Safety Evaluation of Gene Therapy Drug in the Treatment of Primary Hypertriglyceridemic Patients With Recurrent Pancreatitis

NCT05860569 | Recruiting Phase 1 DMC

• 1 other identifier: JL-GC304-01
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The study will evaluate safety and tolerance of intravenous delivery of GC304 gene therapy drug as a treatment of primary hypertriglyceridemic patients with previous onset of acute pancreatitis.

Conditions

Hypertriglyceridemia, Familial

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])

  Frequency of treatment-related adverse events (AEs), serious adverse events (SAEs), and changes from baseline in relevant clinical laboratory tests

  12 weeks

• The incidence of dose limited tolerance (DLT)

  12 weeks

Secondary Outcomes (5)

• Changes of plasma triglyceride levels from baseline

  12 weeks

• The proportion of patients who stop using lipid-lowering medications;

  12 weeks

• Copy numbers of viral vector DNA [Shedding of viral vectors];

  12 weeks

• Titers of antibody against viral vector

  12 weeks

• Titers of antibody against LPL (lipoprotein lipase) protein

  12 weeks

Other Outcomes (4)

• Changes of LPL activity in post-heparin plasma from baseline;

  52 weeks

• Frequency of onset of acute pancreatitis after administration of GC304;

  52 weeks

• Changes of plasma triglyceride levels from baseline；

  52 weeks

Study Arms (3)

Cohort 1

EXPERIMENTAL

3.0x10\^12 vg/kg of GC304 delivered one-time intravenously (n=3)

Genetic: GC304

Cohort 2

EXPERIMENTAL

1.0x10\^13 vg/ kg of GC304 delivered one-time i intravenously (n=3)

Genetic: GC304

Cohort 3

EXPERIMENTAL

3.0x10\^13 vg/ kg of GC304 delivered one-time i intravenously (n=3)

Genetic: GC304

Interventions

GC304 GENETIC

Self-complementary adeno-associated virus serotype 5 (AAV5) carrying a codon-optimized LPL coding sequence(coLPL) driven by a liver-specific promoter (LP)

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosed as primary hypertriglyceridemia poorly managed by regular treatment and dietary control, with episode of acute pancreatitis twice or once of severe acute pancreatitis within 5 years;
• Fasting plasma triglycerides (TG) levels above 5.65 mmol/L (intake of dietary fat \<30 g within 24 hours before blood taken);
• Homozygous or heterozygous mutations in GPIHBP1 or LPL genes by genetic screening;
• The patients within reproductive age take effective contraceptive measures voluntarily entering screening stage until 6 months after the trial;
• The patients fully understand and are able to comply with the requirements of the treatment and are willing to complete the trial as planned, including voluntary compliance with the trial procedures, acceptance of low-fat dietary requirements, and provide of biological samples.
• Be able to understand the procedures and methods of the trial and voluntarily participate with the signature of the informed consent by the patient or his/her guardian.

You may not qualify if:

• Patient who is known to be allergic to any ingredient of a trial drug (including immunosuppressants) or has any disease prohibited from the treatment;
• Patient who is having active bacteria, fungi, viruses or other infections;
• Patient who is intolerant of immunosuppressive drugs or steroids;
• Patient who is with any of the following clinical history of serious illness or existing serious illness:
• unrelieved abdominal pain caused by acute onset of pancreatitis or by other causes；
• disease history of malignancy or currently suffering from any malignant tumor;
• autoimmune diseases;
• disease history of epilepsy or mental illness (e.g. schizophrenia, depression, mania, anxiety, etc.);
• heart diseases: cardiomyopathy and myocarditis; structural heart diseases; coronary heart disease (acute coronary syndrome, myocardial infarction); pericardial disease; severe arrhythmias (severe tachycardia requiring pacemakers, severe rapid arrhythmias, and other arrhythmias beyond the control of medications) ; New York Heart Association (NYHA) classification heart function grading ≥III or Left Ventricular Ejection Fraction (LVEF) ≤50%;
• poorly controlled diabetes (fasting blood glucose ≥11.1mmol/L);
• with systolic blood pressure (SBP) \> 150mmHg and/or diastolic blood pressure (DBP) \> 100mmHg after treatment with a stable dose (at least 4 weeks) of antihypertensive drugs;
• The results of the laboratory examination at screening meet either of the following:
• Aspartate transaminase (AST) or alanine transaminase (ALT) \> 2 × upper limit of normals (ULN);
• Total bilirubin \> upper limit of normals (ULN);
• Creatinine \> upper limit of normals (ULN);

Sponsors & Collaborators

• GeneCradle Inc: lead

Study Sites (1)

Peking Union Medical College

Beijing, Beijing Municipality, China

RECRUITING

MeSH Terms

Conditions

Hyperlipoproteinemia Type IV

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Hypertriglyceridemia

Central Study Contacts

GeneCradle, Inc. China

CONTACT

86-13501380583; ind@bj-genecradle.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2023
• First Posted: May 16, 2023
• Study Start: September 20, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028
• Last Updated: July 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)