A Phase III Study to Evaluate the Efficacy and Safety of of DR10624 in Subjects With Severe Hypertriglyceridemia

• DR10624 Injection (Biological): Novel investigational biologic agent for severe hypertriglyceridemia, administered via weekly subcutaneous injection with two titrated dose regimens (low-dose and high-dose) for 64 weeks double-blind treatment period.
• Matching Placebo for DR10624 (Other): Volume-matched inert subcutaneous injection placebo, visually identical to DR10624 to maintain double-blind masking for all study participants.

Primary outcomes

• Percentage change from baseline in central laboratory-measured fasting serum triglyceride at Week 26 [Baseline to Week 26 of double-blind treatment]

Secondary outcomes

• Percentage change from baseline in central laboratory-measured apolipoprotein C3 (ApoC3) at Week 26 [Baseline to Week 26 double-blind treatment]
• Percentage change from baseline in central laboratory-measured triglyceride-rich lipoprotein cholesterol (TRL-C) at Week 26 [Baseline to Week 26 double-blind treatment]
• Percentage change from baseline in central laboratory-measured non-high-density lipoprotein cholesterol (non-HDL-C) at Week 26 [Baseline to Week 26 double-blind treatment]
• Proportion of participants achieving fasting triglyceride <5.65 mmol/L at Week 26 [Week 26]
• Proportion of participants achieving fasting triglyceride <1.70 mmol/L at Week 26 [Week 26]
• Percentage change from baseline in liver fat content quantified by blinded central MRI-PDFF imaging at Week 26 [Baseline to Week 26 double-blind treatment]
• Cumulative proportion of participants with Event Adjudication Committee (EAC)-confirmed acute pancreatitis from randomization through Week 64 [Randomization through Week 64 double-blind treatment]
• Overall incidence and maximum severity grade of all treatment-emergent adverse events (TEAEs) [First study drug injection through 4-week post-treatment safety follow-up]

Other outcomes

• Absolute and percentage change from baseline in serum DR10624 concentration quantified by validated central laboratory bioanalytical assay [First study drug injection through 4-week post-treatment safety follow-up]

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. Male or female aged ≥18 years at screening.
2. BMI 19.0-45.0 kg/m², body weight ≥50.0 kg.
3. Fasting triglyceride meets protocol-specified threshold at local lab and average of two separate central lab fasting samples collected ≥1 week apart.
4. On stable guideline lipid-lowering therapy ≥4 weeks.
5. Able to follow protocol and maintain stable lifestyle; sign voluntary written informed consent.

Exclusion Criteria:

1. Confirmed/suspected familial severe hypertriglyceridemia subtypes (Fredrickson Type 1/3, ApoC-II deficiency).
2. Unstable body weight, severe liver/kidney disease, uncontrolled diabetes or hypertension, NYHA III-IV heart failure, Cushing syndrome.
3. History of acute pancreatitis within 6 months, chronic pancreatitis or symptomatic gallbladder disease.
4. Recent major cardiovascular events, bone disorders, abnormal thyroid function or active malignancy within 5 years.
5. Severe psychiatric disorders, substance abuse/excessive alcohol intake, or MTC/MEN2 family/personal history.
6. Prior exposure to GLP-1R/GCGR/FGF21R agonists, relevant investigational drugs or other interventional trials within 3 months.
7. Unqualified lab results at screening: abnormal liver/pancreas/renal indexes, elevated HbA1c, positive HIV/HBV/HCV, severe arrhythmia.
8. Pregnancy/lactation, contraception refusal, hypersensitivity to study drug, blood donation ≥400mL recently, or any conditions judged by investigator to affect trial safety/efficacy.

• Junbo Ge, Study chair, Shanghai Zhongshan Hospital