Clinical trial NCT05731544: Study of BMF-219 in Healthy Adult Subjects and in Adult Subjects With Type 2 Diabetes Mellitus (T2D)
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Type 2 Diabetes Mellitus
Keywords: Diabetes
Type 2 Diabetes Mellitus
Healthy Volunteers
Lead sponsor: Biomea Fusion Inc.
Sponsor class: INDUSTRY
First posted: 2023-02-16
Enrollment: 414
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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), Expansion Cohort will explore 100mg and 200mg dose levels.

Eligibility criteria: 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.

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.
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.
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 HIV, HCV, or HBV infection at screening or active COVID-19 infection on screening.
7. Receiving an investigational intervention or having participated in another clinical trial within 30 days.
8. Currently dieting (formal weight loss program) and/or are currently using or have used within 2 months of screening any drugs for weight management.
9. 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, fasting C-peptide \<0.8 ng/mL, fasting insulin \>55 μIU/mL.
6. Mean QTcF ≥450 ms. Use of medications known to significantly prolong the QT or QTc interval.
7. Fasting triglyceride ≥500 mg/dL.
8. Have an eGFR \<60 mL/min/1.73 Equation at screening.
9. AST or 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.
10. History of acute or chronic pancreatitis and serum lipase and/or amylase above 1.5 x ULN.
11. Active HBV or active HCV at screening. Known positive test, if any, prior to screening or history of HIV. An active COVID-19 infection at screening.
12. TSH \>6 mIU/L or \<0.4 mIU/L (on stable thyroid replacement dose for 3 months prior to screening).
13. Severe uncontrolled treated or untreated hypertension (systolic blood pressure \>150 mmHg or diastolic blood pressure \>90 mmHg).
14. History of stomach or intestinal surgery or resection and/or gastroparesis (except that appendectomy, hernia repair, and/or cholecystectomy will be allowed).
15. History of cirrhosis.
16. Currently dieting (formal weight loss program) and/or are currently using or have used within 2 months of screening any drugs for weight management.

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, fasting C-peptide \<0.8 ng/mL, fasting insulin \>55 μIU/mL.
7. 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.
8. Fasting triglyceride ≥500 mg/dL.
9. eGFR\<60 mL/min/1.73.
10. AST or ALT \>1.5 × ULN, Total bilirubin \>1.5 × ULN at screening.
11. History of acute or chronic pancreatitis and serum lipase and/or amylase above 1.5 x ULN.
12. Active HBV or active HCV at screening. Known positive test or history of HIV. An active COVID-19 infection at screening.
13. TSH \>6 mIU/L or \<0.4 mIU/L (on stable thyroid replacement dose for 3 months prior to screening).
14. Severe uncontrolled treated or untreated hypertension (systolic blood pressure \>150 mmHg or diastolic blood pressure \>90 mmHg).
15. History of stomach or intestinal surgery or resection and/or gastroparesis.
16. History of cirrhosis.
17. Currently dieting (formal weight loss program) and/or are currently using or have used within 2 months of screening any drugs for weight management.

Primary outcomes:
measure: Safety Assessments
timeFrame: 52 weeks
measure: Pharmacokinetics Assessments
timeFrame: 12 weeks
measure: Change in HbA1c
timeFrame: 26 weeks
Secondary outcomes:
measure: To assess the effect on HbA1c
timeFrame: 26 Weeks
Other outcomes:
measure: Exploratory: To determine the effects of BMF-219 on glycemic parameters in subjects with T2D.
timeFrame: Week 26
measure: Exploratory: To determine the impact of multiple ascending doses of BMF-219 on beta-cell function in subjects with T2D.
timeFrame: Week 26
Locations:
city: Canoga Park
country: United States
facility: Hope Clinical Research
state: California
city: Fountain Valley
country: United States
facility: Ark Clinical Research, LLC
state: California
city: Huntington Park
country: United States
facility: Velocity Clinical Research
state: California
city: La Mesa
country: United States
facility: Velocity Clinical Research
state: California
city: Long Beach
country: United States
facility: Ark Clinical Research
state: California
city: Montclair
country: United States
facility: Catalina Research Institute, LLC
state: California
city: San Bernardino
country: United States
facility: Metro Clinical Trials
state: California
city: Hamden
country: United States
facility: CMR of Greater New Haven, LLC
state: Connecticut
city: Fort Myers
country: United States
facility: Southwest General Healthcare Center
state: Florida
city: Hialeah
country: United States
facility: G+C Research Group
state: Florida
city: Homestead
country: United States
facility: Sunbright Health Research Centers
state: Florida
city: Hudson
country: United States
facility: Diabetes Care Center
state: Florida
city: Miami Lakes
country: United States
facility: Panax Clinical Research
state: Florida
city: Miami
country: United States
facility: Avantis Clinical Research
state: Florida
city: Miami
country: United States
facility: Century Research LLC
state: Florida
city: Miami
country: United States
facility: Entrust Clinical Research
state: Florida
city: Orlando
country: United States
facility: Omega Research Orlando
state: Florida
city: Cordele
country: United States
facility: David Kavtaradze MD, Inc
state: Georgia
city: Savannah
country: United States
facility: Privia Medical Group
state: Georgia
city: Chicago
country: United States
facility: Cedar Crosse Research Center
state: Illinois
city: Saint Louis
country: United States
facility: IMA Clinical Research St. Louis
state: Missouri
city: Las Vegas
country: United States
facility: Santa Rosa Medical Centers of Nevada
state: Nevada
city: Brooklyn
country: United States
facility: Omera Health
state: New York
city: New York
country: United States
facility: IMA Clinical Research Manhattan
state: New York
city: Shelby
country: United States
facility: Carolina Research Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Health Network, LLC, Medical Plaza
state: North Carolina
city: Canton
country: United States
facility: Diabetes and Endocrinology Associates of Stark County
state: Ohio
city: Elizabethton
country: United States
facility: Medical Care, LLC
state: Tennessee
city: Austin
country: United States
facility: IMA Clinical Research
state: Texas
city: Dallas
country: United States
facility: Velocity Clinical Research
state: Texas
city: Dallas
country: United States
facility: Zenos Clinical Research
state: Texas
city: Houston
country: United States
facility: Synergy Groups Medical LLC
state: Texas
city: Houston
country: United States
facility: Synergy Group Medical
state: Texas
city: Missouri City
country: United States
facility: Synergy Group Medical
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, LLC
state: Texas
city: San Antonio
country: United States
facility: Diabetes & Glandular Disease Clinic, P.A.
state: Texas
city: Sugar Land
country: United States
facility: Simcare Medical Research
state: Texas
city: Waco
country: United States
facility: Velocity Clinical Research
state: Texas
city: Jordan
country: United States
facility: Velocity Clinical Research
state: Utah
city: Manassas
country: United States
facility: Manassas Clinical Research
state: Virginia
city: Vancouver
country: Canada
facility: BC Diabetes
state: British Columbia
city: Brampton
country: Canada
facility: Centricity Research Brampton Endocrinology
state: Ontario
city: Toronto
country: Canada
facility: Centricity Research LMC
state: Ontario
city: Toronto
country: Canada
facility: BioPharma Services Inc.
Study officials:
References: