Table 3.
Clinical trial status of selected siRNA therapeutics
| Pathology/disease | Drug name | Delivery system | Mode of application | Target gene | Status/important past or ongoing studies | ClinicalTrials.gov identifier |
|---|---|---|---|---|---|---|
|
Primary hyperoxaluria type 1 Primary hyperoxaluria type 2 |
DCR-PHXC (Nedosiran) | GalNAc conjugate | s.c. | LDH | Phase III, enrolling by invitation (patients previously enrolled and their siblings; long-term safety and efficacy) | NCT04042402 |
| Children and adults with primary hyperoxaluria type 1 and 2 | Phase II (PHYOX2), completed | NCT03847909 | ||||
| Primary hyperoxaluria type 3 | Phase I, completed | NCT04555486 | ||||
| Paroxysmal nocturnal hemoglobinuria | Cemdisiran | GalNAc conjugate | s.c. | C5 | Phase I/II, completed | NCT02352493 |
| Paroxysmal nocturnal hemoglobinuria | Phase II, active, not recruiting | NCT03841448 | ||||
| Mild-to-moderate hypertension | ALN-AGT01 (Zilebesiran) | GalNAc conjugate | s.c. | AGT | Phase II (KARDIA-1), recruiting | NCT04936035 |
| Hypertension inadequately controlled by standard medicines | Phase II (KARDIA-2), recruiting | NCT05103332 | ||||
| Cardiovascular disease, patients with elevated serum lipoprotein A | AMG 890 (Olpasiran) |
GalNAc conjugate |
s.c. | Lipoprotein A | Phase I, recruiting | NCT03626662 |
| Phase II, active, not recruiting | NCT04270760 | |||||
| Phase I, active, not recruiting | NCT04987320 | |||||
| B-cell non-Hodgkin lymphoma, relapsed or refractory | CpG-STAT3 siRNA CAS3/SS3 | n.d. | Intratumoral + localized radiation therapy | CpG oligonucleotide (TLR9) + siSTAT3 | Phase I, recruiting | NCT04995536 |
| Advanced malignant solid neoplasms | siRNA-EphA2-DOPC | DOPC-encapsulated siRNA | i.v. | EphA2 | Phase I, recruiting | NCT01591356 |
| Metastatic pancreatic ductal adenocarcinoma with KrasG12D mutation | KRAS G12D siRNA | Mesenchymal stromal cell-derived exosomes | i.v. | KrasG12D | Phase I, recruiting | NCT03608631 |
| Pancreatic ductal adenocarcinoma | siG12D-LODER | LODER (Local Drug EluteR) | Local implantation + chemotherapy | KrasG12D | Phase II, recruiting | NCT01676259 |
| Local implantation | Phase I, completed | NCT01188785 | ||||
| Advanced solid tumors | Atu027 | siRNA-lipoplex/AtuPLEX | i.v. | PKN3 | Phase I, completed | NCT00938574 |
| Hepatocellular carcinoma | DCR-MYC | Lipid nanoparticle | i.v. | MYC | Phase I, terminated prematurely (sponsor decision) | NCT02314052 |
| Solid tumors, multiple myeloma, or non-Hodgkin lymphoma | Phase I, terminated prematurely (sponsor decision) | NCT02110563 | ||||
| Solid cancers with hepatic metastases | TKM-080301 | Lipid nanoparticles |
Hepatic intra-arterial |
PLK1 | Phase I, completed | NCT01437007 |
| Clear cell renal cell carcinoma | ARO-HIF2 | RGD-siRNA conjugate (TRiM) | i.v. | HIF2alpha | Phase I, recruiting | NCT04169711 |
| Cutaneous squamous cell carcinoma in situ (Bowen’s disease) | STP705 (Cotsiranib) | Nanoparticles with His-Lys co-polymer (HKP) peptide | Intralesional injection | TGF-β1 and Cox-2 |
Phase II, completed Phase II, recruiting |
|
| Basal cell carcinoma | Local injection | Phase II, recruiting | NCT04669808 | |||
| Hypertrophic scar | Intradermal | Phase II, completed | NCT02956317 | |||
| Intrascar | Phase I/II, not yet recruiting | NCT05196373 | ||||
| Reduction in post-keloidectomy keloid recurrence | Intradermal into the excised keloid site | Phase II, recruiting | NCT04844840 | |||
| Recurrent glioblastoma | NU-0129 | Spherical nucleic acid platform (= small spherical gold nanoparticles) | i.v. | Bcl2L12 | Phase I, completed | NCT03020017 |
