Characteristics of included studies
| Trial name/NCT (phase) . | Gene therapy (prior names) . | Setting . | Design . | N∗ (n for individual dose cohorts) . | AAV vector . | Dose(s) (vg/kg) . | Age (y), mean (range) . | Non-White, % . | Duration (mo) . | Hemophilia severity (severe/moderately severe [%]) . | Time at which ABR measurement started . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| HA | |||||||||||
| Alta/NCT03061201 (1/2) | Giroctocogene fitelparvovec (PF-07055480/SB-525) | United States | Open-label, dose-escalation, cohort study | 11 | AAV6 | 9e11, 2e12, 1e13, 3e13 | 30 (18-47) | 18.2 | 62 | 100/0 | Week 3 |
| GENEr8-1/NCT02576795 (1/2) | Valoctocogene roxaparvovec (BMN-270) | United Kingdom | Open-label, dose-escalation, cohort study | 13 (7, 6) | AAV5 | 6e13 4e13 | 30.4 (23-42) 31.3 (22-45) | 14.3 16.7 | 72 | 100/0 | Week 4 |
| GENEr8-1/NCT03370913 (3) | Valoctocogene roxaparvovec (BMN-270) | 13 countries† | Open-label, single-arm, cohort study | 134 | AAV5 | 6e13 | 31.7 (18-70) | 28.4 | 36 | 100/0 | Week 5 |
| NCT03003533/NCT03432520 (1/2) | Dirloctogene samoparvovec (SPK-8011) | 5 countries‡ | Open-label, dose-escalation, cohort study | 24 | AAV3 | 5e11 1e12 1.5e12 2e12 | 32.8 (18-52) | NR | 60 | 94.4/5.6 | Week 4 |
| NCT03734588 (1/2) | SPK-8016 | United States | Open-label, single-arm, cohort study | 4 | AAV-Spark | 5e11 | (18-63) | NR | 15 | 100/0 | NR |
| NCT03370172 (1/2) | TAK-754 | 8 countries§ | Open-label, dose-escalation, cohort study | 4 | AAV8 | 2e12 6e12 | (18-75) | NR | 10 | 100/0 | NR |
| NCT03588299 (1/2) | BAY 2599023 (AAVhu37.hFVIIIco) | 6 countries|| | Open-label, dose-escalation, cohort study | 9 | AAVhu37 | 5e12, 1e13, 2e13, 4e13 | NR | NR | 23 | 100/0 | NR |
| NCT03001830GO-8 (1/2) | GO-8 (AAV8-HLP-hFVIII-V3) | United States, United Kingdom | Open-label, dose-escalation, cohort study | 12 (1, 3, 3, 5) | AAV8 | 6e11, 2e12, 4e12, 6e12 | NR | NR | 60 | 100/0 | NR |
| HB | |||||||||||
| BENEGENE-2/NCT02484092 (1/2) | Fidanacogene elaparvovec (SPK-9001) | United States, Australia | Open-label, single-arm, cohort study | 15 | AAV-Spark100 | 5e11 | 35.6 (18-53) | 14.3 | 12 | 60/40 | Day 0 |
| BENEGENE-2/NCT03861273 (3) | Fidanacogene elaparvovec (SPK-9001) | 14 countries¶ | Open-label, single-arm, cohort study | 45 | AAV-Spark100 | 5e11 | 29 (18-62) | NR | 15 | NR | Week 12 |
| B-LIEVE/NCT05164471 (1/2) | Verbrinacogene setparvovec (FLT180a) | United States, United Kingdom | Open-label, single-arm, cohort study | 6 | AAVS3 | 7.7e11 | NR | NR | 12 | NR | NR |
| B-AMAZE/NCT03369444 (1/2) | Verbrinacogene setparvovec (FLT180a) | United States, Ireland, Italy, United Kingdom | Open-label, dose-escalation, cohort study | 10 (2, 2, 4, 2) | AAVS3 | 3.84e11, 6.4e11, 8.32e11, 1.28e12 | 37.2 (25-67) | 10 | 27.2 | 90/10 | Day 15 |
| NCT02396342 (1/2) | AMT-060 | Denmark, Germany, The Netherlands | Open-label, dose-escalation, cohort study | 10 (5, 5) | AAV5 | 5e12 2e13 | 69 (35-72) 35 (33-46) | 0 20 | 60 | 80/20 100/0 | NR |
