Table 3.
Gene therapy trials for HD, SMA and ALS
| Gene therapy | Delivery route | Identifier | Phase | Patients | Primary endpoint | Duration | Ref | ||
|---|---|---|---|---|---|---|---|---|---|
| Huntington’s disease | Total HTT |
ASO-HTT | IT | NCT02519036 | 1/2 | Early manifest HD, age 25-65 | Safety and tolerability | 2015-2017 | 124,136,154 |
| ASO-HTT | IT | NCT03342053 | 2 | From NCT02519036 | Safety and tolerability | 2017-2019 | |||
| ASO-HTT | IT | NCT04000594 | 1 | Manifest HD, age 25-65 | Pharmacokinetics and pharmacodynamics | 2019-2021 | |||
| ASO-HTT | IT | NCT03761849 | 3 | Manifest HD, age 25-65 | Disease progression and total functional capacity | 2019-2022 | 124 | ||
| ASO-HTT | IT | NCT03842969 | 3 | Patients who participated in prior RG6042 (ASO-HTT) studies | Long-term safety and tolerability, suicide risk, cognition | 2019-2024 | |||
| AAV5-miHTT | IP (striatum) | NCT04120493 | 1/2 | Early manifest HD, ≤ 40 CAG repeats in HTT | Safety | 2019-2026 | |||
| Mutated HTT | ASO-mHTT | IT | NCT03225833 | 1/2 | Early manifest HD, carrying a targeted SNP rs362307, age 25-65 | Safety and tolerability | 2017-2020 | 136 | |
| ASO-mHTT | IT | NCT03225846 | 1/2 | Early manifest HD, carrying a targeted SNP rs362331, age 25-65 | Safety and tolerability | 2017-2020 | 136 | ||
| SMA | SMN1 | AAV9-SMN | IV | NCT02122952 | 1 | Type 1 SMA, ≤ 6 or 9 months of age | Safety | 2014-2019 | 2,55 |
| AAV9-SMN | IV | NCT03306277 | 3 | Type 1 SMA, ≤ 6 months of age | Independent sitting, survival | 2017-2019 | |||
| AAV9-SMN | IV | NCT03381729 | 1 | Type 2 SMA (onset at < 12 months of age), age 6 to 60 months | Safety and tolerability | 2017-2021 | |||
| AAV9-SMN | IV | NCT03461289 | 3 | Type 1 SMA, ≤ 6 months of age | Sitting without support | 2018-2020 | |||
| AAV9-SMN | IV | NCT03505099 | 3 | Pre-symptomatic SMA with 2 or 3 copies of SMN2, ≤ 6 weeks of age | Independent sitting, standing without support | 2018-2021 | |||
| AAV9-SMN | IV | NCT03837184 | 3 | Type 1 SMA, ≤ 6 months of age | Sitting without support | 2019-2033 | |||
| SMN2 | ASO-SMN2 | IT | NCT01494701 | 1 | Age 2-14 | Safety, tolerability, and pharmacokinetics | 2011-2013 | 155 | |
| ASO-SMN2 | IT | NCT01703988 | 1/2 | Age 2-15 | Safety and tolerability | 2012-2015 | 155 | ||
| ASO-SMN2 | IT | NCT01780246 | 1 | From NCT01494701 | Safety and tolerability | 2013-2014 | 155 | ||
| ASO-SMN2 | IT | NCT01839656 | 2 | Age ≤ 210 days, disease onset between 21 and 180 days of age | Motor milestones | 2013-2017 | 52,155 | ||
| ASO-SMN2 | IT | NCT02052791 | 1 | From NCT01703988or NCT01780246 | Safety and tolerability | 2014-2017 | 155 | ||
| ASO-SMN2 | IT | NCT02292537 | 3 | Disease onset at > 6 months of age, age 2-12 | Motor function | 2014-2017 | 155,156 | ||
| ASO-SMN2 | IT | NCT02386553 | 2 | SMA with 2 or 3 copies of SMN2, ≤ 6 weeks of age | Respiratory intervention, survival | 2015-2025 | 52 | ||
| ASO-SMN2 | IT | NCT02594124 | 3 | From NCT02193074, NCT02292537, NCT02052791, NCT01839656 | Long-term safety and tolerability | 2015-2023 | |||
| ASO-SMN2 | IT | NCT04050852 | 1 | Age 5-21 | Pulmonary function | 2019-2020 | |||
| ASO-SMN2 | IT | NCT04089566 | 2/3 | Child, adult, older adult | Safety and tolerability with high doses, neuromuscular function | 2020-2022 | |||
| ALS | SOD1 | ASO-SOD1 | IT | NCT01041222 | 1 | Familial ALS with SOD1 mutation, ≥18 years of age | Safety, tolerability, and pharmacokinetics | 2010-2012 | 141 |
| ASO-SOD1 | IT | NCT02623699 | 1/2 | Familial ALS with SOD1 mutation, ≥18 years of age | Safety, tolerability, Pharmacokinetics and progression of disability | 2016-2021 | 142 | ||
| ASO-SOD1 | IT | NCT03070119 | 3 | From NCT02623699 | Long-term safety and tolerability | 2017-2023 | |||
| ASO-SOD1 | IT | NCT03764488 | 1 | Age 18-65 | Drug distribution in CNS | 2018-2020 | |||
| C9orf72 | ASO-C9orf72 | IT | NCT03626012 | 1 | ALS with C9orf72 mutation, ≥18 years of age | Safety and tolerability | 2018-2021 | ||
| ASO-C9orf72 | IT | NCT04288856 | 1 | From NCT03626012 | Long-term safety and tolerability | 2020-2023 | |||
Intraparenchymal (IP)
Intracisternal (IC)
Intravenous (IV)
Intrathecal (IT)