| Prevention of hypertrophic scar | BMT101/cp-asiRNA | Cell-penetrating asymmetric siRNA | Intradermal injection | Phase IIa, recruiting | NCT04012099 | |
| Reducing recurrence of hypertrophic scar | OLX10010 | Cell penetrating asymmetric siRNA | Intradermal injection | Phase IIa, recruiting | NCT04877756 | |
| Elevated intraocular pressure | SYL040012 (Bamosiran) | n.d. | 1 drop in the affected eye | ADRbeta2 | Phase II, completed | NCT02250612 |
| Moderate-to-severe dry eye disease | SYL1001 (Tivanisiran) | Ophthalmic solution | 1 drop in the affected eye | TRPV1 | Phase III, completed | NCT03108664 |
|
Dry eye disease with Sjögren syndrome |
Phase III, recruiting | NCT04819269 | ||||
| Acute primary angle-closure glaucoma | QPI-1007 (Cosdosiran) | n.d. | Intravitreal injection | Caspase-2 | Phase IIa, completed | NCT01965106 |
| Nonarteritic anterior ischemic optic neuropathy | Phase IIb/III, terminated after interim analysis | NCT02341560 | ||||
| Diabetic macular edema, choroidal neovascularization, diabetic retinopathy | PF-04523655 | n.d. | With/without ranibizumab | RTP801 | Phase II, completed | NCT01445899 |
| Prevention of major adverse kidney events in subjects at high risk for AKI following cardiac surgery | QPI-1002 (Teprasiran) | n.d. | i.v. | P53 | Phase II, completed | NCT02610283 |
| Delayed graft function | Phase III, completed | NCT02610296 | ||||
| Gout | ALN-XDH |
GalNAc conjugate |
s.c. | Xanthine dehydrogenase | Phase I/II, recruiting | NCT05256810 |
| Thalassaemia or myelo-dysplastic syndrome | SLN124 |
GalNAc conjugate |
s.c. | TMPRSS6 | Phase I, recruiting | NCT04718844 |
| Nonalcoholic steatohepatitis | ALN-HSD | GalNAc conjugate | s.c. | HSD17B13 | Phase I, recruiting | NCT04565717 |
| Hepatitis B | ARO-HBV (JNJ-3989) | GalNAc conjugate | s.c. | HBV RNAs | Phase II, completed | NCT03365947 |
| Hepatitis B | DCR-HBVS (RG6346) | GalX | s.c., alone or in combination | HBsAg | Phase I, active, not recruiting | NCT03772249 |
| Hepatitis B | AB-729 | GalNAc conjugate | s.c. | Viral antigens | Phase II, active, not recruiting | NCT04820686 |
| Hepatitis D | Phase II, active, not recruiting | NCT04847440 | ||||
| COVID-19 (patients with symptomatic moderate COVID-19 not requiring intensive care) | MIR 19 (siR-7-EM/KK-46) | Peptide dendrimer KK-46 | Inhalation | RdRp | Phase II, completed | NCT05184127 |
| Hemophilia A and B | ALN-AT3SC (Fitusiran) | GalNAc conjugate | SERPINC1 | Phase III, active, not recruiting | NCT03549871 | |
| Phase I/II | NCT02554773 | |||||
| Phase III, completed | NCT03417102 | |||||
| Phase III, completed | NCT03417245 | |||||
| Phase I, completed | NCT02035605 | |||||
| Moderate-to-extensive hepatic fibrosis | ND-L02-s0201 | Vitamin A-coupled lipid nanoparticle | i.v. | HSP47 | Phase Ib/II, completed | NCT02227459 |
| Idiopathic pulmonary fibrosis | Phase II, active, not recruiting | NCT03538301 | ||||
| Dyslipidemic patients including familial hypercholesterolemia and severe hypertriglyceridemia | ARO-ANG3 |
GalNAc conjugate |
s.c. | ANGPTL3 | Phase I, completed | NCT03747224 |
| Mixed dyslipidemia | Phase II, recruiting | NCT04832971 | ||||
| Familial chylomicronemia syndrome | ARO-APOC3 |
GalNAc conjugate |
s.c. | ApoC3 | Phase III, recruiting | NCT05089084 |
| Severe hypertriglyceridemia | Phase II, recruiting | NCT04720534 | ||||
| Mixed dyslipidemia | Phase II, recruiting | NCT04998201 |
AKI acute kidney injury, COVID-19 coronavirus disease 2019, DOPC 1,2-dioleoyl-sn-glycero-3-phosphocholine, GalNAc N-acetylgalactosamine, i.v. intravenous, n.d. not defined, s.c. subcutaneous, siRNA small interfering RNA