| HOPE-B/NCT03569891 (2b) | Etranacogene dezaparvovec (AMT-061) | United States | Open-label, single-arm, cohort study | 3 | AAV5 | 2e13 | 46.7 (43-50) | 66.7 | 36 | 66.7/33.3 | Day 0 |
| HOPE-B/NCT03569891 (3) | Etranacogene dezaparvovec (AMT-061) | 8 countries# | Open-label, single-arm, cohort study | 54 | AAV5 | 2e13 | 41.5 (19-75) | 25.9 | 26.5 | 81/19 | Month 7 |
| NCT01687608 (1/2) | BAX335 | United States | Open-label, dose-escalation, cohort study | 8 | AAV8 | 2e11, 1e12, 3e12 | 30.5 (20-69) | 12.5 | 86 | NR | NR |
| NCT00979238 (1) | scAAV2/8-LP1-hFIXco | United States, United Kingdom | Open-label, dose-escalation, cohort study | 10 | AAV8 | 2e11, 6e11, 2e12 | 36.3 (22-64) | NR | 128 | 100/0 | NR |
| 101HEMB01/NCT02618915 (1/2) | DTX101 | United States, Bulgaria, United Kingdom | Open-label, dose-escalation, cohort study | 6 (3, 3) | AAVrh10 | 1.6e12, 5e12 | (50-84, 18-49) | NR | 12 | NR | Day 0 |
| NCT04135300 (1) | BBM-H901 | China | Open-label, single-arm, cohort study | 10 | AAV843 | 5e12 | NR | 100 | 13 | NR | NR |
| NCT00515710 (1/2) | AAV2-hFIX16 | United States | Open-label, dose-escalation, cohort study | 7 | AAV2 | 8e10, 4e11, 2e12 | 34 (20-63) | NR | 180 | 100/0 | NR |
| Trial name/NCT (phase) . | Gene therapy (prior names) . | Setting . | Design . | N∗ (n for individual dose cohorts) . | AAV vector . | Dose(s) (vg/kg) . | Age (y), mean (range) . | Non-White, % . | Duration (mo) . | Hemophilia severity (severe/moderately severe [%]) . | Time at which ABR measurement started . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| HA | |||||||||||
| Alta/NCT03061201 (1/2) | Giroctocogene fitelparvovec (PF-07055480/SB-525) | United States | Open-label, dose-escalation, cohort study | 11 | AAV6 | 9e11, 2e12, 1e13, 3e13 | 30 (18-47) | 18.2 | 62 | 100/0 | Week 3 |
| GENEr8-1/NCT02576795 (1/2) | Valoctocogene roxaparvovec (BMN-270) | United Kingdom | Open-label, dose-escalation, cohort study | 13 (7, 6) | AAV5 | 6e13 4e13 | 30.4 (23-42) 31.3 (22-45) | 14.3 16.7 | 72 | 100/0 | Week 4 |
| GENEr8-1/NCT03370913 (3) | Valoctocogene roxaparvovec (BMN-270) | 13 countries† | Open-label, single-arm, cohort study | 134 | AAV5 | 6e13 | 31.7 (18-70) | 28.4 | 36 | 100/0 | Week 5 |
| NCT03003533/NCT03432520 (1/2) | Dirloctogene samoparvovec (SPK-8011) | 5 countries‡ | Open-label, dose-escalation, cohort study | 24 | AAV3 | 5e11 1e12 1.5e12 2e12 | 32.8 (18-52) | NR | 60 | 94.4/5.6 | Week 4 |
| NCT03734588 (1/2) | SPK-8016 | United States | Open-label, single-arm, cohort study | 4 | AAV-Spark | 5e11 | (18-63) | NR | 15 | 100/0 | NR |
| NCT03370172 (1/2) | TAK-754 | 8 countries§ | Open-label, dose-escalation, cohort study | 4 | AAV8 | 2e12 6e12 | (18-75) | NR | 10 | 100/0 | NR |
| NCT03588299 (1/2) | BAY 2599023 (AAVhu37.hFVIIIco) | 6 countries|| | Open-label, dose-escalation, cohort study | 9 | AAVhu37 | 5e12, 1e13, 2e13, 4e13 | NR | NR | 23 | 100/0 | NR |
| NCT03001830GO-8 (1/2) | GO-8 (AAV8-HLP-hFVIII-V3) | United States, United Kingdom | Open-label, dose-escalation, cohort study | 12 (1, 3, 3, 5) | AAV8 | 6e11, 2e12, 4e12, 6e12 | NR | NR | 60 | 100/0 | NR |
