Trial of Cinpanemab in early Parkinson’s disease

Summary

Background

Aggregated α-synuclein plays an important role in the pathogenesis of Parkinson’s disease. Cinpanemab, a human-derived monoclonal antibody that binds to α-synuclein, is being evaluated as a modifying treatment for Parkinson’s disease.

Methods

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In a 52-week, double-blind, multicenter, phase 2 trial, we randomly assigned, in a 2:1:2:2 ratio, participants with early-stage Parkinson’s disease to receive intravenous infusions of placebo (control) or cinpanemab at a dose of 250 mg, 1250 mg, or 3500 mg every 4 weeks, followed by a blind extension period of the active treatment dose up to 112 weeks . The primary endpoints were changes from baseline in the Movement Disorder Society-sponsored review of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) total score (range 0 to 236, higher scores indicating poorer performance) at weeks 52 and 72 Secondary endpoints included MDS-UPDRS subscale scores and striatal binding assessed on dopamine transporter single-photon emission computed tomography (DaT -SPECT).

Results

Of the 357 participants enrolled, 100 were assigned to the control group, 55 to the cinpanemab 250 mg group, 102 to the 1250 mg group and 100 to the 3500 mg group. The trial was stopped after the week 72 interim analysis due to lack of efficacy. The change at week 52 in the MDS-UPDRS score was 10.8 points in the control group, 10.5 points in the 250 mg group, 11.3 points in the 1250 mg group and 10.9 points in the the 3500 mg group (adjusted mean difference vs control, −0.3 points [95% confidence interval {CI}, −4.9 to 4.3], P=0.90; 0.5 points [95% CI, −3.3 to 4.3], P=0.80; and 0.1 points [95% CI, −3.8 to 4.0], P = 0.97, respectively). The adjusted mean difference at 72 weeks between participants who received cinpanemab for 72 weeks and the pooled group of those who started cinpanemab at 52 weeks was −0.9 points (95% CI, −5.6 to 3.8) for the 250 mg dose, 0.6 points (95% CI, -3.3 to 4.4) for the 1250 mg dose and -0.8 points (95% CI, – 4.6 to 3.0) for the 3500 mg dose. The results for the secondary endpoints were similar to those for the primary endpoints. DaT-SPECT imaging at week 52 showed no difference between the control group and any cinpanemab group. The most common adverse events with cinpanemab were headache, nasopharyngitis and falls.

conclusion

In participants with early-stage Parkinson’s disease, the effects of cinpanemab on clinical measures of disease progression and changes in DaT-SPECT imaging did not differ from those of placebo over a 52-week period . (Funded by Biogen; SPARK ClinicalTrials.gov number, NCT03318523.)

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Cinpanemab in early Parkinson’s disease
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Elna M. Lemons