临床试验/NCT05731544

NCT05731544已完成1 期

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

Biomea Fusion Inc.35 个研究点分布在 2 个国家目标入组 443 人开始时间: 2022年8月17日最近更新: 2025年11月10日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Biomea Fusion Inc.
入组人数: 443
试验地点: 35
主要终点: Safety Assessments

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验相关资讯

研究概览

简要总结

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.

详细描述

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.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
主要目的: Treatment
盲法: Double (Participant, Investigator)

盲法说明

The subject and the investigator involved in the treatment or clinical evaluation of the subjects will be unaware of the group assignments.

入排标准

年龄范围: 18 Years 至 65 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 是

入选标准

•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%.
•BMI ≥25 and ≤40 kg/m
•Females are to be not pregnant, non-lactating.
•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:
•Males or females, age ≥18 and ≤65 years.
•Diagnosed with T2D within the last 7 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%.
•BMI ≥25 and ≤40 kg/m
•Females are to be not pregnant, non-lactating.
•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.

排除标准

•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.
•Subjects with T2D (MAD Cohorts) Exclusion Criteria:
•Type 1 Diabetes Mellitus or a secondary form of diabetes or any prior history of diabetic ketoacidosis.
•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.
•Known self or family history (first-degree relative) of multiple endocrine neoplasia Type
•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.
•Fasting plasma glucose ≥255 mg/dL, fasting C-peptide <0.8 ng/mL, fasting insulin >55 μIU/mL.
•Mean QTcF ≥450 ms. Use of medications known to significantly prolong the QT or QTc interval.
•Fasting triglyceride ≥500 mg/dL.
•Have an eGFR <60 mL/min/1.73 Equation at screening.
•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.
•History of acute or chronic pancreatitis and serum lipase and/or amylase above 1.5 x ULN.
•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.
•TSH >6 mIU/L or <0.4 mIU/L (on stable thyroid replacement dose for 3 months prior to screening).
•Severe uncontrolled treated or untreated hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg).
•History of stomach or intestinal surgery or resection and/or gastroparesis (except that appendectomy, hernia repair, and/or cholecystectomy will be allowed).
•History of cirrhosis.
•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:
•Type 1 Diabetes Mellitus or a secondary form of diabetes.
•Prior history of diabetic ketoacidosis or hyperosmolar coma.
•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.
•Known self or family history (first-degree relative) of multiple endocrine neoplasia Type 1 (MEN1).
•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.
•Fasting plasma glucose ≥255 mg/dL, fasting C-peptide <0.8 ng/mL, fasting insulin >55 μIU/mL.
•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.
•Fasting triglyceride ≥500 mg/dL.
•eGFR<60 mL/min/1.
•AST or ALT >1.5 × ULN, Total bilirubin >1.5 × ULN at screening.
•History of acute or chronic pancreatitis and serum lipase and/or amylase above 1.5 x ULN.
•Active HBV or active HCV at screening. Known positive test or history of HIV. An active COVID-19 infection at screening.
•TSH >6 mIU/L or <0.4 mIU/L (on stable thyroid replacement dose for 3 months prior to screening).
•Severe uncontrolled treated or untreated hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg).
•History of stomach or intestinal surgery or resection and/or gastroparesis.
•History of cirrhosis.
•Currently dieting (formal weight loss program) and/or are currently using or have used within 2 months of screening any drugs for weight management.

研究组 & 干预措施

Phase 1 SAD Cohorts

Experimental

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.

干预措施: BMF-219 (Drug)

Phase 1 single dose food effect sub-study

Experimental

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.

干预措施: BMF-219 (Drug)

Phase 1 single dose tablet PK sub-study

Experimental

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).

干预措施: BMF-219 (Drug)

Phase 2 MAD Cohorts

Experimental

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.

干预措施: BMF-219 (Drug)

Phase 2 Expansion Cohort

Experimental

Phase 2 Expansion Cohort adults with T2D randomized 3:1 ratio receiving BMF-219 or placebo.

干预措施: BMF-219 (Drug)

结局指标

主要结局

Safety Assessments

时间窗: 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

时间窗: 12 weeks

Assessed by effect of fed conditions on serial and sparse pharmacokinetic data.

Change in HbA1c

时间窗: 26 weeks

Assess the change in HbA1c from baseline to week 26.

次要结局

To assess the effect on HbA1c(26 Weeks)

研究者

发起方

Biomea Fusion Inc.

申办方类型

Industry

责任方

Sponsor

研究点 (35)

Loading locations...

相似试验

已完成

1 期

Safety and Tolerability of Intravenous LLP2A-Alendronate for Osteopenia Secondary to GlucocorticoidsOsteopeniaOsteonecrosisOsteoporosis

NCT03197623Nancy E. Lane, MD58

已完成

1 期

Study Evaluating Safety, Tolerability, and Efficacy of Intravenous AP-SA02 in Subjects With S. Aureus BacteremiaStaphylococcus AureusStaphylococcus Aureus BacteremiaBacteremia StaphBacteremia Due to Staphylococcus AureusBacteremia

NCT05184764Armata Pharmaceuticals, Inc.56

已完成

1 期

A Phase 1 Single and Multiple-Dose Study of Aramchol in Healthy Male VolunteersHealthy

NCT00776841Galmed Medical Reserch41

进行中（未招募）

1 期

Multiple Ascending Dose Study of CG200745 'Ivaltinostat' Oral CapsuleHematologic MalignancySolid TumorFibrosis

NCT05716919Machaon Biotherapeutics, Inc.32

已完成

1 期

Phase 1 Study for IPG11406 in Health VolunteerInflammatory Bowel Diseases

NCT06255834Nanjing Immunophage Biotech Co., Ltd66