| HB | |||||||||||
| BENEGENE-2/NCT02484092 (1/2) | Fidanacogene elaparvovec (SPK-9001) | United States, Australia | Open-label, single-arm, cohort study | 15 | AAV-Spark100 | 5e11 | 35.6 (18-53) | 14.3 | 12 | 60/40 | Day 0 |
| BENEGENE-2/NCT03861273 (3) | Fidanacogene elaparvovec (SPK-9001) | 14 countries¶ | Open-label, single-arm, cohort study | 45 | AAV-Spark100 | 5e11 | 29 (18-62) | NR | 15 | NR | Week 12 |
| B-LIEVE/NCT05164471 (1/2) | Verbrinacogene setparvovec (FLT180a) | United States, United Kingdom | Open-label, single-arm, cohort study | 6 | AAVS3 | 7.7e11 | NR | NR | 12 | NR | NR |
| B-AMAZE/NCT03369444 (1/2) | Verbrinacogene setparvovec (FLT180a) | United States, Ireland, Italy, United Kingdom | Open-label, dose-escalation, cohort study | 10 (2, 2, 4, 2) | AAVS3 | 3.84e11, 6.4e11, 8.32e11, 1.28e12 | 37.2 (25-67) | 10 | 27.2 | 90/10 | Day 15 |
| NCT02396342 (1/2) | AMT-060 | Denmark, Germany, The Netherlands | Open-label, dose-escalation, cohort study | 10 (5, 5) | AAV5 | 5e12 2e13 | 69 (35-72) 35 (33-46) | 0 20 | 60 | 80/20 100/0 | NR |
| HOPE-B/NCT03569891 (2b) | Etranacogene dezaparvovec (AMT-061) | United States | Open-label, single-arm, cohort study | 3 | AAV5 | 2e13 | 46.7 (43-50) | 66.7 | 36 | 66.7/33.3 | Day 0 |
| HOPE-B/NCT03569891 (3) | Etranacogene dezaparvovec (AMT-061) | 8 countries# | Open-label, single-arm, cohort study | 54 | AAV5 | 2e13 | 41.5 (19-75) | 25.9 | 26.5 | 81/19 | Month 7 |
| NCT01687608 (1/2) | BAX335 | United States | Open-label, dose-escalation, cohort study | 8 | AAV8 | 2e11, 1e12, 3e12 | 30.5 (20-69) | 12.5 | 86 | NR | NR |
| NCT00979238 (1) | scAAV2/8-LP1-hFIXco | United States, United Kingdom | Open-label, dose-escalation, cohort study | 10 | AAV8 | 2e11, 6e11, 2e12 | 36.3 (22-64) | NR | 128 | 100/0 | NR |
| 101HEMB01/NCT02618915 (1/2) | DTX101 | United States, Bulgaria, United Kingdom | Open-label, dose-escalation, cohort study | 6 (3, 3) | AAVrh10 | 1.6e12, 5e12 | (50-84, 18-49) | NR | 12 | NR | Day 0 |
| NCT04135300 (1) | BBM-H901 | China | Open-label, single-arm, cohort study | 10 | AAV843 | 5e12 | NR | 100 | 13 | NR | NR |
| NCT00515710 (1/2) | AAV2-hFIX16 | United States | Open-label, dose-escalation, cohort study | 7 | AAV2 | 8e10, 4e11, 2e12 | 34 (20-63) | NR | 180 | 100/0 | NR |
NCT, National Clinical Trial; NR, not reported; vg, vector genomes.
For the dose-escalation studies, n for each dose cohort is specified in parentheses for the studies which have specified that data.
United States, Australia, Belgium, Brazil, France, Germany, Israel. Italy, Korea, South Africa, Spain, Taiwan, and United Kingdom.
United States, Australia, Canada, Israel, and Thailand.
United States, United Kingdom, Austria, France, Germany, Hungary, Italy, and Spain.
United States, Bulgaria, France, Germany, The Netherlands, and United Kingdom.
United States, Australia, Brazil, Canada, France, Germany, Greece, Japan, Korea, Saudi Arabia, Sweden, Taiwan, Turkey, and United Kingdom.
United States, Belgium, Denmark, Germany, Ireland, The Netherlands, Sweden, and United Kingdom.