PASADENA
(2022)Objective
To evaluate the efficacy and safety of prasinezumab, a monoclonal antibody targeting aggregated α-synuclein, on disease progression in early-stage Parkinson's disease.
Study Summary
• MDS-UPDRS change at 52 weeks: placebo +9.4, 1500 mg +7.4 (P=0.24), 4500 mg +8.8 (P=0.72)
• No effect on dopamine transporter SPECT imaging; infusion reactions occurred in 19-34% of prasinezumab patients
Intervention
Prasinezumab 1500 mg or 4500 mg IV every 4 weeks for 52 weeks vs placebo
Inclusion Criteria
Adults with early-stage PD (Hoehn & Yahr 1-2), DaTscan consistent with PD, treatment-naive (MAO-B inhibitors allowed if stable)
Study Design
Arms: Placebo, Prasinezumab 1500 mg, Prasinezumab 4500 mg
Patients per Arm: Placebo: 105, 1500 mg: 105, 4500 mg: 106
Outcome
• No difference in DaTscan striatal binding ratio
• Infusion reactions: 16% (placebo) vs 19% (1500 mg) vs 34% (4500 mg)
Bottom Line
In this phase 2 trial, prasinezumab therapy showed no meaningful effect on global or imaging measures of Parkinson's disease progression compared with placebo over 52 weeks in patients with early-stage Parkinson's disease, though it was associated with infusion reactions.
Major Points
- Randomized, double-blind, placebo-controlled phase 2 trial of prasinezumab in early-stage Parkinson's disease
- 316 participants randomized 1:1:1 to placebo, prasinezumab 1500 mg, or prasinezumab 4500 mg IV every 4 weeks for 52 weeks
- Primary endpoint: change in MDS-UPDRS parts I, II, and III total score from baseline to week 52
- No significant difference in primary endpoint between prasinezumab groups and placebo (1500 mg: -2.0 points, P=0.24; 4500 mg: -0.6 points, P=0.72)
- Infusion reactions were the most frequently reported adverse event, occurring in 19.0% (1500 mg) and 34.0% (4500 mg) vs 16.2% (placebo)
- Exploratory delayed-start analysis in Part 2 extension (up to 104 weeks) also showed no benefit of prasinezumab
Study Design
- Study Type
- Phase 2 randomized controlled trial
- Randomization
- Yes
- Blinding
- Double-blind
- Sample Size
- 316
- Follow-up
- 52 weeks (Part 1), with optional extension to 104 weeks (Part 2)
- Centers
- 57
- Countries
- Austria, France, Germany, Spain, United States
Primary Outcome
Definition: Change from baseline to week 52 in MDS-UPDRS parts I, II, and III total score (range 0-236, higher = worse)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 9.4±1.2 | 7.4±1.2 (1500 mg); 8.8±1.2 (4500 mg) | - (Not reported (80% CI provided)) | P=0.24 (1500 mg); P=0.72 (4500 mg) |
Limitations & Criticisms
- Approximately 30% of participants started medication for symptoms during the trial, leading to data censoring
- Trial population may not be representative due to underrepresentation of non-White populations
- No testing for target engagement
- Limited duration of follow-up (52 weeks)
- Infusion reactions were more common in treatment groups, potentially affecting blinding
Citation
N Engl J Med 2022;387:421-432