Table 1.
Current and recent disease modification trials for Parkinson’s disease
| Mechanism of action | Agent | Sponsor/Partner | Phase | N | Study population | Dose | Duration | Primary outcome | Result | Ref. |
|---|---|---|---|---|---|---|---|---|---|---|
| Active α-syn immunization | PD01A (C-terminal epitope of human α-syn) | Affiris AG | I | 32 | 45–65 years, diagnosis < 4 years, stable dose of PD meds | 15 μg or 75 μg every 4 weeks × 4; 15 μg or 75 μg booster no. 1; 75 μg booster no. 2 | 52 weeks, followed by 39 weeks follow-up; 24 weeks after booster no. 1; 52 weeks after booster no. 2 | Safety and tolerability | Safe and well-tolerated, positive humoral immune response | NCT01560899, NCT01885494, NCT02216188, NCT02618941 [15] |
| Passive α-syn immunization |
PRX002/RG7935/ Prasinezumab (PASADENA) |
Roche/Prothena | II | 316 | 40–80 years, diagnosis < 2 years, PD DaTscan, no DA rx (stable MAOB-I allowed) | 1500 mg or 4500 mg vs placebo every 4 weeks × 52 weeks | 52 weeks | ΔMDS-UPDRS I–III at week 52 | Negative; positive signal in motor outcomes | NCT03100149 [16] |
| BIIB054 (SPARK) | Biogen/PSG | II | 357 | 40–80 years, diagnosis < 3 years, PD DaTscan, no PD meds | 250 mg, 1250 mg, 3500 mg vs placebo every 4 weeks × 52 weeks | 52 weeks with follow-up to 72 weeks and 178 weeks | ΔMDS-UPDRS I–III at weeks 52 and 72 | Active, not recruiting; estimated completion 6/2021 | NCT03318523 | |
| Lu AF82422 | Lundbeck | I | 84 | 40–80 years, stable dose × 3 months | Single ascending dose | 12 weeks | Safety and tolerability | Recruiting; estimated completion 12/2020 | NCT03611569 | |
| MEDI-1341 | AstraZeneca | I | 48 | Healthy volunteers | Single ascending dose | 13 weeks | Safety and tolerability | Estimated completion 1/2021 | NCT03272165 | |
| Calcium channel blocker | Isradipine (STEADY-PD III) | NINDS/PSG/MJFF | III | 336 | > 30 years, diagnosis < 3 years, no DA rx | 5 mg twice daily vs placebo | 36 months | ΔUPDRS I–III at month 36 | Negative, no benefit on secondary outcomes | NCT02168842 [17] |
| Urate elevation/antioxidant | Inosine (SURE-PD3) | NINDS/PSG/MJFF | III | 298 | > 30 years, diagnosis < 3 years, PD DaTscan, no DA rx (stable MAOB-I allowed), serum urate < 5.7 mg/dL | Up to 3 g/day, titrated to serum urate level 7.1–8.0 mg/dL | 24 months | ΔMDS-UPDRS I–III at month 24 | Negative, early termination | NCT02642393 [18] |
| Statin/anti-inflammation | Simvastatin (PD STAT) | University Hospital Plymouth NHS Trust | II | 235 | 40–90 years, H&Y < 3, on DA rx with wearing off | 40 mg daily for 1 month, then 80 mg | 24 months with 2 month washout | ΔMDS-UPDRS III (OFF state) at month 24 | Negative | NCT02787590 [19] |
| Iron chelation | Deferiprone (SKY) | ApoPharma | II | 140 | 18–80 years, diagnosis < 3 years, stable dose of DA rx | 300, 600, 900, or 1200 mg twice daily vs placebo | 9 months | ΔMDS-UPDRS I–III at month 9 | Study completed 9/2019, results pending | NCT02728843 |
| Deferiprone (FAIRPARKII) | ApoPharma | II | 372 | < 80 years, disease duration < 18 months, no DA rx | 15 mg/kg twice daily vs placebo | 36 weeks | ΔMDS-UPDRS I–III at week 36 | Active, not recruiting; estimated completion 4/2021 | NCT02655315 | |
| Glucagon-like peptide 1 agonist | Exenatide | University College, London | II | 60 | 25–75 years, on DA rx with wearing off phenomena | 2 mg sc once weekly vs placebo | 48 weeks | ΔMDS-UPDRS III (OFF state) at week 60 | Positive; ΔMDS-UPDRS III + 1.0 (exenatide) vs − 2.1 (placebo) (p = 0.0318) | NCT01971242 [20] |
| Exenatide (Exenatide-PD3) | University College, London | III | 200 | 25–80 years, on DA rx for > 4 weeks | 2 mg sc weekly vs placebo | 96 weeks | ΔMDS-UPDRS I–III (OFF state) at week 96 | Recruiting; estimated completion 9/2023 | NCT04232969 | |
| Exenatide | Center for Neurology, Stockholm | II | 60 | 25–80 years, H&Y < 2 (ON), on levodopa | 2 mg sc weekly vs placebo | 18 months | FDG-PET network analysis | Recruiting, estimated completion 10/2022 | NCT04305002 | |
