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PADOVA

PrAsinezumab in early-stage Parkinson's Disease in levodopa (L-DOPA)- or MAO-Bi-treated patients - efficacy and safety eVAluation

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Year of Publication: 2025

Authors: Tania Nikolcheva, Gennaro Pagano, Nathalie Pross, ..., Ronald B. Postuma

Journal: Parkinsonism and Related Disorders

Citation: Parkinsonism Relat Disord 2025;132:107257

Link: https://doi.org/10.1016/j.parkreldis.2024.107257

Clinical Question

Does prasinezumab delay motor progression in early-stage Parkinson's disease patients receiving standard-of-care symptomatic medications (levodopa or MAO-B inhibitors)?

Bottom Line

PADOVA is a Phase 2b trial designed to confirm the efficacy signal observed in PASADENA by testing prasinezumab in a broader, more representative early-stage PD population on stable symptomatic therapy. The study successfully enrolled 586 participants and reached primary completion in September 2024. Results pending.

Major Points

  • Phase 2b, multicenter, randomized, double-blind, placebo-controlled trial across 112 sites in 9 countries
  • 586 participants with early-stage PD enrolled between May 2021 and March 2023
  • Participants on stable symptomatic monotherapy: 74.2% on levodopa (up to 450 mg/day), 25.8% on MAO-B inhibitors
  • Randomized 1:1 to prasinezumab 1500 mg IV Q4W vs placebo, stratified by background medication
  • Primary endpoint: time to confirmed motor progression (≥5 point increase in MDS-UPDRS Part III in OFF-state)
  • 91.7% of participants with CSF had positive alpha-synuclein seed amplification assay
  • Primary completion date reached September 11, 2024; results pending

Design

Study Type: Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group

Randomization: 1

Blinding: Double-blind

Enrollment Period: May 5, 2021 to March 22, 2023

Follow-up Duration: ≥76 weeks double-blind + 104 weeks open-label extension

Centers: 112

Countries: Austria, Canada, France, Italy, Luxembourg, Poland, Spain, United Kingdom, United States

Sample Size: 586

Analysis: Time-to-event analysis using stratified log-rank test; 248 events provides 80% power to detect HR 0.7

Inclusion Criteria

  • Diagnosis of idiopathic PD (MDS criteria) with bradykinesia plus resting tremor or rigidity
  • Age 50-85 years
  • Time from diagnosis 3 months to 3 years
  • Hoehn and Yahr Stage 1 or 2
  • DaT-SPECT consistent with dopamine transporter deficit
  • Stable L-DOPA dose (up to 450 mg/day) OR MAO-B inhibitor monotherapy for ≥3 months
  • No motor complications in L-DOPA subgroup

Exclusion Criteria

  • Parkinsonian syndrome other than PD
  • PD dementia or significant neurological disease other than PD
  • Treatment with dopamine agonists at baseline

Arms

FieldControlPrasinezumab
InterventionPlacebo IV infusion every 4 weeksPrasinezumab 1500 mg IV Q4W with premedication for first 3 infusions
Duration≥76 weeks≥76 weeks + optional 104-week OLE

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-value
Time to confirmed motor progression (≥5 points MDS-UPDRS Part III in OFF-state, sustained over 2 consecutive visits)PrimaryResults pendingResults pendingResults pending
Change from baseline to Week 76 in MDS-UPDRS Part III (OFF-state)SecondaryResults pendingResults pendingResults pending
Time to meaningful worsening on CGI-CSecondaryResults pendingResults pendingResults pending
Time to onset of motor complications (MDS-UPDRS Part IV)SecondaryResults pendingResults pendingResults pending

Subgroup Analysis

Subgroup analyses planned by progression rate, baseline characteristics, MAO-Bi vs L-DOPA cohorts

Criticisms

  • Protocol/baseline paper; efficacy and safety results pending
  • 787 screened, 201 (25.5%) did not qualify
  • PADOVA population more advanced than PASADENA (older, longer disease duration, higher MDS-UPDRS Part III)
  • Potential masking effect of symptomatic medication changes on motor outcomes
  • Only 71 participants (12%) consented to lumbar puncture for CSF biomarker analysis

Funding

F. Hoffmann-La Roche Ltd

Based on: PADOVA (Parkinsonism and Related Disorders, 2025)

Authors: Tania Nikolcheva, Gennaro Pagano, Nathalie Pross, ..., Ronald B. Postuma

Citation: Parkinsonism Relat Disord 2025;132:107257

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