Hypertriglyceridemia, Severe Hypertriglyceridemia (sHTG)
Conditions
Keywords
Severe hypertriglyceridemia, hypertriglyceridemia, triglyceride, Apolipoprotein C3, remnant cholesterol, nonalcoholic fatty liver disease, MRI-PDFF, acute pancreatitis, DR10624, subcutaneous injection, lipid lowering therapy, phase 3 clinical trial, investigational new drug, hyperlipidemia
Brief summary
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.
Interventions
BIOLOGICALDR10624 Injection
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.
OTHERMatching Placebo for DR10624
Volume-matched inert subcutaneous injection placebo, visually identical to DR10624 to maintain double-blind masking for all study participants.
Sponsors
Zhejiang Doer Biologics Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage change from baseline in central laboratory-measured fasting serum triglyceride at Week 26 | Baseline to Week 26 of double-blind treatment |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
China
Contacts
CONTACTYongliang Fang
STUDY_CHAIRJunbo Ge
Shanghai Zhongshan Hospital
Outcome results
None listed