Table 3.
Clinical Trials Investigating Human Gene Therapy for Ocular Angiogenesis Diseases Based on Ocular Injection of Non-coding RNA Interference Molecules
| Conditions | Identifier: ClinicalTrials.gov | Development Status | Drug | Vector | Mechanism | Route | Company | Study Start Date | Outcome |
|---|---|---|---|---|---|---|---|---|---|
| DME | NCT01445899 | phase II: completed | PF-04523655 | siRNA | siRNA targeting hypoxia-inducible gene RTP801 | IVT | Quark | February 2012 | evaluated the effect of PF-04523655 with/without ranibizumab in DME; no study results posted |
| nAMD | NCT00713518 | phase II: completed | PF-04523655 | siRNA | siRNA targeting hypoxia-inducible gene RTP801 | IVT | Quark/Pfizer | November 2009 | PF-04523655 monotherapy did not improve AMD as compared with ranibizumab monotherapy; combination of PF-04523655 with ranibizumab provided a synergic therapeutic benefit in visual acuity141 |
| nAMD | NCT00557791 | phase III: withdrawn | bevasiranib (Cand5) | siRNA | siRNA against VEGF | IVT | OPKO Health | November 2009 | study not initiated |
| DME | NCT00701181 | phase II: terminated | PF-04523655 | siRNA | siRNA targeting hypoxia-inducible gene RTP801 | IVT | Quark/Pfizer | June 2008 | a dose-dependent improvement in VA was observed in PF-04523655 therapy compared with laser treatment; the study was terminated due to an unexpectedly high discontinuation rate142 |
| nAMD | NCT00499590 | phase III: terminated | bevasiranib (Cand5) | siRNA | siRNA against VEGF | IVT | OPKO Health | August 2007 | bevasiranib-ranibizumab combination therapy showed a possible benefit for AMD, but the trial was unlikely to meet its primary endpoint and was terminated |
| nAMD | NCT00725686 | phase I: completed | PF-04523655 | siRNA | siRNA targeting hypoxia-inducible gene RTP801 | IVT | Quark/Pfizer | February 2007 | intravitreal injection with PF-04523655 appeared to be tolerable and safe143 |
| nAMD | NCT00395057 | phase II: terminated | AGN211745 (Sirna-027) | siRNA | siRNA targeting VEGFR-1 mRNA | IVT | Allergan | January 2007 | failed to meet therapeutic criteria |
| DME | NCT00306904 | phase II: completed | bevasiranib (Cand5) | siRNA | siRNA against VEGF | IVT | OPKO Health | January 2006 | an improved anatomic outcome and stabilization in VA were observed within 4 months |
| nAMD | NCT00259753 | phase II: completed | bevasiranib (Cand5) | siRNA | siRNA against VEGF | IVT | OPKO Health | July 2005 | bevasiranib-treated patients showed vision loss and increased lesion size, suggesting an insufficient efficacy with bevasiranib monotherapy |
| nAMD | NCT00363714 | phase I/II: completed | AGN211745 (Sirna-027) | siRNA | siRNA targeting VEGFR-1 mRNA | IVT | Allergan | November 2004 | AGN211745 was well tolerated in patients; stabilization or improvement in visual acuity and retinal structure was observed144 |
| nAMD | NCT00722384 | phase I: completed | bevasiranib (Cand5) | siRNA | siRNA against VEGF | IVT | OPKO Health | August 2004 | the safety data of five dosing groups was encouraging |
DME, diabetic macular edema; siRNA, small interfering RNA; IVT, intravitreal injection; nAMD, neovascular age-related macular degeneration; VA, visual acuity.