Table 4.
Overview of Hemophilia B Clinical Studies Based on Liver-Directed Gene Transfer
| Sponsor | Phase | Study ID: ClinicalTrials.gov | Product | Dose (vg/kg) | Immune Responses | References |
|---|---|---|---|---|---|---|
| Avigen | I/II | NCT00076557 | ssAAV2-LP1-FIX | 8 × 1010 (n = 2) | pre-existing NAbs; dose-dependent cellular responses to the capsid and elevation of liver transaminases | 32 |
| 4 × 1011 (n = 3) | ||||||
| 2 × 1012 (n = 2) | ||||||
| St. Jude Children’s Research Hospital | I | NCT00979238 | scAAV8-LP1-FIXco | 2 × 1011 (n = 2) | anti-capsid cellular responses; elevation of liver transaminases in four patients resolved with prednisolone | 5,63 |
| 6 × 1011 (n = 2) | ||||||
| 2 × 1012 (n = 6) | ||||||
| Baxalta/ Shire | I/II | NCT01687608 | scAAV8-TTR-FIXR338Lopt (AskBio009, BAX 335) | 2 × 1011 (n = 2) | dose-dependent T cell responses and elevation of liver transaminases in two patients resolved with prednisolone | 176,177 |
| 1 × 1012 (n = 4) | ||||||
| 3 × 1012 (n = 2) | ||||||
| UniQure | I/II | NCT02396342 | scAAV5-hAAT-FIX (AMT-060) | 5 × 1012 (n = 5) | elevation of liver transaminases in three patients resolved with prednisolone | 178 |
| 2 × 1013 (n = 5) | ||||||
| UniQure | IIb | NCT03489291 | scAAV5-hAAT-FIXPadua (AMT-061, etranacogene dezaparvovec) | 2 × 1013 (n = 3) | pre-existing NAbs; no significant inflammatory responses | 179 |
| Pfizer | I/II | NCT02484092 | SPK-9001 | 5 × 1011 (n = 15) | elevation of liver transaminases in two patients resolved with prednisolone | 62,180 |
| Dimension Therapeu-tics | I/II | NCT02618915 | ssAAVrh10-FIX (DTX101) | 1.6 × 1012 (n = 3) | elevation of liver transaminases treated with prednisolone | 181 |
| 5 × 1012 (n = 3) |