SPARK
(2022)Objective
Cinpanemab – To evaluate whether targeting aggregated α-synuclein with cinpanemab can slow clinical progression in early Parkinson's disease.
Study Summary
• No clinical, functional, or imaging benefit observed.
• Trial was terminated early for futility after 72-week analysis.
Intervention
Phase 2, multicenter, randomized, double-blind, placebo-controlled trial with delayed-start design. Patients with early Parkinson's disease were assigned to receive intravenous cinpanemab (250 mg, 1250 mg, or 3500 mg) or placebo every 4 weeks for 52 weeks, followed by a blinded extension phase to 112 weeks. Primary outcomes were changes in MDS-UPDRS total scores at weeks 52 and 72.
Inclusion Criteria
Ages 40–80 with early-stage Parkinson's disease (diagnosed <3 years), Hoehn and Yahr ≤2.5, no dopaminergic treatment in prior 12 weeks, and striatal dopaminergic deficit confirmed by DaT-SPECT. Excluded if MoCA <23 or with clinical dementia, freezing of gait, or prior α-synuclein immunotherapy.
Study Design
Arms: Cinpanemab (3 dose levels) vs. Placebo
Patients per Arm: Placebo: 100; Cinpanemab 250 mg: 55; 1250 mg: 102; 3500 mg: 100
Outcome
• At 72 weeks: No difference between early- and delayed-start groups (all dose groups P>0.6)
• DaT-SPECT striatal binding: No difference at 52 or 96 weeks
• Most common AEs: Headache, nasopharyngitis, falls
• Serious AEs: 5% in cinpanemab groups; 1 death (MI, unrelated)