Subject Inclusion Criteria:

1. Males or females, age ≥18 and ≤65 years.
2. BMI ≥18 and ≤35 kg/m2.
3. Subjects are healthy on the basis of their medical history, physical examination, ECG, and routine laboratory data.
4. Females are to be not pregnant, non-lactating. Females can be postmenopausal. Females of childbearing potential must have a negative pregnancy test at screening and be willing to have additional pregnancy tests during the study.
5. All subjects must be willing and able to provide written, signed informed consent and be willing and able to comply with all study procedures and tests.

Subjects with T2D: (MAD Cohorts) Inclusion Criteria:

1. Males or females, age ≥18 and ≤65 years.
2. Diagnosed with T2D within the last 15 years.
3. Treated with lifestyle management with or without at the most 3 anti-diabetic medications with a stable dose for at least 2 months prior to screening. If on metformin, the stable dose should be at least 500mg/day.
4. HbA1c ≥7.0% and ≤10.5%.
5. BMI ≥25 and ≤40 kg/m2.
6. Females are to be not pregnant, non-lactating. Females can be postmenopausal. Females of childbearing potential must have a negative pregnancy test at screening and be willing to have additional pregnancy tests during the study.
7. All Subjects must be willing and able to provide written, signed informed consent and be willing and able to comply with all study procedures and tests.

Subjects with T2D: (Expansion Cohort) Inclusion Criteria:

1. Males or females, age ≥18 and ≤65 years.
2. Diagnosed with T2D within the last 7 years.
3. Treated with lifestyle management with or without at the most 3 anti-diabetic medications with a stable dose for at least 2 months prior to screening. If on metformin, the stable dose should be at least 500mg/day.
4. HbA1c ≥7.0% and ≤10.5%.
5. BMI ≥25 and ≤40 kg/m2.
6. Females are to be not pregnant, non-lactating. Females can be postmenopausal. Females of childbearing potential must have a negative pregnancy test at screening and be willing to have additional pregnancy tests during the study.
7. All Subjects must be willing and able to provide written, signed informed consent and be willing and able to comply with all study procedures and tests.

Exclusion Criteria:

Healthy Subject Exclusion Criteria:

1. Evidence or history of any clinically significant disease or malignancy.
2. Mean QTcF ≥ 440 msec on triplicate ECGs. Use of medications known to significantly prolong the QT or QTcF interval.
3. History of hypertension or untreated hypertension (sitting systolic blood pressure (BP) ≥140 and diastolic BP ≥90 mm Hg).
4. Known self or family history (first-degree relative) of multiple endocrine neoplasia Type 1.
5. History of stomach or intestinal surgery or resection (except appendectomy, hernia repair, and/or cholecystectomy).
6. A history or evidence of human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) infection at screening or active COVID-19 infection on screening. A COVID-19 infection requiring hospitalization within the past 30 days prior to the screening visit is not allowed.
7. Use of any live vaccines against infectious diseases within 30 days of initiation of investigational product.
8. Current smoker of more than 5 cigarettes per day.
9. Use of proton pump inhibitors is prohibited. Antacids are permitted but must be given a minimum of 2 hrs before or 2 hrs after administration of study drug. Subjects receiving PPIs who switch to H2receptor antagonists are eligible for enrollment in the study.
10. Excessive use (>8 cups/day) of coffee, tea, soda.
11. Receiving an investigational intervention or having participated in another clinical trial within 30 days.
12. Currently dieting (formal weight loss program) and/or are currently using or have used within 2 months of screening any drugs for weight management.
13. Received prior menin inhibitor treatment.

