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
Overview
- Phase
- Phase 1
- Intervention
- BMF-219
- Conditions
- Type 2 Diabetes Mellitus
- Sponsor
- Biomea Fusion Inc.
- Enrollment
- 443
- Locations
- 35
- Primary Endpoint
- Safety Assessments
- Status
- Completed
- Last Updated
- 5 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy Subject Inclusion Criteria:
- •Males or females, age ≥18 and ≤65 years.
- •BMI ≥18 and ≤35 kg/m
- •Subjects are healthy on the basis of their medical history, physical examination, ECG, and routine laboratory data.
- •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:
- •Males or females, age ≥18 and ≤65 years.
- •Diagnosed with T2D within the last 15 years.
- •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.
- •HbA1c ≥7.0% and ≤10.5%.
Exclusion Criteria
- •Healthy Subject Exclusion Criteria:
- •Evidence or history of any clinically significant disease or malignancy.
- •Mean QTcF ≥ 440 msec on triplicate ECGs. Use of medications known to significantly prolong the QT or QTcF interval.
- •History of hypertension or untreated hypertension (sitting systolic blood pressure (BP) ≥140 and diastolic BP ≥90 mm Hg).
- •Known self or family history (first-degree relative) of multiple endocrine neoplasia Type
- •History of stomach or intestinal surgery or resection (except appendectomy, hernia repair, and/or cholecystectomy).
- •A history or evidence of HIV, HCV, or HBV infection at screening or active COVID-19 infection on screening.
- •Receiving an investigational intervention or having participated in another clinical trial within 30 days.
- •Currently dieting (formal weight loss program) and/or are currently using or have used within 2 months of screening any drugs for weight management.
- •Received prior menin inhibitor treatment.
Arms & Interventions
Phase 1 SAD Cohorts
Phase 1 SAD Cohorts with healthy adults randomized 3:1 receiving BMF-219 or placebo. A pair of sentinel subjects (randomly assigned 1 active drug and 1 placebo) will be dosed 48 hours prior to dosing of the remainder of subjects in each cohort.
Intervention: BMF-219
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.
Intervention: BMF-219
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).
Intervention: BMF-219
Phase 2 MAD Cohorts
Phase 2 MAD Cohorts with healthy adults (MAD 1, randomized 3:1) or adults with T2D (MAD 2-4 \& 6-8, randomized 5:1) receiving BMF-219 or placebo. MAD 5 is BMF-219 only.
Intervention: BMF-219
Phase 2 Expansion Cohort
Phase 2 Expansion Cohort adults with T2D randomized 3:1 ratio receiving BMF-219 or placebo.
Intervention: BMF-219
Outcomes
Primary Outcomes
Safety Assessments
Time Frame: 52 weeks
Assessed by treatment emergent adverse events. (TEAEs), drug discontinuation due to TEAEs, serious adverse events, clinically significant laboratory, vital, and ECG evaluations.
Pharmacokinetics Assessments
Time Frame: 12 weeks
Assessed by effect of fed conditions on serial and sparse pharmacokinetic data.
Change in HbA1c
Time Frame: 26 weeks
Assess the change in HbA1c from baseline to week 26.
Secondary Outcomes
- To assess the effect on HbA1c(26 Weeks)