TABLE 1.
Registered clinical trials of RNA-based therapy and gene therapy for RH (clinicaltrials.gov; search date: 2022/05/11).
| Indication | Title | Study type/CT phase | Therapeutic agent | Route of administration | Identifier | (Estimated) study start date–completion date |
|---|---|---|---|---|---|---|
| FH | Phase I Study of Ex Vivo Liver-Directed Gene Therapy for Familial Hypercholesterolemia | Interventional (Phase I) | autologous hepatocytes | Retrovirus LDL iv | NCT00004809 | June 1992–1995 |
| HyperTG, FH | Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS ANGPTL3-LRx in Healthy Volunteers With Elevated Triglycerides and Participants With Familial Hypercholesterolemia | Interventional (Phase I) | IONIS ANGPTL3-LRx | subcutaneous | NCT02709850 | 30 November 2015–26 June 2017 |
| HoFH | AAV8-mediated Low Density Lipoprotein Receptor (LDLR) Gene Replacement in Subjects With Homozygous Familial Hypercholesterolemia (HoFH) | Interventional (Phase I/II | AAV8-hLDLR | iv infusion | NCT02651675 | March 2016–27 November 2020 |
| HoFH | A Long-term Follow-up Study to Evaluate the Safety and Efficacy of RGX-501 | Observational | No investigational product, participants have previous received RGX-501(human LDLR Gene Therapy) | NCT04080050 | 30 September 2019–29 September 2025 | |
| HeFH, Elevated Cholesterol | Trial to Evaluate the Effect of Inclisiran Treatment on Low Density Lipoprotein Cholesterol (LDL-C) in Subjects With Heterozygous Familial Hypercholesterolemia (HeFH) (ORION-9) | Interventional (Phase III) | Inclisiran | SC injections | NCT03397121 | 28 November 2017–17 September 2019 |
| ASCVD, Elevated Cholesterol | Inclisiran for Participants With Atherosclerotic Cardiovascular Disease and Elevated Low-density Lipoprotein Cholesterol (ORION-10) | Interventional (Phase III) | Inclisiran | SC injections | NCT03399370 | 21 December 2017 - 17 September 2019 |
| ASCVD, ASCVD-Risk equivalents, Elevated Cholesterol | Inclisiran for Subjects With ASCVD or ASCVD-Risk Equivalents and Elevated Low-density Lipoprotein Cholesterol (ORION-11) | Interventional (Phase III) | Inclisiran | SC injections | NCT03400800 | 1 November 2017–27 August 2019 |
| HCL | A Non-interventional Implementation Study to Evaluate Treatment With Inclisiran (Leqvio®) and Other Lipid Lowering Treatments in a Real-world Setting | Observational | Inclisiran | SC injections | NCT05362903 | 28 January 2022–31 January 2025 |
| Dyslipidemias, FH, HyperTG | A Phase 1 Single and Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of ARO-ANG3 in Adult Healthy Volunteers and in Dyslipidemic Patients | Interventional (Phase I) | ARO-ANG3 | SC injections | NCT03747224 | 7 January 2019–17 May 2021 |
| Mixed Dyslipidemia | A Double-blind, Placebo-controlled Phase 2b Study to Evaluate the Efficacy and Safety of ARO-ANG3 in Adults With Mixed Dyslipidemia | Interventional (Phase II) | ARO-ANG3 | SC injections | NCT04832971 | 28 June 2021–30 April 2023 |
| HoFH | Phase 2 Study to Evaluate the Safety and Efficacy of ARO-ANG3 in Subjects With Homozygous Familial Hypercholesterolemia (HOFH) | Interventional (Phase II) | ARO-ANG3 | SC injections | NCT05217667 | June 2022–October 2023 |
| FH | Exosome-based Nanoplatform for Ldlr mRNA Delivery in Familial Hypercholesterolemia | Interventional (Phase I) | LDLR mRNA exosomes | Intravenous/peritoneal infusion | NCT05043181 | December 2021–December 2026 |
FH, familial hypercholesterolemia; HyperTG, hypertriglyceridemia; HoFH, homozygous familial hypercholesterolemia; HeFH, heterozygous familial hypercholesterolemia; ASCVD, atherosclerotic cardiovascular disease; HCL, hypercholesterolemia; SC, subcutaneous.