Subjects with T2D (MAD Cohorts) Exclusion Criteria:

1. Type 1 Diabetes Mellitus or a secondary form of diabetes or any prior history of diabetic ketoacidosis.
2. Have had recurrence (≥2 episodes) of severe hypoglycemia (defined by the occurrence of neuroglycopenic symptoms requiring the assistance of another person for recovery) within the last 6 months prior to screening or, has a history of hypoglycemia unawareness or poor recognition of hypoglycemic symptoms as judged by the Investigator.
3. Known self or family history (first-degree relative) of multiple endocrine neoplasia Type 1.
4. Use of anti-diabetes medications (sulfonylureas, insulin, dipeptidyl peptidase-IV inhibitor [DPP-4I] [linagliptin and saxagliptin only] thiazolidinediones) within last 2 months prior to screening.
5. Fasting plasma glucose ≥255 mg/dL.
6. Fasting C-peptide <0.8 ng/ml.
7. Fasting insulin >55 μIU/mL.
8. Mean QTcF ≥450 ms. Use of medications known to significantly prolong the QT or QTc interval.
9. Fasting triglyceride ≥500 mg/dL.
10. Have an eGFR <60 mL/min/1.73 Equation at screening.
11. AST ALT > 1.5 × ULN, bilirubin > 1.5 × ULN. Isolated GGT elevation >2.5 ULN without > 1.5 x ULN AST, ALT and/or total bilirubin but with a history of abnormal LFTs in the last 6 months or a medical history of a liver disorder should be excluded.
12. History of acute or chronic pancreatitis.
13. Serum lipase and/or amylase above 1.5 x ULN.
14. Active hepatitis B virus (HBV) or active hepatitis C virus (HCV) at screening. Known positive test, if any, prior to screening or history of human immunodeficiency virus (HIV). An active COVID-19 infection at screening. A COVID-19 infection requiring hospitalization (or release from the hospital) within the past 30 days prior to the screening visit.
15. Use of any live vaccines against infectious diseases within 30 days of initiation of investigational product.
16. Subjects with positive drug screen (except marijuana [tetrahydrocannabinol (THC)] during screening.
17. TSH >6 mIU/L or <0.4 mIU/L (on stable thyroid replacement dose for 3 months prior to screening).
18. Severe uncontrolled treated or untreated hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg).
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 (e.g., breast carcinoma, cervical cancer in situ, melanoma in situ) treated with potentially curative therapy.
20. History of stomach or intestinal surgery or resection and/or gastroparesis (except that appendectomy, hernia repair, and/or cholecystectomy will be allowed).
21. History of cirrhosis.
22. Current smokers of more than 3 cigarettes per day.
23. Currently dieting (formal weight loss program) and/or are currently using or have used within 2 months of screening any drugs for weight management.
24. Use of Proton pump inhibitors is prohibited. Subjects receiving PPIs who switch to H2-receptor antagonists are eligible for enrollment in the study.
25. History of any illness, underlying medical condition or unstable medical or psychological condition (including drug or alcohol abuse) that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering study drug to the subject.

Subjects with T2D (Expansion Cohort) Exclusion Criteria:

