Severe Hypertriglyceridemia
Conditions
Brief summary
This is a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial for adults with severe hypertriglyceridemia whose lipid levels remain uncontrolled under standard Icosapent Ethyl background treatment plus lifestyle management. Eligible participants complete a screening run-in period, then randomize equally to three treatment groups: two active DR10624 subcutaneous injection groups and one placebo group. All subjects maintain fixed oral background lipid therapy throughout long-term double-blind treatment, followed by a short safety follow-up period. The primary objective is to evaluate the triglyceride-lowering effect of DR10624 versus placebo. Secondary assessments include other lipid indicators, liver fat content, overall safety, and anti-drug antibody status. Independent committees monitor interim data and adjudicate key clinical events to ensure participant safety.
Interventions
DRUGDR10624 Subcutaneous Injection
Weekly self-administered subcutaneous investigational biologic product, administered via autoinjector pen following standardized titration schedule throughout double-blind treatment phase.
Fixed daily oral omega-3 lipid-lowering background therapy, maintained at consistent stable dose for all participants across all three study arms for full trial duration.
Visually identical placebo autoinjector pen with inactive formulation, administered weekly following the identical titration timeline as active DR10624 groups to preserve double-blind status.
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. Age ≥18 years, male or female; BMI 19.0-45.0 kg/m², body weight ≥50 kg at screening. 2. Fasting triglyceride (TG) range 5.65-22.60 mmol/L: single screening lab result meets range, plus average of two separate fasting TG tests (interval \>1 week) within same range prior to randomization. 3. Stable lipid-lowering medications per local guidelines if on statin, cholesterol absorption inhibitor or PCSK9 inhibitor (minimum stable dose duration as required by drug class). 4. Females of childbearing potential agree effective contraception from ICF signing to 2 months post last dose; male participants agree contraception and no sperm donation for 3 months post last dose. 5. Able to understand study procedures, maintain consistent lifestyle and follow all protocol-specified requirements, and provide written informed consent.
Exclusion criteria
1. Confirmed hereditary lipid disorders (Fredrickson Type 1/3, Apo C-II deficiency). 2. Significant weight loss or planned weight reduction during study. 3. Severe chronic liver, renal or advanced cardiac disease. 4. Uncontrolled diabetes or hypertension with severe complications. 5. Pancreatitis history or symptomatic gallbladder disease. 6. Recent major cardiovascular, bone or thyroid disorders. 7. Severe psychiatric illness or substance abuse history. 8. Prior GLP-1/GCGR/FGF21 agonists or other investigational drugs within 3 months. 9. Abnormal screening lab parameters related to liver, pancreas, kidney or viral infection. 10. Pregnant, breastfeeding or hypersensitivity to study treatments. 11. Investigator's judgment of unsuitability for participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage change from baseline in average fasting serum triglyceride concentration at Week 26 | Baseline up to Week 26 of double-blind treatment period | Baseline TG defined as average value of Visit2, Visit3 and Visit4 fasting samples; Week26 TG defined as average of Week24 and Week26 fasting laboratory results; all participants receive continuous Icosapent ethyl 2g twice daily as background lipid-lowering treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage change from baseline in ApoC3 at Week 26 | Baseline to Week 26 of double-blind treatment | Fasting serum ApoC3 levels are measured via central laboratory validated biochemical assay. Percent change from baseline will be evaluated at Week 26 in subjects on stable twice-daily 2 g icosapent ethyl background lipid-lowering therapy throughout double-blind treatment. |
| Percent change from baseline LFC measured by MRI-PDFF Week26 | Baseline and Week 26 | Liver fat content is measured via centralized standardized MRI-PDFF scanning at baseline and Week 26. All scans are read by a blinded central imaging core laboratory. Subjects maintain stable twice-daily 2 g icosapent ethyl background lipid-lowering therapy during double-blind treatment. Relative percent change in LFC from baseline will be evaluated at Week 26. |
| Cumulative incidence of adjudicated acute pancreatitis up to Week 64 | Randomization through Week 64 double-blind treatment period | All suspected acute pancreatitis cases are fully adjudicated by an independent Event Adjudication Committee (EAC) per pre-specified diagnostic criteria throughout the 64-week double-blind treatment phase. Cumulative proportion of participants with confirmed adjudicated acute pancreatitis will be summarized from randomization to Week 64. |
| Proportion of participants with treatment-emergent adverse events (TEAEs) throughout the study | First study drug injection through 4-week post-treatment safety follow-up | All adverse events emerging from the first study drug injection until 4 weeks after the last injection are captured, coded by MedDRA and graded per pre-defined severity criteria. The percentage of participants experiencing any TEAE and the distribution of maximum TEAE severity will be summarized for the full safety observation window. |
| Percentage change from baseline in TRL-C at Week 26 | Baseline to Week 26 of double-blind treatment | Fasting serum samples for remnant cholesterol testing are analyzed by a validated central clinical laboratory. Percent change from baseline in TRL-C concentration will be assessed at Week 26 in participants with severe hypertriglyceridemia on stable twice-daily 2 g icosapent ethyl background therapy. |
Countries
China
Contacts
CONTACTYongliang Fang
STUDY_CHAIRJianping Li
Peking University First Hospital
STUDY_CHAIRLinong Ji
Peking University People's Hospital
Outcome results
None listed