Phase 2 Trial of BMF-219 in Participants with Type 1 Diabetes Mellitus

Biomea Fusion

Status and phase: Active, not recruiting; Phase 2

Conditions: Type 1 Diabetes Mellitus

Treatments: Drug: BMF-219

Study type: Interventional

Funder types: Industry

Identifiers

NCT06152042

COVALENT-112

Details and patient eligibility

About

Phase 2 Trial of BMF-219 in Participants with Type 1 Diabetes Mellitus.

Full 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.

Enrollment: 190 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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190 participants in 3 patient groups, including a placebo group

Part 1

Experimental group

Description:

Part 1 uses a randomized, open-label design with parallel assignment between 2 treatment arms in each cohort. The Part 1 Eligible participants will be randomly assigned by cohort to 1 of 2 treatment arms: * Cohort 1: Participants with T1D diagnosed within 3 years with C-peptide concentration ≥0.2 nmol/L * Arm A: BMF-219 100 mg QD for 12 weeks * Arm B: BMF-219 200 mg QD for 12 weeks * Cohort 2: Participants with T1D diagnosed between 3 to 15 years with C-peptide concentration ≥0.08 nmol/L. * Arm A: BMF-219 100 mg QD for 12 weeks * Arm B: BMF-219 200 mg QD for 12 weeks

Treatment:

Drug: BMF-219

Part 2

Experimental group

Description:

Part 2 Part 2 uses a randomized, double-blind, placebo-controlled design with parallel assignment among 3 treatment arms. Eligible participants will be randomly assigned to 1 of 3 arms using a 1:1:1 ratio: * Arm A: BMF-219 100 mg QD for 12 weeks * Arm B: BMF-219 200 mg QD for 12 weeks

Treatment:

Drug: BMF-219

Placebo Comparator

Placebo Comparator group

Description:

Part 2 Study Double Blind Arm C matching placebo for 12 weeks.

Treatment:

Drug: BMF-219