| SR-Exenatide (PT320) (sustained release) | Peptron, Inc. | II | 99 | 40–75 years, diagnosis < 24 months, stable dose of levodopa | 2 mg sc weekly vs 2.5 mg sc every 2 weeks vs placebo | 48 weeks | ΔMDS-UPDRS III at week 48 | Recruiting, estimated completion 12/2021 | NCT04269642 | |
| NLY01 (pegylated exenatide) | Neuraly, Inc. | II | 240 | 30–80 years, PD DaTscan, no DA rx | 2.5 mg vs 5 mg sc weekly vs placebo | 36 weeks | ΔMDS-UPDRS II–III at week 36 | Recruiting, estimated completion 4/2021 | NCT04154072 | |
| Lixisenatide (LixiPark) | University Hospital, Toulouse | II | 156 | 40–75 years, diagnosis < 3 years, stable DA rx | 10 μg/day × 14 days, then 20 μg/day vs placebo | 12 months | ΔMDS-UPDRS III at month 12 | Active, not recruiting; estimated completion 12/2021 | NCT03439943 | |
| Liraglutide | Cedars-Sinai Medical Center | II | 57 | 25–85 years, diagnosis > 2 years, DA-responsive | 1.8 mg sc daily vs placebo | 54 weeks | ΔMDS-UPDRS III at weeks 28 and 54 | Recruiting, estimated completion 12/2021 | NCT02953665 | |
| c-Abl tyrosine kinase inhibitor | Nilotinib (NILO-PD) | Northwestern University/PSG/MJFF | II | 76 | 40–79 years, diagnosis > 5 years, stable DA rx | 150 mg or 300 mg once daily vs placebo | 6 months | Safety and tolerability | Safe and well-tolerated; low CSF exposure with no change in dopamine metabolites | NCT03205488 [21] |
| Nilotinib (PD Nilotinib) | Georgetown University | II | 75 | 40–90 years, H&Y 2.5–3, stable DA rx | 150 mg or 300 mg once daily vs placebo | 12 months | Safety and tolerability | Reasonably safe, increased CSF levels of DA metabolites | NCT02954978 [22] | |
| K0706 (PROSEEK) | Sun Pharma | II | 504 | > 50 years, symptoms < 3 years, PD DaTscan, no DA rx | Low dose vs high dose once daily vs placebo | 40 weeks | ΔMDS-UPDRS II–III at week 40 | Recruiting, estimated completion 3/2023 | NCT03655236 | |
| GBA | Ambroxol | University College, London | II | 23 | 40–80 years, H&Y 1–3, 1:1 with and without GBA1 mutations | Escalating dose to 1260 mg daily | 186 days | GCase, ambroxol levels in blood, CSF | Positive; decrease in GCase activity by 19% (p = 0.04), increased CSF ambroxol | NCT02941822 [23] |
| Ambroxol | Lawson Health Research Institute | II | 75 | > 50 years, mild to moderate dementia, H&Y 2–3.5 | 1050 mg daily vs placebo | 52 weeks | ΔADAS-cog, ADCS-CGIC at weeks 26 and 52 | Recruiting, estimated completion 12/2021 | NCT02914366 | |
| GZ/SAR402671 (MOVES-PD) | Sanofi/Genzyme | II | 270 | 18–80 years, H&Y < 2, PD-associated GBA1 mutation, stable DA rx | Part 1: increasing dose once daily; part 2: determined in part 1 | Part 1: up to 48–66 weeks; part 2: 52-week rx, followed by 104 weeks | Part 1: safety and tolerability; part 2: ΔMDS-UPDRS II–III at week 8 and 52 | Active, not recruiting; estimated completion 2/2024 | NCT02906020 |
GBA, GCase, glucocerebrosidase; NINDS, National Institute of Neurological Disorders and Stroke; PSG, Parkinson Study Group; MJFF, Michael J. Fox Foundation; DA rx, dopaminergic treatment; MAOB-I, monoamine oxidase B inhibitor; H&Y, Hoehn and Yahr stage); sc, subcutaneous; MDS-UPDRS, Movement Disorder Society-Unified Parkinson Disease Rating Scale; FDG-PET, fluorodeoxyglucose positron emission tomography N; ADAS-cog, Alzheimer’s Disease Assessment Scale-Cognitive Subscale; ADCS-CGIC, Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change; NCT, National Clinical Trial number assigned on clinicaltrials.gov. Estimated completion is defined as “the date the final subject was examined or received an intervention for purposes of final collection of data for the primary and secondary outcomes measures and adverse events (e.g., last subject’s last visit), whether the clinical trial concluded according to the pre-specified protocol or was terminated” (clinicaltrials.gov). Clinical trials targeting glucocerebrosidase are included in this table for completeness; they are not included in this review and are discussed elsewhere in this volume [14]. The table is not exhaustive and is not intended to include all recent/current phase 1 and 2 trials nor any non-pharmacological trials