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

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase III Trial to Evaluate the Efficacy and Safety of DR10624 in Subjects With Severe Hypertriglyceridemia Receiving Stable Lipid-Modifying Therapy

This is a multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical trial to assess the efficacy and safety of weekly subcutaneous DR10624 injection in adult patients with severe hypertriglyceridemia (sHTG). Eligible participants have persistently elevated fasting triglycerides despite stable background lipid-lowering therapy. Subjects will be randomized at a 2:2:1 ratio to three treatment arms: DR10624 low dose, DR10624 high dose, or matching placebo, receiving weekly subcutaneous injections for a total of 64 weeks double-blind treatment, followed by a 4-week post-treatment safety follow-up. The primary goal is to evaluate the percentage reduction in fasting triglycerides at Week 26. Secondary assessments include changes in ApoC3, remnant cholesterol, liver fat content measured by MRI-PDFF, incidence of adjudicated acute pancreatitis, and overall safety profile including treatment-emergent adverse events and immunogenicity.

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.