Trial of Prasinezumab in Early-Stage Parkinson's Disease.

Antibodies, Monoclonal, Humanized / therapeutic use Antiparkinson Agents / therapeutic use Dopamine Plasma Membrane Transport Proteins / therapeutic use Double-Blind Method Humans Parkinson Disease / drug therapy Treatment Outcome alpha-Synuclein / antagonists & inhibitors

Journal

The New England journal of medicine

ISSN: 1533-4406

Titre abrégé: N Engl J Med

Pays: United States

ID NLM: 0255562

Informations de publication

Date de publication:
04 08 2022

Historique:

entrez: 3 8 2022

pubmed: 4 8 2022

medline: 6 8 2022

Statut: ppublish

Résumé

Aggregated α-synuclein plays an important role in the pathogenesis of Parkinson's disease. The monoclonal antibody prasinezumab, directed at aggregated α-synuclein, is being studied for its effect on Parkinson's disease. 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 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. 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. (Funded by F. Hoffmann-La Roche and Prothena Biosciences; PASADENA ClinicalTrials.gov number, NCT03100149.).

Sections du résumé

BACKGROUND

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

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. (Funded by F. Hoffmann-La Roche and Prothena Biosciences; PASADENA ClinicalTrials.gov number, NCT03100149.).

Identifiants

DOI: 10.1056/NEJMoa2202867 PMID: 35921451

pubmed: 35921451

doi: 10.1056/NEJMoa2202867

doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0

Antiparkinson Agents 0

Dopamine Plasma Membrane Transport Proteins 0

alpha-Synuclein 0

Banques de données

ClinicalTrials.gov

['NCT03100149']

Types de publication

Clinical Trial, Phase II Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

421-432

Investigateurs

Claudia Altendorf (C)

Chareyna Anandan (C)

Giulia Andrews (G)

Solène Ansquer (S)

Raphaele Arrouasse (R)

Sana Aslam (S)

Jean-Philippe Azulay (JP)

Jeanette Baker (J)

Ernest Balaguer Martinez (EB)

Shadi Barbu (S)

Kara Bardram (K)

Danny Bega (D)

Helena Bejr-Kasem Marco (H)

Isabelle Benatru (I)

Eve Benchetrit (E)

Felix Bernhard (F)

Amit Besharat (A)

Sagari Bette (S)

Amelie Bichon (A)

Andrew Billnitzer (A)

Sophie Blondeau (S)

Thomas Boraud (T)

Freiderike Borngräber (F)

James Boyd (J)

Kathrin Brockmann (K)

Matthew Brodsky (M)

Ethan Brown (E)

Christof Bruecke (C)

Fabienne Calvas (F)

Monica Canelo (M)

Federico Carbone (F)

Claire Carroll (C)

Laura Casado Fernandez (L)

Catherine Casse-Parrot (C)

Anna Castrioto (A)

Helene Catala (H)

Justine Chan (J)

Samia Cheriet (S)

Anthony Ciabarra (A)

Joseph Classen (J)

Juliana Coleman (J)

Robert Coleman (R)

Yaroslau Compta (Y)

Jean-Christophe Corvol (JC)

Mariana Cosgaya (M)

Nabila Dahodwala (N)

Philippe Damier (P)

Elodie David (E)

Thomas Davis (T)

Marissa Dean (M)

Berengere Debilly (B)

Janell DeGiorgio (J)

Andres Deik (A)

Laure Delaby (L)

Marie-Helene Delfini (MH)

Pascal Derkinderen (P)

Philipp Derost (P)

Maria de Toledo (M)

Lisa Deuel (L)

Ann Marie Diaz-Hernandez (AM)

Cameron Dietiker (C)

Karina Dimenshteyn (K)

Julio Dotor (J)

Franck Durif (F)

Jens Ebentheuer (J)

Karla Maria Eggert (KM)

Sara Eichau Madueño (S)

Claudia Eickoff (C)

Aaron Ellenbogen (A)

Philipp Ellmerer (P)

Ines Esparragosa Vazquez (I)

Alexandre Eusebio (A)

Siobhan Ewert (S)

John Fang (J)

Danielle Feigenbaum (D)

Frederique Fluchere (F)

Alexandra Foubert-Samier (A)

Marie Fournier (M)

Anne Fradet (A)

Valerie Fraix (V)

Samuel Frank (S)

Franka Fries (F)

Monique Gailitzky (M)

Anne Gaille Corbille (A)

Marisol Gallardó Pérez (M)

Jose Manuel Garcia Moreno (JM)

Carmen Gasca (C)

Thomas Gasser (T)

Joyce Gibbons (J)

Caroline Giordana (C)

Alicia Gonzalez Martinez (A)

Ira Goodman (I)

Arantza Gorospe (A)

Marie Goubeaud (M)

David Grabli (D)

Mangone Graziella (M)

Stephan Grimaldi (S)

Jeffrey Gross (J)

Raquel Guimaraes-Costa (R)

Andreas Hartmann (A)

Christian Hartmann (C)

Travis Hassell (T)

Robert Hauser (R)

Antonio Hernandez (A)

Jorge Hernandez-Vara (J)

Günter Höglinger (G)

Christian Homedes (C)

Andrea Horta (A)

Jean-Luc Houeto (JL)

Julius Huebl (J)

Jennifer Hui (J)

Stuart Isaacson (S)

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Annette Janzen (A)

Junior Jauregui (J)

Jocelyne Jiao (J)

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Xavier Joseph (X)

Srinath Kadimi (S)

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Silja Kannenberg (S)

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