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NCT05043181

PHASE1

Exosome-based Nanoplatform for Ldlr mRNA Delivery in FH

Sponsor: Tang-Du Hospital

View on ClinicalTrials.gov

Summary

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.

Official title: Exosome-based Nanoplatform for Ldlr mRNA Delivery in Familial Hypercholesterolemia

Key Details

Gender

All

Age Range

18 Years - 45 Years

Study Type

INTERVENTIONAL

Enrollment

Start Date

2021-12

Completion Date

2026-12

Last Updated

2021-09-14

Healthy Volunteers

Conditions

Familial Hypercholesterolemia

Interventions

BIOLOGICAL

Low Density Lipoprotein Receptor mRNA Exosomes

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.

Inclusion Criteria: 1. Age 18-45, no gender limitation; 2. Patients with homozygous familial hypercholesterolemia diagnosed by genetic testing. 3. Understand the study and be willing to participate in the study with the informed consent signed Exclusion Criteria: 1. 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. 2. those who previously received targeted drug therapy, cell therapy, gene therapy or others immunotherapy; 3. those who had organ transplants in the past; 4. 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%. 5. those who are known or expected to have an allergic reaction to or have a history of allergic reaction to any of the ingredients treated by this test; 6. those who have a history of contrast agent allergic; 7. those who have a clear history of mental disorders in the past; 8. those who have a history of drug abuse or drug use; 9. Pregnant or lactating women; 10. Women of childbearing age and fertile men cannot take effective and adequate contraceptive measures (such as intrauterine device (IUD), condom, spermicidal gel plus condom, uterine cap, etc.) during the period of receiving the study drug and 3 months after the end of the study; 11. those who participated in the clinical study of other drugs within 3 months before joining the group; 12. Subjects that are not suitable to participate in this study for other reasons judged by the investigators.

Locations (1)

Tangdu Hospital, Air Force Medical University

Xi'an, Shannxi, China