Health TrialsbyHealthPanel

Exosome-based Nanoplatform for Ldlr mRNA Delivery in FH

ConditionFamilial Hypercholesterolemia
Trial statusNot yet recruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-45
SponsorTang-Du Hospital

About this trial

mRNA therapy is a highly promising gene therapeutic strategy in the treatment of Homozygous Familial Hypercholesterolemia (HoFH). Exosomes is safe and efficient carriers for mRNA drug delivery, due to their biocompatibility, bioavailability. This first-in-human study is aimed to evaluate the safety and preliminary effectiveness of Exosome-based ldlr mRNA nanoplatform for gene therapy in HoFH.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age 18-45, no gender limitation;

Patients with homozygous familial hypercholesterolemia diagnosed by genetic testing.

Understand the study and be willing to participate in the study with the informed consent signed

Disqualifiers

those who have severe comorbidities, including any of the following: A) unstable angina pectoris and/or congestive heart failure requiring hospitalization; B) myocardial infarction or cerebrovascular accident within the last 6 months; C) chronic obstructive pulmonary disease worsens or requires hospitalization; D) serious diseases of vascular, nervous system, blood, gastrointestinal and endocrine systems or metabolic disorders; E) autoimmune/immune deficiency diseases such as rheumatoid arthritis, acquired immune deficiency syndrome, and so on; F) malignant tumor or other chronic infection.

those who previously received targeted drug therapy, cell therapy, gene therapy or others immunotherapy;

those who had organ transplants in the past;

any of the following abnormalities are found in the laboratory examination: A) blood routine examination: absolute neutrophil count (ANC) < 1.5×109/L, or platelet (PLT) < 50×109/L, or hemoglobin (HGB) < 80 g/dL; B) coagulation function: prothrombin time (PT), or activated partial thrombin time (APTT), or INR > 1.5×ULN; C) liver function: total bilirubin (TBIL) > 2×ULN (upper limit of normal value), or alanine transferase (ALT), aspartate transferase (AST), alkaline phosphatase (ALP) > 5×ULN; D) renal function: serum creatinine (Cr) ≥1.5×ULN, or glomerular filtration rate (GFR) < 60 mL/min·1.73m2; E) cardiac ultrasound: left ventricular ejection fraction (LVEF) < 50%.

Trial design

Design model

Single group

Treatments tested in this trial

  • Low Density Lipoprotein Receptor mRNA Exosomes

    Biological/Vaccine

    The study consists of two phases: dose escalation phase and extension phase. Dose escalation phase：For the intervention of low-density lipoprotein receptor mRNA (LDLR mRNA) exosomes. A total of six dose groups are planned, with single dose of 0.044 mg/kg, 0.088 mg/kg, 0.145 mg/kg, 0.220 mg/kg, 0.295 mg/kg and 0.394 mg/kg, respectively. About 3 subjects are enrolled in each dose group. In the 0.044 mg/kg group, the second and third subjects are required to start exosome infusion treatment after the treatment of the previous subjects, and the other dose groups are not required to do this. There are three treatments in total, and the interval between each exosome treatment is 7±1 d. Extension phase: About 12 subjects are further enrolled. The subjects will receive 3 intravenous/peritoneal infusion treatment of LDLR mRNA exosomes once a week for three weeks, whose single dose is determined in the dose escalation phase.

Treatment groups

30 Participants
are divided into 1 treatment group
Group A: Homozygous Familial HypercholesterolemiaExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Changes of Total Cholesterol

mmol/L

Time frame
Changes from Baseline Total Cholesterol at Day 19
2

Changes of Low-Density Lipoprotein Cholesterol

mmol/L

Time frame
Changes from Baseline Low-Density Lipoprotein Cholesterol at Day 19
3

Changes of High-Density Lipoprotein Cholesterol

mmol/L

Time frame
Changes from Baseline High-Density Lipoprotein Cholesterol at Day 19
4

Changes of Triglyceride

mmol/L

Time frame
Changes from Baseline Triglyceride at Day 19

Secondary outcomes

1

Changes of Degree of Coronary Stenosis

% determined by coronary CT

Time frame
Changes from Baseline Degree of Coronary Stenosis at Day 28
2

Changes of Volume of Carotid Artery Plaques

cm3 determined by ultrasound

Time frame
Changes from Baseline Volume of Carotid Artery Plaques at Day 28
3

Changes of Stability of Carotid Artery Plaques

Grade I, II, III determined by ultrasound

Time frame
Changes from Baseline Stability of Carotid Artery Plaques at Day 28

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Tang-Du Hospital

Lead sponsor

Air Force Military Medical University, China

Collaborator

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: