Table 2.
Summary of dopamine synthetic GT trials to date
| NCT number, sponsor, and site | Virus and dosing | Study details and outcomes |
|---|---|---|
|
Sponsor: Genzyme Site: University of California Duration: 6 months Status: completed Refs: [61] |
AAV2-AADC Putamen, bilateral Low dose: 9 × 1010 vg/patient High dose: 3 × 1011 vg/patient Infusion: 2 deposits of 50 μl per putamen iMRI—no |
Category: phase 1, safety and tolerability Patients: total 10 subjects, 5 per dose Disease stage: advanced PD; avg. duration 13/9.4 years Primary: safety. Well tolerated. One patient with symptomatic hemorrhage, almost complete recovery. Two with asymptomatic hemorrhages Secondary: improvements in UPDRS, Hauser diaries, and FMT-PET |
|
NCT: no number Sponsor: Genzyme Site: Jichi University Duration: 6 months Status: completed Refs: [62] |
AAV2-AADC Putamen, bilateral Dose: 3 × 1011 vg/patient Infusion: 2 deposits of 50 μl/putamen iMRI—no |
Category: phase 1, safety and tolerability: Patients: 6 patients Disease stage: advanced PD; avg. duration 10 years Primary: safety. Well tolerated. One patient with small hemorrhage and transient symptoms. Secondary: improvements in UPDRS and 18F-m-tyrosine PET |
|
Sponsor: Voyager Therapeutics Site: Univ. of California and Univ. of Pittsburgh Duration: 12 months Status: completed Refs: [63] |
AAV2-AADC (VY-AADC01) Putamen, bilateral Low dose: 7.5 × 1011 vg/patient Medium dose: 1.5 × 1012 vg/patient High dose: 4.7 × 1012 vg/patient Infusion: iMRI/SmartFlow, 2 or 3 tracts, 450–900 μl/putamen iMRI—yes |
Category: phase 1, safety /dose finding Patients: 15 subjects, 5 per dose Disease stage: advanced PD Primary: safety. Well tolerated. One patient with three SAEs, due to immobility during procedure—DVT, PE, AF. Secondary: improvements in all—putaminal coverage (iMRI); 18F-DOPA PET at 6 months; OFF UPDRS3 at 12 months; PDQ-39; levodopa dose |
|
NCT03562494 (RESTORE-1) Sponsor: Voyager Therapeutics Site: multicenter Study duration: Status: closing 2020 Refs: not yet published |
AAV2-AADC (VY-AADC02) Putamen, bilateral Up to 2.5 × 1012 vg/patient Infusion: 2 or 3 tracts, up to 900 μl/putamen iMRI—yes |
Category: phase 2, blinded RCT, sham surgery control Patients: 42 subjects Disease stage: advanced PD Primary: safety (multiple, including psychiatric); striatal coverage; diary; PET (18F-DOPA PET) Secondary: pending |
|
Sponsor: Oxford Biomedica Site: Paris (France) and Cambridge (UK) Duration: 12 months Status: completed |
EIAV-triple enzyme (ProSavin®) Putamen, bilateral Dose: three dose levels, 1·9 × 107, 4.0 × 107 and 1.0 × 108 transducing units (TU)/patient iMRI—no |
Category: phase 1, safety and dose finding Patients: 15 subjects, 3 dose levels. Disease stage: advanced PD; avg. duration 13.9 years [8–27] Primary: safety. Well tolerated; no SAEs due to treatment Secondary: improvements in UPDRS 3 and PDQ-39; modest improvements in raclopride-PET, and LED |
|
NCT03720418 (SUNRISE-PD) Sponsor: Axovant Site: Paris (France), Cambridge (UK), and National Hosp. (London) Duration: ongoing Status: active Refs: not yet published |
EIAV-triple enzyme (OXB-102) Putamen, bilateral Dose: three dose levels, 4.2 × 106, 1.4 × 107, and 4.2 × 107 TU/patient Infusion: 3 deposits of 100 μl/putamen iMRI—no |
Category: phase 1/2—safety and dose finding, moving to sham surgery Disease stage: advanced PD Patients: 3–4 patients per dose, 3 dose levels Primary: safety Secondary: UPDRS, Hauser diaries, PET, dyskinesia rating scale; Hauser diaries; PDQ-39, SF-36, and clinical global impression |