Study of MAR001 in Adults With Elevated Triglycerides and Remnant Cholesterol

Phase 2b Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study of MAR001 in Patients With Elevated Triglycerides and Remnant Cholesterol (TYDAL-TIMI 78)

The primary objective of the study is to evaluate the effect of MAR001 compared to placebo on levels of TG in adults with elevated TG and RC.

MAR-103 is a randomized, double-blind, parallel-group, placebo-controlled study with two parts (Part A and Part B).

In both Part A and Part B, participants will be randomized at Day 1. The study will include a screening period (up to 8 weeks), a 24-week treatment period, and a 12-week safety follow-up period. The 12-week safety follow-up period will include 2 clinic visits at Week 28 and Week 36 (End of Study).

Part A: Approximately 216 participants with baseline TG between 150 to 880 mg/dL will be enrolled in Part A at a 3:1 ratio of MAR001 to placebo for dosing every 4 weeks (Q4W). Three doses of MAR001 will be administered.

Part B: Approximately 100 participants with baseline TG between 450 and 2000 mg/dL will be enrolled in Part B at a 1:1 ratio of MAR001 to placebo for dosing every 4 weeks (Q4W). The MAR001 dose will be within the range tested during Part A and will be selected based on emerging Part A data.

Inclusion Criteria:

• Elevated fasting TGs and RC
• Elevated nonfasting TGs and RC
• Part A only: Fasting LDL-C ≥ 50 mg/dL (≥ 1.29 mmol/L) and ≤ 130 mg/dL (≤ 3.36 mmol/L)
• Willingness to provide informed consent and comply with the intervention and all study assessments
• Stable diet for a minimum of 3 months prior to screening and with no plans to change during screening or trial participation
• Stable drug regimen (if relevant) prior to screening visit and no planned changes after enrollment; Part B only: adjustment of lipid-lowering therapy during the diet/lifestyle run-in period is permitted

Exclusion Criteria:

• Acute or chronic liver disease

• Part A only: TG concentration ≥880mg/dl; Part B only: TG concentration ≥2000 mg/dL

• History of type 1 diabetes mellitus or history of diabetic ketoacidosis

• Newly diagnosed T2DM

• Participants with known active hepatitis A, B, or C

• Uncontrolled hypothyroidism

  • Part B only: recent history of active pancreatitis

    • Part B only: genetically confirmed Familial Chylomicronemia Syndrome (FCS) diagnosis due to biallelic loss of function mutations in LPL or GPIHBP1
    • Part B only: use of ANGPTL3 and ApoC-III inhibitors

• Any condition that prevents the participant from complying with study procedures