Table 1.
Clinical Trial Results for AAV-Mediated Gene Therapy for Factor IX Deficiency
| Vector Product | NCT | Trial Phase | Vector Dose | Number Treated | FIX (%) at Year: 0.5–1y | 1.5–2y | 2.5–3y | 4y | 5y | 6y | Transaminitis Rate | Reference |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CHOP/Avigen | ||||||||||||
| rAAV2-FIX (intramuscular) | 1 | 0.2 to 1.8 ×1012 | 8 | 0 | [11,12] | |||||||
| CHOP/Avigen | ||||||||||||
| rAAV2-FIX-WT (intra-hepatic artery) | NCT00515710 | 1/2 | 0.08 to 2×1012 | 7 | 0 | [13] | ||||||
| St. Jude/UCL | ||||||||||||
| rAAV8-FIX-WT | NCT00979238 | 1/2 | 2×1012 | 6 | 1.4–7.2 | 5.1±1.7 | 5.1 | 4/6 (67%) | [15–17] | |||
| Uniqure/CSL Behring | ||||||||||||
| AMT060, rAAV5-FIX-WT | NCT02396342 | 1 | 2×1013 | 5 | 6.9 (2.6–11.3) | 7.1 | 8.4 | 7.4 | 5.2 | 2/5 (40%) | [19,20] | |
| AMT061, (etranacogene dezaparvovec, rAAV5-FIX-R338L) | NCT03489291 | 2 | 2×1013 | 3 | 47 (33–57) | 50 (37.1–58.6) | 0/0 (0%) | [21] | ||||
| NCT03569891 | 3 | 2×1013 | 54 | 39±18.7 (8.2–97.1) | 36.9±21.4 (4.5–122.9) | 0/0 (0%) | [22] | |||||
| Pfizer/Spark | ||||||||||||
| SPK9001, (fidanacogene elaparvovec, SPK100-FIX-R388L) | NCT02484092 | 2 | 5×1011 | 15 | 22.9±9.9 | 3/15 (20%) | [23,24] | |||||
| NCT03861273 | 3 | n/a | n/a | |||||||||
| UCL/Freeline | ||||||||||||
| FLT180a, (AAVS3-FIX-R388L) | NCT03369444 | 1 | 8.3×1011 | 4 | 50–180 | n/a | [25] | |||||
| NCT05164471 | 1/2 | 7.7×1011 | 1 | n/a | ||||||||
| IHBDH/SBDB | ||||||||||||
| BBM-H901, AAV843-FIX-WT | NCT04135300 | 1/2 | 5×1012 | 10 | n/a | |||||||
| HBDH/FIX Variant | ||||||||||||
| VGB-R0-4 | NCT05152732 | 2 | n/a | n/a | n/a | |||||||
| Dimension/Ultragenics | ||||||||||||
| DTX101, AAVrh10-FIX-WT | NCT02718915 | 1 | 5×1012 | 3 | 0 | n/a | [27] | |||||
| Baxalta/Takeda | ||||||||||||
| BAX335, rAAV8-FIX-R388L | NCT01687608 | 1 | 3×1012 | 2 | 45.3 (32–59) | 20 (n=1) | n/a | [26] | ||||
| Takeda/Baxalta/Shire | ||||||||||||
| SHP648, rAAV8-FIX-R388L | NCT04394286 | 1 | n/a | |||||||||