Trial of Prasinezumab in Early-Stage Parkinson's Disease

被引：239

作者：

Pagano, G. ^{[1
,8
]}

Taylor, K. I. ^{[1
]}

Anzures-Cabrera, J. ^{[9
]}

Marchesi, M. ^{[7
]}

Simuni, T. ^{[11
]}

Marek, K. ^{[12
]}

Postuma, R. B. ^{[13
,14
]}

Pavese, N. ^{[10
]}

Stocchi, F. ^{[15
,16
]}

Azulay, J. -P. ^{[17
]}

Mollenhauer, B. ^{[18
,19
]}

Lopez-Manzanares, L. ^{[25
]}

Russell, D. S. ^{[12
]}

Boyd, J. T. ^{[28
]}

Nicholas, A. P. ^{[29
]}

Luquin, M. R. ^{[26
]}

Hauser, R. A. ^{[27
]}

Gasser, T. ^{[20
,21
]}

Poewe, W. ^{[30
]}

Ricci, B. ^{[2
]}

Boulay, A. ^{[1
]}

Vogt, A. ^{[1
]}

Boess, F. G. ^{[1
]}

Dukart, J. ^{[1
,22
,23
]}

D'Urso, G. ^{[1
]}

Finch, R. ^{[9
]}

Zanigni, S. ^{[5
,6
]}

Monnet, A. ^{[5
,6
]}

Pross, N. ^{[5
,6
]}

Hahn, A. ^{[24
]}

Svoboda, H. ^{[1
]}

Britschgi, M. ^{[1
]}

Lipsmeier, F. ^{[3
,4
]}

Volkova-Volkmar, E. ^{[3
,4
]}

Lindemann, M. ^{[3
,4
]}

Dziadek, S. ^{[1
]}

Holiga, S. ^{[1
]}

Rukina, D. ^{[7
]}

Kustermann, T. ^{[1
]}

Kerchner, G. A. ^{[1
]}

Fontoura, P. ^{[5
,6
]}

Umbricht, D. ^{[1
]}

Doody, R. ^{[5
,6
]}

Nikolcheva, T. ^{[5
,6
]}

Bonni, A. ^{[1
]}

机构：

[1] F Hoffmann La Roche, Neurosci & Rare Dis, Discovery & Translat Area, Basel, Switzerland

[2] F Hoffmann La Roche, Pharmaceut Sci, Basel, Switzerland

[3] F Hoffmann La Roche, Roche Pharma Res & Early Dev pRED, Basel, Switzerland

[4] F Hoffmann La Roche, Roche pRED Informat, Basel, Switzerland

[5] F Hoffmann La Roche, Roche Innovat Ctr Basel, Basel, Switzerland

[6] F Hoffmann La Roche, Prod Dev Neurosci, Basel, Switzerland

[7] F Hoffmann La Roche, Prod Dev Safety, Basel, Switzerland

[8] Univ Exeter, Med Sch, London, England

[9] Roche Prod, Welwyn Garden City, Herts, England

[10] Newcastle Univ, Clin Ageing Res Unit, Newcastle Upon Tyne, Tyne & Wear, England

[11] Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL 60611 USA

[12] Inst Neurodegenerat Disorders, New Haven, CT USA

[13] McGill Univ, Dept Neurol, Montreal, PQ, Canada

[14] Montreal Neurol Inst, Montreal, PQ, Canada

[15] Univ San Raffaele Roma, Rome, Italy

[16] IRCCS San Raffaele Pisana, Inst Res & Med Care, Rome, Italy

[17] Ctr Hosp Timone, Marseille, France

[18] Paracelsus Elena Klin, Kassel, Germany

[19] Univ Med Ctr Gottingen, Dept Neurol, Gottingen, Germany

[20] Univ Tubingen, Hertie Inst Clin Brain Res, Tubingen, Germany

[21] German Ctr Neurodegenerat Dis, Tubingen, Germany

[22] Res Ctr Julich, Inst Neurosci & Med, Brain & Behav, Julich, Germany

[23] Heinrich Heine Univ Dusseldorf, Med Fac, Inst Syst Neurosci, Dusseldorf, Germany

[24] Excelya Germany, Freiburg, Germany

[25] Univ Hosp La Princesa, Madrid, Spain

[26] Univ Clin Navarra, Pamplona, Spain

[27] Univ S Florida, Tampa, FL USA

[28] Univ Vermont, Larner Coll Med, Burlington, VT USA

[29] Univ Alabama Birmingham, Med Ctr, Birmingham, AL 35294 USA

[30] Innsbruck Med Univ, Dept Neurol, Innsbruck, Austria

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2022年 / 387卷 / 05期

关键词：

ALPHA-SYNUCLEIN; PROPAGATION;

D O I：

10.1056/NEJMoa2202867

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND Aggregated alpha-synuclein plays an important role in the pathogenesis of Parkinson's disease. The monoclonal antibody prasinezumab, directed at aggregated alpha-synuclein, is being studied for its effect on Parkinson's disease. METHODS In this phase 2 trial, we randomly assigned participants with early-stage Parkinson's disease in a 1:1:1 ratio to receive intravenous placebo or prasinezumab at a dose of 1500 mg or 4500 mg every 4 weeks for 52 weeks. The primary end point was the change from baseline to week 52 in the sum of scores on parts I, II, and III of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 236, with higher scores indicating greater impairment). Secondary end points included the dopamine transporter levels in the putamen of the hemisphere ipsilateral to the clinically more affected side of the body, as measured by I-123-ioflupane single-photon-emission computed tomography (SPECT). RESULTS A total of 316 participants were enrolled; 105 were assigned to receive placebo, 105 to receive 1500 mg of prasinezumab, and 106 to receive 4500 mg of prasinezumab. The baseline mean MDS-UPDRS scores were 32.0 in the placebo group, 31.5 in the 1500-mg group, and 30.8 in the 4500-mg group, and mean (+/- SE) changes from baseline to 52 weeks were 9.4 +/- 1.2 in the placebo group, 7.4 +/- 1.2 in the 1500-mg group (difference vs. placebo, -2.0; 80% confidence interval [CI], -4.2 to 0.2; P = 0.24), and 8.8 +/- 1.2 in the 4500-mg group (difference vs. placebo, -0.6; 80% CI, -2.8 to 1.6; P = 0.72). There was no substantial difference between the active-treatment groups and the placebo group in dopamine transporter levels on SPECT. The results for most clinical secondary end points were similar in the active-treatment groups and the placebo group. Serious adverse events occurred in 6.7% of the participants in the 1500-mg group and in 7.5% of those in the 4500-mg group; infusion reactions occurred in 19.0% and 34.0%, respectively. CONCLUSIONS Prasinezumab therapy had no meaningful effect on global or imaging measures of Parkinson's disease progression as compared with placebo and was associated with infusion reactions.

引用

页码：421 / 432

页数：12

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