1. Type 1 Diabetes Mellitus or a secondary form of diabetes.
2. Prior history of diabetic ketoacidosis or hyperosmolar coma.
3. History of severe hypoglycemia (defined by the occurrence of neuroglycopenic symptoms requiring the assistance of another person for recovery) within the last 6 months prior to screening or, has a history of hypoglycemia unawareness.
4. Known self or family history (first-degree relative) of multiple endocrine neoplasia Type 1 (MEN1).
5. Use of any of the following anti-diabetes medications within 2 months prior to screening: sulfonylureas, insulin, and the dipeptidyl peptidase-4 inhibitors (DPP4i) linagliptin and saxagliptin (sitagliptin and other DPP4i allowed) thiazolidinones [TZD]) within last 2 months prior to screening.
6. Fasting plasma glucose ≥255 mg/dL.
7. Fasting C-peptide <0.8 ng/ml.
8. Fasting insulin >55 μIU/mL.
9. Mean QTcF interval >450 ms on triplicate ECGs. Use of prescription or over-the-counter medications known to significantly prolong the QT or QTc interval is excluded.
10. Fasting triglyceride ≥500 mg/dL.
11. eGFR<60 mL/min/1.73.
12. (AST) or (ALT) >1.5 × ULN, Total bilirubin >1.5 × ULN at screening.
13. History of acute or chronic pancreatitis.
14. Serum lipase and/or amylase above 1.5 x ULN.
15. Active hepatitis B (HBV) or active hepatitis C virus (HCV) at screening. Known positive test or history of human immunodeficiency virus (HIV). An active COVID-19 infection at screening. A COVID-19 infection requiring hospitalization (or release from the hospital) within the past 30 days prior to the screening visit.
16. Subjects with positive drug screen (except marijuana [tetrahydrocannabinol (THC)]) during screening.
17. TSH >6 mIU/L or <0.4 mIU/L (on stable thyroid replacement dose for 3 months prior to screening).
18. Severe uncontrolled treated or untreated hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg).
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 (e.g., breast carcinoma, cervical cancer in situ, melanoma in situ) treated with potentially curative therapy.
20. History of stomach or intestinal surgery or resection and/or gastroparesis.
21. History of cirrhosis.
22. Current smokers of more than 5 cigarettes per day.
23. Currently dieting (formal weight loss program) and/or are currently using or have used within 2 months of screening any drugs for weight management.
24. Use of Proton pump inhibitors is prohibited. Subjects receiving PPIs who switch to H2-receptor antagonists are eligible for enrollment in the study.
25. Any known or suspected allergy to trial product, similar compounds or excipients. medical or psychological condition (including drug or alcohol abuse) or historical abnormal laboratory values that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering study drug to the subject.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 SAD Cohorts; Phase 1 SAD Cohorts with healthy adults randomized 3:1 receiving BMF-219 or placebo.	Drug: BMF-219; Investigational Product
Experimental: Phase 1 single dose food effect sub-study; Phase 1 single dose food effect sub-study with healthy adults randomized 1:1:1:1:1:1 receiving BMF-219 or placebo fasted, with a low-fat meal, and with a high fat meal.	Drug: BMF-219; Investigational Product
Experimental: Phase 1 single dose tablet PK sub-study; Phase 1 single dose x3 PK tablet open-label sub-study with healthy adults randomized 1:1 receiving BMF-219 or placebo fasted, with a low-fat meal, and with a high-fat meal).	Drug: BMF-219; Investigational Product
Experimental: Phase 2 MAD Cohorts; Phase 2 MAD Cohorts with healthy adults (MAD1) or adults with T2D (MAD 2-8) randomized 3:1 receiving BMF-219 or placebo.	Drug: BMF-219; Investigational Product
Experimental: Phase 2 Expansion Cohort; Phase 2 Expansion Cohort adults with T2D randomized 3:1 ratio receiving BMF-219 or placebo.	Drug: BMF-219; Investigational Product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Assessments	Assessed by treatment emergent adverse events.(TEAEs), drug discontinuation due to TEAEs, serious adverse events, clinically significant laboratory, vital, and ECG evaluations.	52 weeks
Pharmacokinetics Assessments	Assessed by effect of fed conditions on serial and sparse pharmacokinetic data.	12 weeks
Change in HbA1c	Assess the change in HbA1c from baseline to week 12.	12 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the effects of BMF-219 on glycemic parameters in subjects with T2D.	Assess changes in plasma glucose, c-peptide, and insulin at different timepoints both fasted and in response to OGTT.	18 months
To determine the impact of multiple ascending doses of BMF-219 on beta-cell function in subjects with T2D.	Descriptive summaries of homeostatic model assessment beta-cell function %beta and insulin resistance (HOMA-B and HOMA- IR).	18 months
To assess the effect on HbA1c	Proportion of subjects achieving an HbA1c < 7% at Week 12.	12 Months

Collaborators and Investigators

• Sponsor: Biomea Fusion Inc.
• Investigators: Study Director: Stephen Morris, MD, Biomea Fusion Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2022
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: December 26, 2022
• First Submitted That Met QC Criteria: February 7, 2023
• First Posted (Actual): February 16, 2023

Study Record Updates

• Last Update Posted (Actual): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Diabetes; Healthy Volunteers; Type 2 Diabetes Mellitus
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: COVALENT-111

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