Clinical trial NCT06152042: Phase 2 Trial of BMF-219 in Participants with Type 1 Diabetes Mellitus
Official title: Phase 2 Randomized, Double-blind Trial of BMF-219 Compared to Placebo in Participants with Type 1 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: Biomea Fusion Inc.
Sponsor class: INDUSTRY
First posted: 2023-11-30
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Males or females, age ≥18 and ≤70 years.
2. 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.
3. 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)
4. HbA1c ≥6.5 and ≤10.0% at screening.
5. 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.
6. Documented history of at least 1 T1D1-related autoantibody.
7. If treated with lipid-lowering therapy, the dose must be stable for at least 30 days prior to screening.
8. 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.
9. Women who are not pregnant or lactating.

Exclusion Criteria:

1. Diagnosis of MODY, T2D or any other subtype of diabetes mellitus other than T1D.
2. Have had recurrence (≥2 episodes) of severe hypoglycemia
3. Known self or family history (first-degree relative) of multiple endocrine neoplasia Type 1.
4. Use of diabetes medications except insulin within 2 months prior to screening.
5. Any significant cardiovascular disease or QTcF prolongation within the last 6 months prior to screening.
6. Participants with fasting triglyceride ≥500 mg/dL.
7. Have an eGFR \<60 mL/min/1.73 m2 by the CKDEPI Creatinine Equation at screening.
8. Impaired liver function, defined as screening AST or ALT \>1.5 × ULN, Total bilirubin \>1.5 × ULN with the exception of Gilbert's Syndrome.
9. History of acute or chronic pancreatitis, complete pancreatectomy or pancreas transplants.
10. Serum lipase and/or amylase above 1.5 x ULN.
11. Known positive test for HIV, HBV surface antigen and COVID-19.
12. 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.
13. Active (symptomatic) celiac disease.
14. History of stomach or intestinal surgery that would potentially alter absorption and/or excretion of orally administered drugs.
15. History of cirrhosis.
16. Currently participating in a formal weight loss program and/or are currently using any drugs for weight management within 2 months of screening.
17. Use of Proton pump inhibitors (PPIs) is prohibited.
18. Treatment with a moderate or strong CYP3A4 inhibitor, inducer, or substrate within a week prior to dosing on Day 1.

Primary outcomes:
measure: To assess the effect on endogenous insulin secretion
timeFrame: 26 Weeks
Secondary outcomes:
measure: To assess the effect on endogenous insulin secretion
timeFrame: 26 Weeks
measure: To assess the effect on additional glycemic parameters
timeFrame: 26 Weeks of treatment
measure: To assess the effect on additional glycemic parameters
timeFrame: 26 Weeks
measure: To assess hypoglycemia events
timeFrame: 26 weeks
measure: To assess the effect on insulin doses
timeFrame: 26 Weeks
measure: Rate of symptomatic hypoglycemic episodes
timeFrame: 26 Weeks and during study duration
measure: Incidence of adverse events
timeFrame: 26 Weeks and during study duration
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: Sutter Valley Medical Foundation Pediatric Endocrinology
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research,Inc
state: California
city: Fort Myers
country: United States
facility: Southwest General Healthcare Center
state: Florida
city: New Port Richey
country: United States
facility: Suncoast Clinical Research, Inc.
state: Florida
city: North Miami Beach
country: United States
facility: Oceanic Research Group
state: Florida
city: West Palm Beach
country: United States
facility: Metabolic Research Institute
state: Florida
city: Atlanta
country: United States
facility: Atlanta Diabetes Associates
state: Georgia
city: Columbus
country: United States
facility: Centricity Research
state: Georgia
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Las Vegas
country: United States
facility: Palm Research Center
state: Nevada
city: Morehead City
country: United States
facility: Lucas Research, Inc.
state: North Carolina
city: Wilmington
country: United States
facility: Accellacare of Wilmington
state: North Carolina
city: Winston-Salem
country: United States
facility: Diabetes and Endocrinology Center
state: North Carolina
city: Norman
country: United States
facility: Alliance for Multispecialty Research
state: Oklahoma
city: Chattanooga
country: United States
facility: University Diabetes & Endocrine Consultants
state: Tennessee
city: Dallas
country: United States
facility: Velocity Clinical Research
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Diabetes and Thyroid Center of Fort Worth
state: Texas
city: Houston
country: United States
facility: PlanIt Research, PLLC
state: Texas
city: McKinney
country: United States
facility: Tekton Research
state: Texas
city: Round Rock
country: United States
facility: Texas Diabetes & Endocrinology
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas
state: Texas
city: San Antonio
country: United States
facility: Diabetes & Glandular Disease Clinic, P.A.
state: Texas
city: San Antonio
country: United States
facility: Endeavor Clinical Trials, LLC
state: Texas
city: Shavano Park
country: United States
facility: Consano Clinical Research, LLC
state: Texas
city: Manassas
country: United States
facility: Manassas Clinical Research Center
state: Virginia
city: Vancouver
country: Canada
facility: BC Diabetes
state: British Columbia
city: Brampton
country: Canada
facility: Centricity Research
state: Ontario
city: Ottawa
country: Canada
facility: Centricity Research
state: Ontario
city: Toronto
country: Canada
facility: Centricity Research
state: Ontario
Study officials:
affiliation: Biomea Fusion Inc.
name: Juan Pablo Frias, MD
role: STUDY_DIRECTOR
References: